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Postnatal exposure of 2,2 ',3,3 ',4,6 '-hexachlorobiphenyI and 2,2 ' 3,4 ' 5 ', 6-hexachlorobiphenyl on sperm function and hormone levels in adult rats
Abstract
Polychlorinated biphenyls (PCBs) are known to affect reproductive system in animals and in accidentally or occupationally exposed humans. Information is lacking on effects of non-dioxin like chlorinated biphenyls (CB) congeners on male reproduction. The aim of this study is to determine whether treatment of postnatal non-dioxin like CB congeners affects sperm function and hormone levels in rats. Male Sprague-Dawley rats received either 2,2',3,3',4,6'-hexachlorobiphenyls (CB 132) or 2,2',3,4',5',6-hexachlorobiphenyls (CB 149) by ip injection of 9.6 or 96 mg/kg at day 21. At 16 weeks, the animals were sacrificed; sperm quality and hormone levels were measured. Body weight, testis and cauda epididymis weights, sperm counts, ROS generation, acrosome reaction rate, serum thyroxine (T(4)), free T(4) and testosterone (TT) concentrations were unaffected. However, treatment of CB 132 and CB 149 caused decreases in sperm motility, curvilinear velocity (VCL), average path velocity (VAP), straight-line velocity (VSL), amplitude of lateral head displacement (ALH) and beat cross frequency (BCF). Serum triiodothyronine (T(3)) level was significantly decreased in CB 132 9.6 mg/kg dose group compared with the controls. On the other hand, a significant decrease was found in free T(3) concentration both in 96 mg/kg of CB 132 and CB 149 groups. In summary, this study showed that CB 132 and CB 149 affects serum levels of triiodothyronine as well as sperm motility, velocity and capability of penetrating oocytes. The mechanism of action and potential effects on human warrant further investigation.
... Many studies have shown that AR 1254 and other PCB compounds cause reproductive damage through histological, spermatological and biochemical changes and damage to the testicular structures (9,11,30,31). Hsu et al. demonstrated that PCBs led to a decrease in motility, concentration and sperm attachment to oocyte and penetration and an increase in abnormal sperm rate (30). Likewise, Erkekoglu P. et al showed that an AR1254 (15 mg/kg) injection resulted in a decrease in epididymal sperm concentrations, sperm motility and testis tissues weight (32). ...
... Many studies have shown that AR 1254 and other PCB compounds cause reproductive damage through histological, spermatological and biochemical changes and damage to the testicular structures (9,11,30,31). Hsu et al. demonstrated that PCBs led to a decrease in motility, concentration and sperm attachment to oocyte and penetration and an increase in abnormal sperm rate (30). Likewise, Erkekoglu P. et al showed that an AR1254 (15 mg/kg) injection resulted in a decrease in epididymal sperm concentrations, sperm motility and testis tissues weight (32). ...
... Caspase 3, a protease that is activated in the early stages of apoptosis, is one of 14 members of the caspase family (39). It is known that PCB 132 and AR1254 administrations increase pro-apoptotic molecules caspase-3 and caspase-9 activities in testicular tissue of rats (13,30,40). Studies have shown that TET initiates apoptosis by inducing caspase-3 activation in tumor cell lines. ...
... The studies were conducted in rats, mice or goats. We identified four studies examining the effects of PCB-77 [39][40][41][42], two studies on those of PCB-118 [43,44], four studies which looked at PCB-126 [39,[45][46][47], two studies for PCB-132 [48,49], one study for PCB-149 [48], two studies reporting on PCB-153 [45,50], two on PCB-169 [51,52] and one report on PCB-180 [53]. All these studies were selected for the data extraction process. ...
... The studies were conducted in rats, mice or goats. We identified four studies examining the effects of PCB-77 [39][40][41][42], two studies on those of PCB-118 [43,44], four studies which looked at PCB-126 [39,[45][46][47], two studies for PCB-132 [48,49], one study for PCB-149 [48], two studies reporting on PCB-153 [45,50], two on PCB-169 [51,52] and one report on PCB-180 [53]. All these studies were selected for the data extraction process. ...
... Both studies we identified for PCB-132 were conducted in rats [48,49] and were evaluated as "definitely low" or "probably low risk" in the key elements but had some other elements rated lower and were therefore considered to be of Medium confidence (TIER 2). Both studies used i.p. injection of PCB-132 and reported declines in semen quality. ...
Background
Mixture risk assessments require reference doses for common health endpoints of all the chemicals to be considered together. In support of a mixture risk assessment for male reproductive health, we conducted a systematic review of the literature on associations between exposures to Polychlorinated Biphenyls (PCBs) and declines in semen quality. PCBs can act as Aryl-hydrocarbon Receptor (AhR)-agonists and Androgen Receptor (AR)-antagonists, both mechanisms which can affect sperm parameters. PCBs and other AR-antagonists can produce additive combination effects. Based on these observations our objective was to systematically gather data from animal and human studies to derive a reference dose for declines in semen quality for individual PCB.
Methods
We systematically reviewed and evaluated the evidence in human epidemiological and experimental animal studies on associations between PCBs and deteriorations in semen quality. Human data and findings from animal studies with PCB mixtures were considered as supporting evidence. Information for individual congeners from animal studies was required for inclusion in mixture risk assessment. Using a robust confidence rating approach, we identified suitable studies to derive reference doses for individual PCB congeners.
Results
Evaluation of human epidemiological studies revealed several reports of adverse effects on sperm parameters linked to PCB exposures, although some studies reported improved semen quality. Our review of experimental animal studies found that treatments with PCBs affected semen quality, in most cases adversely. We found robust evidence that PCB-118 and -169 were linked to declines in semen quality. Evidence for adverse effects of PCB-126, -132, -149, and -153 was moderate, whereas for PCB-77 it was slight and for PCB-180 indeterminate. Using widely accepted risk assessment procedures, we estimated reference dose values of 0.0029 µg/kg/day for PCB-118 and 0.00533 µg/kg/day for PCB-169. In addition, we derived values for PCB-126: 0.000073 µg/kg/day, PCB-132: 0.0228 µg/kg/day, PCB-149: 0.656 µg/kg/day, and PCB-153: 0.0058 µg/kg/day.
Conclusions
We found robust evidence for links between PCB exposure and deteriorations in semen quality, and derived reference doses for a set of congeners. We intend to use these values in combination with congener-specific exposure data in a mixture risk assessment for declines in semen quality, involving several other antiandrogenic chemicals.
... PCB-132: Both studies we identi ed for PCB-132 were conducted in rats (Hsu et al. 2007(Hsu et al. , 2003 and were evaluated as "de nitely low" or "probably low risk" in the key elements but had some other elements rated lower and were therefore considered to be of Medium con dence (TIER 2). Both studies used i.p. injection of PCB-132 and reported declines in semen quality. ...
... Both studies used i.p. injection of PCB-132 and reported declines in semen quality. One study was conducted in juvenile rats and determined a LOAEL of 9.6 mg/kg/d (Hsu et al. 2003) whereas the second studied prenatal exposure to PCB-132 (LOAEL = 1 mg/kg/d) (Hsu et al. 2007). Both studies were considered for derivation of a reference dose. ...
... PCB-149: The only available study on PCB-149 was evaluated as "de nitely low" or "probably low risk" in the key elements but had other elements rated lower and was assigned to TIER 2 (Medium con dence) (Hsu et al. 2003). This study was conducted in juvenile rats, used i.p. injection of PCB-149 and estimated a NOAEL of 9.6 mg/kg/d which was used to derive a reference dose. ...
Background: Mixture risk assessments require reference doses for common health endpoints of all the chemicals to be considered together. In support of a mixture risk assessment for male reproductive health, we conducted a systematic review of the literature on associations between exposures to Polychlorinated Biphenyls (PCBs) and declines in semen quality. PCBs can act as Aryl-hydrocarbon receptor (AhR)-agonists and androgen receptor (AR)-antagonists, both mechanisms which can affect sperm parameters. PCBs and other AR-antagonists can produce additive combination effects. Based on these observations our objective was to derive a reference dose for declines in semen quality for individual PCB congeners for use in a mixture risk assessment.
Methods: We systematically reviewed and evaluated the evidence in human epidemiological and experimental animal studies on associations between PCBs and deteriorations in semen quality. Human data and findings from animal studies with PCB mixtures were considered as supporting evidence. Information for individual congeners from animal studies was required for inclusion in mixture risk assessment. Using a robust confidence rating approach, we identified suitable studies to derive reference doses for individual PCB congeners.
Results: Evaluation of human epidemiological studies revealed several reports of adverse effects on sperm parameters linked to PCB exposures, although some studies reported improved semen quality. Our review of experimental animal studies found that treatments with PCBs affected semen quality, in most cases adversely. We found robust evidence that PCB-118 and -169 were linked to declines in semen quality. Evidence for adverse effects of PCB-126, -132, -149, and -153 was moderate, whereas for PCB-77 it was slight and for PCB-180 indeterminate. Using widely accepted risk assessment procedures, we estimated reference dose values of 0.0029 µg/kg/day for PCB-118 and 0.00533 µg/kg/day for PCB-169. In addition, we derived values for PCB-126: 0.000073 µg/kg/day, PCB-132: 0.0228 µg/kg/day, PCB-149: 0.656 µg/kg/day, and PCB-153: 0.0058 µg/kg/day.
Conclusions: We found robust evidence for links between PCB exposure and deteriorations in semen quality, and derived reference doses for a set of congeners. We intend to use these values in combination with congener-specific exposure data in a mixture risk assessment for declines in semen quality, involving several other anti-androgenic chemicals.
... Sperm collected from males exposed prenatally to PCBs and PCDFs from consumption of contaminated rice oil in Yucheng, Taiwan, between 1978 and1979 were characterized by abnormal morphology, reduced motility, and reduced capacity to penetrate hamster oocytes . A higher percentage of oligospermia, abnormal sperm morphology, and reduced sperm-binding capability and penetration has been reported in this same cohort (Hsu et al., 2003b). Decreases in sperm concentration and sperm motility and total sperm count were reported in males exposed to TCDD in Belgium (Comhaire et al., 2007). ...
... A single dose (9.6 or 96 mg/kg body weight) of 2,2 0 ,3,3 0 ,4,6 0 -hexachlorobiphenyl (PCB 132) or 2,2 0 ,3,4 0 ,5 0 ,6hexachlorobiphenyl (PCB 149) at 21 days of age resulted in decreased sperm motility, velocity, and the ability of sperm to penetrate oocytes (Hsu et al., 2003a(Hsu et al., , 2003b. Prenatal exposure to PCB 132 (1 or 10 mg/kg body weight) resulted in a decrease in cauda epididymal weight, epididymal sperm count, and motile epididymal sperm count in adult offspring (Hsu et al., 2007). ...
Polychlorinated biphenyls (PCBs), polybrominated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans belong to a group of compounds that are structurally related and are environmentally and biologically persistent. These chemicals have a tendency to bioaccumulate and biomagnify in the food chain. Residues of these chemicals have been detected in remote areas of the world and in a variety of animal species, including humans. Exposure to these chemicals has been linked to a broad spectrum of effects. Fetal and early developmental exposures are particularly sensitive and can have more profound and irreversible outcomes when compared to adult exposure. Latent effects of early exposures include, but are not limited to, depressed circulating thyroid hormone levels and abnormal thyroid cytology; developmental effects of the heart, palate, and kidney; delayed cognitive development; altered sensory and motor abilities; and reproductive impairment and compromised neuronal function. Although AhR activation has been attributed to several dioxin-like coplanar compounds, some PCBs that are noncoplanar in nature seem to exert their toxic effects through different mechanisms including calcium signaling, oxidative stress, thyroid hormone perturbations, and neurotransmitter imbalance. While certain congeners and isomers can pose a very serious threat to the health of animals and humans, environmental exposure situations are generally such that risks of health effects are generally low. The most significant problem by these compounds involved in accidental poisoning via food supply or consumption of contaminated food from contaminated areas. Additionally, there are areas of the environment that are heavily contaminated by these chemicals because of past industrial activities. Animals and humans residing in or near contaminated locations certainly are at risk of serious health effects. Efforts must continue to reduce exposure to protect wildlife and humans. The best way to accomplish is to modernize technological processes to prevent the release of these chemicals into the environment.
... Animal studies corroborate the findings of reduced sperm motility after PCB exposure. In 2 sequential studies, Hsu et al 36,37 demonstrated that both CB-132 and CB-149 (not dioxin-like) and the dioxin-like CB-77 reduced adult rat sperm motility after a single intraperitoneal injection of a minimum of 9.6 mg/kg at day 21 after birth. Human sperm exposed in vitro to PCBs are generally not affected by exposure to concentrations several orders of magnitude higher than those found in semen samples. ...
... 37 This finding indicates that premature acrosome reaction may be an underlying mechanism of impaired sperm motility. 36 Another mechanism of action of motility impairment may be through reduction of prostate specific antigen (PSA) in semen, which has previously been demonstrated to be associated with sperm motility. 29 Recent limited evidence of PSA disturbances after CB-153 exposure were found in the Swedish fishermen included in the present study. ...
Inconsistent results have been found in previous human studies on male reproductive toxicity of persistent organochlorine pollutants. The majority of studies have been conducted among selected populations of infertility clients or among occupational cohorts including a limited number of participants.
We conducted a cross-sectional study of semen quality and serum concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) among 763 men. We included men from all regions in Greenland (n = 194), fishermen from Sweden (n = 185), inhabitants of the city of Kharkiv, Ukraine (n = 195), and inhabitants of the city of Warsaw, Poland (n = 189). Blood samples were analyzed for CB-153 and p,p'-DDE using gas chromatography-mass spectrometry and adjusted for serum lipids.
Sperm concentration was not impaired with increasing serum CB-153 or p,p'-DDE levels in any of the separate groups or overall. Similarly, the proportion of morphologically normal sperm was not associated with either CB-153 or p,p'-DDE blood concentration. However, sperm motility was inversely related to CB-153 concentration in Greenland and the Swedish fishermen population. Across all 4 regions, the sperm motility decreased on average by 3.6% (95% confidence interval = 1.7% to 5.6%) per one-unit increase in the log of blood CB-153 (ng/g lipid). The concentration of p,p'-DDE was negatively associated with sperm motility in the Greenlandic population and in the compiled dataset.
Adult exposure to persistent organochlorine pollutants within the ranges observed in the present study is not likely to cause reduction in sperm concentration or morphology. However, higher exposure may be associated with impaired sperm motility.
... There is limited evidence that 2,3,6-substituted chlorinated biphenyls (CB) congeners may possess certain toxicities that have not previously been identified. We have demonstrated that postnatal exposure to PCB 132 affects serum triiodothyronine (T 3 ) levels, and sperm motility, velocity and capability of penetrating oocytes in rats (Hsu et al., 2003b). Although these data are suggestive of probable toxicity to sperm function, it is not clear whether prenatal exposure to PCB 132 affects postnatal testicular and sperm function, and if so, by what mechanisms. ...
... and sperm functions are not well documented in animal and human studies. In our previous study, a single dose of 9.6 mg/kg of PCB 132 at PND 21 in male rats decreased serum total T 3 level and SOPR at PND 112; a single dose of 96 mg/kg significantly decreased sperm motility, velocity, SOPR, and serum-free T 3 (Hsu et al., 2003b). In the present study, prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased average cauda epididymal weight, epididymal sperm count, and motile epididymal sperm count in adult offspring. ...
Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification.
... The two most recent studies carried out in Mexico and South Africa enrolled men with high environmental exposures and both demonstrated strong associations between serum concentrations of p,p´-DDE and various measures of sperm motility. Additional supportive evidence comes from two adult rat studies reporting reduced sperm motility after treatment with high doses of coplanar as well as noncoplanar PCBs (Hsu et al. 2003(Hsu et al. , 2004. Interestingly, the non-coplanar PCB congeners (CB-132 and CB-149) only affected sperm motility, whereas the coplanar dioxin-like PCB congener CB-77 also reduced sperm counts. ...
... There are several earlier human studies on the effects of postnatal POP exposure on testicular function. In the study with subjects with the highest exposure to PCBs and polychlorinated dibenzo-p-dioxins after the Yucheng accident in Taiwan, abnormal sperm morphology and reduced sperm capacity to penetrate hamster eggs were found (Hsu et al. 2003). Two recent large cross-sectional studies of men with high environmental exposure to DDT in Mexico Bonde et al. 274 VOLUME 116 | NUMBER 3 | March 2008 • Environmental Health Perspectives Table 3. Adjusted geometric mean values and linear regression coefficients of male reproductive hormones in serum, semen characteristics, and markers of epididymal and accessory sex gland function by categories of p,p´-DDE. ...
We synthesized the main findings from an international epidemiologic study on the impact of biopersistent organic pollutants (POPs) on human reproductive function.
We used a database with interview and biological data from 2,269 women and their spouses, and 18 published core papers.
The study did not provide direct evidence of hormone-like activity of the polychlorinated biphenyl (PCB) congener CB-153 and the main dichlorodiphenyltrichloroethane (DDT) metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), as serum concentrations of these compounds were not consistently related to either endogenous or exogenous hormone activity in serum. Nevertheless several links bewteen POP exposure and biomarkers of male reproductive function were identified. First, an association between high CB-153 serum levels and low sperm counts was detected within a subgroup of men with short androgen receptor CAG repeat length. Second, a relationship between increased CB-153 serum concentrations and decreased sperm motility was seen in all four studied regions, and indications of reduced neutral alpha-glucosidase activity in seminal plasma point to a post-testicular effect. Third, damage of sperm chromatin integrity was considerably less frequent in Greenlandic Inuits compared with that in European groups, and only in the latter was impairment of sperm chromatin integrity related to POPs. Despite these effects, fertility in terms of time taken to conceive was not related to POPs except in Inuits. A likely explanation of the latter was not identified.
POPs may interfere with male reproductive function without major impact on fertility. The data do not provide direct evidence for endocrine disruption, hence other mechanisms should also be considered.
... Earlier studies indicate that PCB increased apoptosis in Leydig cells (Oskam et al., 2004), testicular and prostate weight and abnormal sperm count (Faqi et al., 1998), caused degenerative changes in seminiferous tubules (Alston et al., 2003), decreased sperm motility (Hsu et al., 2003, Krishnamoorthy et al., 2007 and sperm production (Faqi et al., 1998). Lu et al. (2014) suggested that nonylphenol administration at doses of 100 and 250 mg/kg by oral gavage for 90 days in male rats caused tubular atrophy in the testes, and decreased epididymal SOD, and CAT activities, serum testosterone level, sperm count and motility in cauda epididymis. ...
... Acrylamide is mostly related to fried or baked starch rich products in which also cereulide production is predominantly reported(Agata et al., 2002;Toh et al., 2004). Polychlorinated biphenyls (PCBs) are reported to affect the reproductive system in animals and in exposed humans(Hsu et al., 2003). While chronic effect was reported, the acute effect of PCBs and non-dioxin like CBs was not evident. ...
... PCBs are globally ubiquitous contaminants known to bioaccumulate and exert a variety of harmful effects on organisms [57]. The detrimental effects of PCBs on reproduction are well documented in a number of vertebrates [313][314][315] including fish [75,77,78,225,[316][317][318]. Effects of PCBs on fish reproduction include altered hormone levels [319], reduced fecundity [320], decreased hatching success [319], decreased gonad size [203,321], and lower offspring survival [264,318,319]. ...
Cytochrome P4501A (CYP1A), a xenobiotic metabolizing enzyme found in allvertebrates, is highly induced following exposure to a number of organic contaminants.Several populations of teleosts residing in highly contaminated areas have been found toexhibit resistance to the toxic effects of contaminants, a condition characterized byreduced expression of CYP1A.Within this work I demonstrated that expression of CYP1A mRNA, protein, andactivity in caged rainbow trout (Oncorhynchus mykiss) was an effective biomarker ofpolychlorinated biphenyl (PCB) contamination. Furthermore, through the use of bothlaboratory and field studies, I demonstrated that several species inhabiting a PCBcontaminated site exhibited either acquired (Ameiurus natalis) or natural (Lepomiscyanellus) resistance to the CYP1A inducing effects of PCBs. Further studiescharacterized the response of several other Lepomis species to CYP1A inducingcompounds, demonstrating that the natural resistance of L. cynaellus is a characteristicshared by at least two other members of the genus. Lepomis species were relativelyinsensitive to CYP1A induction following PCB exposure yet exhibited highly inducedCYP1A levels following exposure to another CYP1A inducer, the model polyaromatichydrocarbon benzo[a]pyrene (BaP), suggesting a number of species within the genusLepomis may display natural resistance to certain classes of CYP1A inducingcompounds.Additional studies using responsive and resistant populations of killifish wereused to examine the consequences of resistance on fish physiology. Thyroid hormones,known to be altered by PCBs in mammals, were variable but did not differ significantlybetween responsive and resistant fish following PCB exposure. Treatment with PCBssuppressed production of the egg yolk precursor protein vitellogenin in primaryhepatocytes of responsive fish. Studies examining the developmental impacts of toxicantexposure demonstrated altered aspects of development in PCB responsive but notresistant Fundulus heteroclitus embryos exposed to polybrominated diphenyl ethers(PBDEs), compounds structurally related to PCBs. PBDE exposure in juvenile Ictaluruspunctatus failed to induce CYP1A or uridine diphosphate glucuronyltransferase(UDPGT) activity indicating PBDEs do not impact these commonly measuredtoxicological endpoints. The findings of this work describe novel pollutant responses in anumber of species with varying degrees of pollutant sensitivity and contribute to theunderstanding of toxicant induced alterations in teleost physiology.
... For example, single subcutaneous injection (18, or 60 mg/kg b.w.) of planar PCB 77 reduced daily sperm production and increased percentage of abnormal sperm in adult male rats (Faqi et al., 1998). Postnatal exposure to single dose (9.6, or 96 mg/kg b.w.) of nonplanar PCB 132 and PCB 149, caused decreases in sperm motility, velocity and capability of penetrating oocytes in adult rats with no change in serum testosterone concentration (Hsu et al., 2003). The 5-20-month-old bulls kept in area contaminated accidentally by PCBs from paint coats showed the presence of PCBs in the tissues (3.7-12.6 mg PCBs/kg of muscle fat), and decreased activity of testicular mitochondrial steroidogenic enzyme CYP11A (Machala et al., 1998). ...
The mechanism by which Aroclors and other polychlorinated biphenyls (PCBs) inhibit testicular androgenesis in vivo and in vitro has not been characterized. Here we studied in adult rats the effects of intratesticular (i.t.t.), intraperitoneal (i.p.) and by gavage (p.o.) administration of Pyralene, an Aroclor 1260-based transformer fluid, on testicular androgenesis and oxidative status in androgen-producing interstitial cells and liver. Pyralene markedly decreased in vitro agonist stimulated androgenesis 24 h after bilateral i.t.t.-injection (25 microg/testis), 24 h and 96 h after single i.p.-injection (10 and 50 mg/kg body weight), and 96 h after p.o.-administration (7x10 mg and 7x50 mg/kg body weight daily). Inhibited androgenesis was accompanied by changes in the activity of antioxidant enzymes (AOEs) in interstitial cells after local i.t.t.-treatment and occasionally after systemic Pyralene application. Among changes in the activity, glutathione peroxidase and catalase reflected relatively well the toxicity of Pyralene in these cells. In liver, glutathione-S-transferase (GST) and glutathione peroxidase activities were enhanced after p.o.-treatment and total glutathione (tGSH) content and lipid peroxidation (LP) were enhanced after i.p.-administration. These results indicate that Pyralene inhibits androgenesis independently of the method of its administration. The results also suggest that changes in the oxidative status in testicular milieu are not critical for Pyralene-induced inhibition of androgenesis.
... In contrast to the findings for sperm concentration, no threshold value was found for the relationship between percentage motile sperm and fertility, indicating that any factors affecting sperm motility can also have an effect on the fertility potential of the male. There is evidence from wildlife and laboratory animal studies that POPs can affect male reproductive function, mainly if the exposure takes place during fetal or early postnatal life (Sager, 1983;Sager et al., 1987;Mably et al., 1992b;Fry, 1995;Gray et al., 1995Gray et al., , 1997Kelce et al., 1995;Cooke et al., 1996;Sommer et al., 1996;Faqi et al., 1998;Huang et al., 1998;Kim, 2001;Hsu et al., 2003b). There are only few reports on the effects of POPs on male reproduction in humans, mainly indicating weak negative effects on sperm motility (Bush et al., 1986;Guo et al., 2000;Dallinga et al., 2002;Hauser et al., 2003;Hsu et al., 2003a;Richthoff et al., 2003). ...
During the last decades, there has been concern that exposure to endocrine disruptors, such as persistent organochlorine pollutants (POPs), may contribute to an impairment of male reproductive function. To investigate whether exposure to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) affects semen quantity and quality and reproductive hormones, 195 Swedish fishermen, aged 24-65 years, were investigated.
The men provided semen samples which were analysed in a mobile laboratory unit. Blood samples and information relating to lifestyle, medical and reproductive history were obtained.
The subjects had a median CB-153 serum level of 193 ng/g lipid (range 39-1460) and a median p,p'-DDE serum level of 240 ng/g lipid (range 334-2251). When CB-153 was categorized into quintiles, the subjects in the quintile with the highest concentration (> 328 ng/g lipid), tended to have decreased sperm motility compared with the subjects in the lowest quintile (< 113 ng/g lipid). The age-adjusted mean difference was 9.9% (95% confidence interval -1.0 to 21% P = 0.08). We found no significant associations between p,p'-DDE and semen characteristics or reproductive hormones.
The association between CB-153 and sperm motility, although not formally significant, is of interest considering the possible endocrine-disrupting effects of polychlorinated biphenyls (PCBs).
... The OC contamination may also induce an enhanced catabolism and biliary excretion of vitamin A and thyroid hormones (Zile, 1992;Brouwer et al., 1998;Rolland, 2000). The stronger relationship between PCBs and T3 as compared to T4 has already been reported in several other studies with terrestrial and marine mammals (Osius et al., 1999;Chiba et al., 2001;Hagmar et al., 2001;Hsu et al., 2003;Braathen et al., 2004). A disruption of peripheral T4 deiodination activity could be responsible for this phenomenon (Osius et al., 1999). ...
Top-trophic predators like California sea lions bioaccumulate high levels of persistent fat-soluble pollutants that may provoke physiological impairments such as endocrine or vitamins A and E disruption. We measured circulating levels of polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) in 12 healthy juvenile California sea lions captured on Año Nuevo Island, California, in 2002. We investigated the relationship between the contamination by PCBs and DDT and the circulating levels of vitamins A and E and thyroid hormones (thyroxine, T4 and triiodothyronine, T3). Serum concentrations of total PCBs (sigmaPCBs) and total DDT were 14 +/- 9 mg/kg and 28 +/- 19 mg/kg lipid weight, respectively. PCB toxic equivalents (sigmaPCB TEQs) were 320 +/- 170 ng/kg lipid weight. Concentrations of sigmaPCBs and sigmaPCB TEQs in serum lipids were negatively correlated (p < 0.05) with serum vitamin A and T3, potentially reflecting PCB-related toxicity. A slight but not significant negative correlation (p < 0.1) was observed between serum T4 and the levels of sigmaPCBs and sigmaPCB TEQs. Conversely, no relationship was evident between the contaminant concentrations and vitamin E (p > 0.1). As juvenile California sea lions are useful sentinels of coastal contamination, the high levels encountered in their serum is cause for concern about the ecosystem health of the area.
... In experimental animals dioxin-like chemicals, including some PCBs, cause reproductive toxicity (Birnbaum and Tuomisto 2000; Peterson et al. 1993; Petroff et al. 2001). For example, administration of heavily chlorinated, noncoplanar PCB congeners to male rats decreases several markers of sperm function (Hsu et al. 2003). Exposure of female mice to the coplanar congener 3,3´,4,4´-tetrachloro- biphenyl decreases reproductive capacity (Huang et al. 1998a ), and exposure of pregnant mice to Aroclor 1242 or to 3,3´,4,4´- tetrachlorobiphenyl alters fertility in male offspring (Fielden et al. 2001; Huang et al. 1998b). ...
The effectiveness of bioremediation efforts is assessed traditionally from the loss of the chemical of interest. In some cases, analytical techniques are coupled with evaluation of toxicity to organisms representative of those found in the affected environment or surrogate organisms. Little is known, however, about the effect of remediation of environmental chemicals on potential toxicity to mammalian organisms. We discuss both an approach that employs mammalian cell system bioassays and the criteria for selection of the assays. This approach has been used to evaluate the biological response to mixtures of polychlorinated biphenyls (PCBs) before and after remediation by reductive dechlorination. The dechlorination process used results in accumulation of congeners substituted in only the ortho and para positions and containing fewer chlorines than the starting mixtures. Evaluation of the dechlorinated mixture reveals a loss of biological activity that could be ascribed to coplanar PCBs not containing chlorine in the ortho positions. Conversely, biological activity associated with ortho-substituted PCB congeners is unaffected or increased by remediation. Thus, the results of the bioassays are consistent with the remediation-induced change in the profile of PCB congeners and the known mechanisms of action of PCBs. The results emphasize a need for evaluation of the products of remediation for biological activity in mammalian systems. Furthermore, the approach outlined demonstrates the potential to assess the impact of remediation on a range of biological activities in mammalian cells and thus to estimate positive and negative effects of remediation strategies on toxicity. Future needs in this area of research include assays to evaluate biological effects under conditions of exposure that mimic those found in the environment and models to extrapolate effects to assess risk to people and wildlife.
... The etiology of the malignancies is unknown, but biological plausibility and experimental evidence support the hypothesis that environmental pollutants are acting as endocrine-active compounds. For example, in rodents, reduced sperm counts have been observed at adulthood when animals were pre-and/or postnatally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (Faqi et al. 1998b;Theobald and Peterson 1997), PCBs (Faqi et al. 1998a;Hsu et al. 2003;Kuriyama and Chahoud 2004), and the pesticides deltamethrin (Andrade et al. 2002) and lindane (Dalsenter et al. 1997). Nevertheless, there is scant information regarding possible effects of PBDEs on male reproduction. ...
In utero exposure to a single low dose of 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE-99) disrupts neurobehavioral development and causes permanent effects on the rat male reproductive system apparent in adulthood. PBDEs, a class of flame retardants, are widely used in every sector of modern life to prevent fire. They are persistent in the environment, and increasing levels of PBDEs have been found in biota and human breast milk. In the present study we assessed the effects of developmental exposure to one of the most persistent PBDE congeners (PBDE-99) on juvenile basal motor activity levels and adult male reproductive health. Wistar rat dams were treated by gavage on gestation day 6 with a single low dose of 60 or 300 microg PBDE-99/kg body weight (bw). In offspring, basal locomotor activity was evaluated on postnatal days 36 and 71, and reproductive performance was assessed in males at adulthood. The exposure to low-dose PBDE-99 during development caused hyperactivity in the offspring at both time points and permanently impaired spermatogenesis by the means of reduced sperm and spermatid counts. The doses used in this study (60 and 300 microg/kg bw) are relevant to human exposure levels, being approximately 6 and 29 times, respectively, higher than the highest level reported in human breast adipose tissue. This is the lowest dose of PBDE reported to date to have an in vivo toxic effect in rodents and supports the premise that low-dose studies should be encouraged for hazard identification of persistent environmental pollutants.
... Several studies on wildlife and laboratory animals have shown that exposure to PCBs and p,p´-DDE is capable of interfering with reproductive and endocrine functions (Cooke et al. 1996; Faqi et al. 1998; Fry 1995; Guillette et al. 1994, 1996; Hsu et al. 2003b; Kim 2001). ...
Persistent organochlorine pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (p,p'-DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), are stable lipophilic compounds widely found in the environment and in the general population. They can enter the food chain, and their negative impact on male reproduction is currently under active scrutiny. To explore the hypothesis that environmental exposure to these compounds is associated with altered sperm chromatin structure integrity in human sperm, we conducted a study of 176 Swedish fishermen (with low and high consumption of fatty fish, a very important exposure source of POPs). We determined serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and p,p'-DDE, and we used the sperm chromatin structure assay (SCSA) to assess sperm DNA/chromatin integrity. When CB-153 serum levels (individual dose range, 39-1,460 ng/g lipid) were categorized into equally sized quintiles, we found an association with the DNA fragmentation index (%DFI). A significantly lower %DFI was found in the lowest CB-153 quintile (< 113 ng/g lipid) compared with the other quintiles; there was a similar tendency, although not statistically significant, between %DFI and p,p'-DDE. These results suggest that POP exposure may have a slight negative impact on human sperm chromatin integrity.
... Acrylamide is mostly related to fried or baked starch rich products in which also cereulide production is predominantly reported (Agata et al., 2002;Toh et al., 2004). Polychlorinated biphenyls (PCBs) are reported to affect the reproductive system in animals and in exposed humans (Hsu et al., 2003). While chronic effect was reported, the acute effect of PCBs and nondioxin like CBs was not evident. ...
Computer Aided Semen Analysis (CASA) study of the boar semen motility has been demonstrated to be an appropriate assay for detection of cereulide (Bacillus cereus emetic toxin). Application of the boar semen bio-assay to detect cereulide directly in foods requires investigation of potential interference of food components, preservatives and other microbial and chemical food contaminants with the bio-assay. Current study provides evidence that none of included Staphylococcus aureus enterotoxins A, B, C and D nor B. cereus Hemolysin BL (HBL) and non-hemolytic enterotoxin (NHE) and three mycotoxins (Sterigmatocystin, Fumonisin B1 and Patulin) exhibited a toxic impact on semen progressive motility. Aflatoxin M1, M3 and zearalenone impaired semen motility only at concentrations (0.004 mg ml− 1, 0.1 mg ml− 1 and 10 mg ml− 1, respectively) much higher than those found in foods and those permitted by legislation, in comparison to cereulide which induces motility cease at concentrations lower than 20 ng ml− 1. Ten commonly used preservatives, namely potassium sorbate, sodium benzoate, (dl) malic acid, citric acid, (l+) tartaric acid, acetic acid, (dl) lactic acid, (l+) ascorbic acid, sodium chloride and sucrose induced no cease in spermatozoa motility even at preservative concentrations higher than permitted by legislation. Dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and acrylamide had no acute effect on spermatozoa motility at concentrations of 500 and 10,000 mg ml− 1, respectively.
Exposure to toxic chemicals, such as plasticizers, alkylphenol compounds, and polychlorinated biphenyls (PCBs), has increased due to environmental contamination. PCBs, categorized as persistent organic pollutants (POPs), are lipophilic chemicals commonly used in lubricants, cutting oils, and electrical insulators. PCBs may have detrimental effects on hormone-producing glands, potentially contributing to male infertility. Thus, the objective of this study was to provide a comprehensive overview of the adverse effects of PCBs on the male reproductive system. Searches of three electronic databases were performed using MESH terms and 32 studies were included. Although the exact mechanism of action for PCBs remains unclear, several PCBs are regarded as potential endocrine disruptors due to their ability to interact with hormone signaling pathways. PCBs have been found to disrupt physiological functions by mimicking endogenous hormones as agonists or antagonists, altering patterns of hormone synthesis, hormone receptor affinities or numbers, and modulating enzymes involved in hormone secretion. These reports highlight the pleiotropic nature of PCB function and the susceptibility of the reproductive system. Endocrine-disrupting PCBs can mimic, alter, or block hormonal responses, inhibiting natural signaling to the testes and epididymis via various mechanisms such as binding to sex hormone-binding globulin and androgen-binding protein or blocking cell surface receptors. Furthermore, PCBs can alter the hormonal environment in the prostate or seminal vesicles by changing the affinity of androgens for their receptors. The testicles and genital organs may be susceptible to various estrogenic effects, leading to changes in the quality or quantity of their secretions and the volume of semen.
Polychlorinated biphenyls (PCBs), polybrominated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans belong to a group of compounds that are structurally related and are environmentally and biologically persistent. These chemicals are ubiquitous and detectable in a variety of environmental media and biota. Exposure to these chemicals has been linked to a broad spectrum of effects. Fetal and early developmental exposures are particularly sensitive and can have different outcomes when compared to exposure in adults. Latent effects of early exposures include, but are not limited to, depressed circulating thyroid hormone levels and abnormal thyroid cytology; developmental effects of the heart, palate, and kidney; delayed cognitive development; altered sensory and motor abilities; and reproductive impairment and compromised neuronal function. Although AhR activation has been attributed to several dioxin-like coplanar compounds, some PCBs that are noncoplanar in nature seem to exert their toxic effects through different mechanisms, including calcium signaling, oxidative stress, thyroid hormone perturbations, and neurotransmitter imbalance. The most significant problem caused by these compounds involve accidental poisoning via food supply or consumption of contaminated food from contaminated areas. Additionally, there are areas of the environment that are heavily contaminated by these chemicals because of past industrial activities. Animals and humans residing in or near contaminated locations certainly are at risk of serious health effects. Efforts must continue to reduce exposure to protect wildlife and humans. The best way to accomplish is to modernize technological processes to prevent the release of these chemicals into the environment.
This chapter discusses the chemical pollutants present in the environment which affect the health of animals and humans. Polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), polychlorinated dibenzo-. p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) form a large group of compounds, the polyhalogenated aromatic hydrocarbons or PHAHs, which are structurally related and are environmentally and biologically persistent. Polybrominated biphenyls were manufactured for use as flame retardants in industrial and consumer products. The release of PCBs into the environment primarily has been the result of leaks, spills and improper disposal. Animals and humans residing in or near contaminated locations certainly are at risk of serious health effects. In those situations, efforts must continue to eliminate or reduce exposure to these very persistent and toxic chemicals. The AhR is a ligand-activated transcription factor that is involved in the regulation of a number of genes, including those for enzymes that play a role in the metabolism of xenobiotics as well as genes involved in cell growth regulation and differentiation. Exposure to 2,3,7,8-TCDD during pregnancy causes prenatal mortality in the mouse, rat, guinea pig, hamster, rabbit, mink and monkey. Similarly in humans, exposure to these chemicals can impair cognitive functions, motor development as well as gender-related behavior and also contribute to the prevalence of attention deficit hyperactivity disorder and affect the female reproductive organs in a big way. The developing cardiovascular system is a sensitive target of many environmental pollutants in humans as well as wildlife.
The mechanism by which Aroclors and other polychlorinated biphenyls (PCBs) inhibit testicular androgenesis in vivo and in vitro has not been characterized. Here we studied in adult rats the effects of intratesticular ( itt ), intraperitoneal ( ip ) and by gavage ( po ) administration of Pyralene, an Aroclor 1260-based transformer fluid, on testicular androgenesis and oxidative status in androgen-producing interstitial cells and liver. Pyralene markedly decreased in vitro agonist stimulated androgenesis 24 h after bilateral itt -injection (25 μg/testis), 24 h and 96 h after single ip -injection (10 and 50 mg/kg body weight), and 96 h after po -administration (7×10 mg and 7×50 mg/kg body weight daily). Inhibited androgenesis was accompanied by changes in the activity of antioxidant enzymes (AOEs) in interstitial cells after local itt -treatment and occasionally after systemic Pyralene application. Among changes in the activity, glutathione peroxidase and catalase reflected relatively well the toxicity of Pyralene in these cells. In liver, glutathione- S -transferase (GST) and glutathione peroxidase activities were enhanced after po -treatment and total glutathione (tGSH) content and lipid peroxidation (LP) were enhanced after ip -administration. These results indicate that Pyralene inhibits androgenesis independently of the method of its administration. The results also suggest that changes in the oxidative status in testicular milieu are not critical for Pyralene-induced inhibition of androgenesis.
A new sorbent material, calcium fluoride-acid red 138 (AR138), was synthesized and characterized by various methods. The hybrid adsorbent for adsorption of PCBs corresponded to the octanol–water partition law, and their partition coefficients were calculated to be 5,836.8 mg kg−1 for PCB029, 8,311.9 mg kg−1 for PCB101, and 20,815 mg kg−1 for PCB180, respectively. When the hybrid adsorbent was used in the treatment of a polluted ground water sample, the removal of PCB concentrations was satisfactory. All the reactants used in the synthesis of the adsorbent material are easily available and are harmless to the environment. Also, the AR138 reactant may reuse a concentrated AR138-producing wastewater instead. Therefore, this work has developed a simple, eco-friendly, and “waste treat waste” method for the large-scale production of a cost-effective sorbent.
A new kind of milli-sized sorbent—calciumalginate supporting a weak acidic pink red B (APRB)–calcium fluoride nano-sized hybrid—was prepared. The micro-structure of the hybrid and adsorbent were characterized, and its adsorption capacity for organic contaminants, e.g. dyes, PCBs and microcystin (MC)-LR, was investigated. Cationic dyes were adsorbed selectively via charge attraction, with a saturation capacity of 188 mg of cationic red 3R per gram of the milli-sized adsorbent. However, the adsorptions of PCBs and MC-LR corresponded to the octanol–water partition law, and their partition coefficients were calculated to be 7788.6 mg kg−1 for PCB029, 13325 mg kg−1 for PCB101, 434.6 mg kg−1 for PCB180, and 369.2 mg kg−1 for MC-LR. When the milli-sized adsorbent was used in the treatment of two concentrated dye wastewaters and two polluted ground waters, the removal of the colored substances, chemical oxygen demand (COD), and concentration of PCBs and MC-LR were satisfactory. In the synthesis of the materials, all of the reactants are easily available and harmless to the environment, and APRB may be obtained from concentrated APRB-containing wastewater instead. The development of the milli-sized hybrid adsorbent provided liquid–solid separation, for favorable use in engineering. It will play an important role in the treatment of concentrated wastewater and the remediation of ground water contamination.
The present study was conducted to investigate the possible protective effects of lycopene (LP) and ellagic acid (EA) on aroclor (AR) 1254-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. The control group was treated with placebo. LP (10 mg/kg/every other day), EA (2 mg/kg/every other day) and AR (2 mg/kg/day) groups were given alone LP, EA and AR respectively. One of the last two groups received AR + LP, and the other treated with AR + EA. Body and reproductive organ weights, epididymal sperm characteristics, testicular tissue lipid peroxidation levels, antioxidant enzyme activities, histopathological changes and apoptosis via Bax and Bcl-2 genes were investigated. AR administration caused statistically significant decreases in body-weight, epididymal sperm concentration, testicular superoxide dismutase activity, diameters of seminiferous tubules, germinal cell layer thickness and Johnsen's testicular score, and increases in relative weights of testis, epidydimis and seminal vesicles, rates of abnormal sperm and apoptotic cell expression along with degeneration, desquamation and disorganization in spermatogenic cells, and interstitial oedema and congestion in testicular tissue. LP and EA treatments to AR-treated rats markedly decreased abnormal sperm rates, testicular thiobarbituric acid reactive substances level, and increased the glutathione (GSH) level, GSH-peroxidase, catalase activities and epidiymal sperm concentration as compared with the alone AR group. Additionally, the AR-induced histopathological damages were totally or partially recovered by LP or EA administrations respectively. AR damages the testicular tissue and spermatozoa by impairing the oxidant/antioxidant balance and by increasing the apoptotic spermatogenic cell rates. However, both LP and EA have modulator effects on AR-induced reproductive dysfunction in male rats.
Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors due to their ability to act as estrogens, antiestrogens and goitrogens. The aim of this study is to ascertain whether acute postnatal treatment with 3,3',4,4'-tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult rats. Male Sprague-Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at day 21 and sacrificed at day 112. At day 112, right and left testis weights were significantly increased, whereas sperm count, motility, total motile sperm count, curvilinear velocity, average path velocity, straight-line velocity, and beat-cross frequency for motile sperm were significantly decreased in rats treated with 20 mg/kg CB 77. Sperm-oocyte penetration rate was significantly reduced in rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group. However, no changes were seen in serum testosterone, thyroid hormones, or prolactin concentrations at day 112. In summary, this study showed that postnatal exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of fertilizing oocytes in mature rats. These results suggest that the sperm functions may be more susceptible or adapt less readily than the thyroid functions to endocrine disruption caused by dioxin-like PCB congeners.
To determine whether occupational exposure to N,N-dimethylformamide (DMF) for men has adverse effects on sperm function.
Cross-sectional study.
A synthetic leather factory in Taiwan.
Twelve DMF-exposed workers in a synthetic leather factory and 8 socioeconomically matched control workers from another non-DMF-exposed manufacturing plant in the vicinity were recruited.
None.
Breathing-zone monitoring of DMF exposure covering the full work shift was implemented on each participant. Urine specimens were collected from each worker immediately after their work shift in parallel with environmental sampling. Environmental DMF and urinary N-methylformamide (NMF) levels were measured by gas chromatograph. Analysis of semen samples was performed to measure semen volume, sperm concentration, morphology, and motility in accordance with World Health Organization criteria.
Both conventional microscopy and computer-assisted semen analysis showed that sperm motility in DMF-exposed group was significantly reduced from that in controls. Motility parameters were related to urinary NMF in a dose-response manner but were not related to airborne DMF.
Workers occupationally exposed to DMF could be at risk of sperm motility perturbation. The responsible toxicant for the alterations of sperm function could be the active NMF metabolite instead of DMF, but this conclusion warrants a further complete investigation.
This study examined the effects of acute exposure to PCB99 (2,2',4,4',5-pentachlorobiphenyl), and PCB153 (2,2',4,4'5,5'-hexachlorobiphenyl), on spermatogenesis in 8-week-old C57BL6 mice. The mice were randomly allocated to PCB99 and PCB153 and a single dose of respectively 10 and 100 mg/kg was given by oral gavage. During the 6-week experiment, six mice per treatment group were sacrificed weekly, body weights were recorded and samples with respect to the male reproductive system were collected until further analysis. None of the treatments, showed changes in body weight or reproductive endpoints. Flow cytometric analysis revealed spermatogenesis to be unaffected. However, PCB99 and PCB153 showed a significant increase in Leydig cell apoptosis. The results from the present study indicate that the male reproductive system is relatively refractory to PCB99 and PCB153 at levels exceeding those of wildlife and humans, when exposed during adult life. However, the finding of apoptotic Leydig cells merits further investigation.
Persistent organochlorine pollutants (POPs) have been suggested to have negative effects on a number of hormonal systems. Several studies performed retrospectively have reported a possible association between POP exposure and fertility, measured as time to pregnancy (TTP). However, these studies lack biomarkers of exposure at the time when the women tried to conceive. It has previously been found that past female serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) can be estimated using a complex decay model, assuming that the biological half-life is 5 years, the yearly environmental reduction of the compound has been 3% since 1976, and the reduction of body burden due to lactation is 20% for periods up to 6 months and 30% for periods exceeding 6 months. In the present study, it is established that the model is valid also for estimations of past male serum concentrations of CB-153. Furthermore, the complex decay model was found to be useful also for estimating past serum concentrations of 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), assuming that the biological half-life of the compound is 8 years, the yearly reduction between 1971 and 1981 was 20% and after that 9%, and the reduction of body burden due to lactation is the same as that for CB-153. However, even though the estimated past serum concentrations of CB-153 and p,p'-DDE were found to be better proxy measures of actual past concentrations than current serum concentrations, there was little change in the rank order of the population investigated. Thus, the effect estimate for TTP was similar for both proxy measures when using categorized measures of exposure.
To determine the distribution of persistent organochlorine compounds in beef cattle, concentrations of 2,3,7,8-substituted PCDDs, PCDFs and dioxin-like PCBs were measured in the blood, testes and adipose tissue of four two-month-old Japanese Black calves. Of 29 congeners analyzed, 19, 20 and 28 were detected in the blood, testes and adipose tissue, respectively, of three or all calves. Total toxic equivalents (TEQs) were similar in the testes and adipose tissue, and approximately two times higher than in the blood on a lipid weight basis (P<0.05). More PCDDs and PCDFs had accumulated in the testes than in adipose tissue (P<0.01), but more dioxin-like PCBs were found in adipose tissue than in the testes (P<0.0001). Accumulation patterns in the testes and adipose tissue varied among the congeners of PCDD and PCDF, whereas the patterns were similar in dioxin-like PCBs. In particular, highly substituted PCDD congeners were detected at high concentrations in the testes but at lower concentrations in adipose tissue compared with other congeners. By contrast, accumulation levels of highly substituted PCDFs were lower in both those tissues than the other congeners. In conclusion, it was demonstrated that PCDDs, PCDFs and dioxin-like PCBs leave the circulation and accumulate in the testes and adipose tissue in bovine calves. It was suggested that congeners of PCDD, especially highly substituted PCDDs, and PCDFs have a tendency to accumulate in the testis and dioxin-like PCB congeners accumulate readily in adipose tissue.
Semen quality in humans may be influenced by exposure to endocrine-disrupting compounds.
We analyzed associations between semen characteristics and serum xenoestrogen receptor (XER), xenoandrogen receptor (XAR), and aryl hydrocarbon receptor (AhR) transactivity. XER and XAR activity were measured in serum samples cleared for endogenous steroid hormones and AhR activity in raw lipophilic serum extracts free of proteins.
All together, 319 men from Warsaw (Poland), Greenland, Kharkiv (Ukraine), and Sweden provided semen and blood samples. No strong and consistent associations between xenobiotic activity and semen quality measures were observed in the four populations. However, when the data were combined across populations sperm concentration increased 40% per unit increase in XER activity [95% confidence interval (CI), 1-79%] in the subgroup with XER activity below the reference level. Among subjects with XER activity above the reference level an increase of 14% (95% CI, 2-28%) was found. Furthermore, an increase of 10% motile sperm per unit increase in XER activity below reference level (95% CI, 0.2-20) was found. We are unable to exclude that the associations are chance findings.
Alteration of XER, XAR, or AhR transactivity within the range found in serum from the general European and Inuit population seems not to markedly deteriorate sperm cell concentration, motility, or morphology in adult men.
Three HRGC systems (1: 30m DB-XLB capillary with MS-SIM detection; 2: 60m DB-XLB capillary with full-scan, ion-trap MS detection; and 3: Parallel dual-column DB-17 and series-coupled HP5/HT5 with ECD detection) were used to completely characterize multiple lots of 8 different-numbered Aroclor mixtures by quantitative calibration against 9 solutions containing primary standards of all 209 PCB congeners. Despite lower absolute sensitivity and more Aroclor congener coelutions than the dual-column ECD system, the MS systems enabled measurement of more congeners per Aroclor since their greater linear response range did not require dilution of samples and standards. Pairs of different lots of Aroclors 1248 and 1254 displayed markedly different proportions of congeners, and the 1254 pair displayed strong differences in the extent of ortho-chlorine substitution. The tables of congener weight percent distributions among Aroclors are more comprehensive and quantitatively precise than those of prior publications. However, the limitations of single-level calibration precluded measurement of all congeners to the ±10% accuracy desirable for establishing these Aroclors as secondary standards for comprehensive, quantitative congener-specific PCB analysis.
Chlortetracycline (CTC) fluorescence patterns were assessed in epididymal mouse sperm suspensions capacitated in exogenous substrate-containing and substrate-free media. A capacitation-dependent transition from a majority of acrosome-intact cells expressing the uncapacitated F pattern of fluorescence to a majority with the capacitated acrosome-intact B and acrosome-reacted AR patterns was confirmed for suspensions incubated a total of 120 min in the presence of a glycolysable substrate, glucose. In contrast, assessment of spermatozoa incubated for 120 min in substrate-free medium revealed a majority of cells with the uncapacitated F pattern, despite an earlier demonstration that such cells are essentially capacitated: upon the introduction of glucose, suspensions are immediately highly fertile. When a suitable glycolysable substrate, either glucose or mannose but not fructose, was added to such suspensions, the distribution of CTC patterns changed within 10 min to a majority of B and AR patterns. Furthermore, the degree of change from uncapacitated to capacitated patterns was substrate concentration-dependent. In contrast, the introduction of the non-metabolizable substrates 2-deoxyglucose and 3-0-methylglucose and the oxidizable substrates sodium pyruvate and sodium lactate caused no change in the patterns from those seen in substrate-free medium. The in-vitro fertilizing ability of sperm suspensions to which increasing amounts of glucose or mannose were added, after initial substrate-free preincubation, directly paralleled the changes in CTC patterns and was as rapid as for suspensions incubated continuously in either hexose. We therefore conclude that the alteration in position of surface components to which CTC binds is not only capacitation-dependent, but also energy-dependent. In the absence of an appropriate exogenous glycolysable substrate, the final transition cannot occur, even though the cells are essentially capacitated.
Current evaluation of male fertility, routinely estimated by sperm count, motility, and morphology, provides only crude information about the fertility state of individuals. Both flow and image cytometry were applied to mitochondrial activity and sperm motility respectively. Sperm samples from fertile donors were concomitantly measured for Rhodamine 123 (Rh123) uptake (an estimation of mitochondrial activity), percentage of dead cells, and motility characteristics, such as percentage of motility, curvilinear velocity, and amplitude of lateral head displacement. These measurements were done under experimental conditions known to modulate sperm motility (temperature and time course survival in a capacitating medium). Bimodal distributions were found for Rh123 uptake. Flow cytometry-derived parameters were essentially time-dependent whereas motility characteristics were primarily temperature-dependent. Correlations were found between various flow cytometry-derived parameters and motility characteristics. Most of the correlations were obtained after a 24 h incubation in a capacitating medium. The most significant correlation in every experimental condition concerned the percentage of motile spermatozoa and the Rh123 uptakes. The drop in motility observed after a 24 h incubation was paralleled by a markedly lower drop in mitochondrial activity. The data suggest that these two complementary techniques represent an improvement in basic and/or clinical assessment of the functional spermatozoa status.
A multicomponent method used for analysis of organochlorine pesticides, polychlorinated biphenyls (PCBs), naphthalenes, dibenzo-p-dioxins, and dibenzofurans was adapted for the analysis of methylsulfonyl metabolites of chlorinated biphenyls (MeSO2-CBs) and of p,p'-DDE (MeSO2-DDE) in human milk. The extraction and initial purification was made by liquid-gel partitioning. Additional purification and separation steps were achieved by adsorption and gel permeation chromatography. The mean recoveries of 23 MeSO2-CBs and MeSO2-DDE standards, added to the milk before extraction, were 80-97%. Human milk sampled in Stockholm during 1972, 1976, 1980, 1984/85, 1990, 1991, and 1992 was analyzed by GC-MS. During the time course studied, the concentrations of MeSO2-CBs decreased from approximately 9 to 2 ng/g lipids and of MeSO2-DDE from 5 to 0.4 ng/g lipids. The concentrations of MeSO2-CBs and MeSO2-DDE correlated to the levels of total PCB and p,p'-DDE, respectively. 3-MeSO2-DDE was the major isomer of the aryl methyl sulfones studied in the milk. PCB methyl sulfones with five and six chlorine atoms in the molecule were predominant among the PCB methyl sulfones Generally, the concentrations of 4-MeSO2-CBs were higher than the corresponding 3-MeSO2-CB compound. The major MeSO2-CBs in the milk were 4-MeSO2-2,5,2',3',4'-pentaCB (4-87) and 4-MeSO2-2,3,6,2',4',5'-hexaCB (4-149).
Polychlorinated biphenyls (PCBs) with the liable 2,3,6-substitution are important components of certain commercial mixtures and frequently detected in biota, but little is known about their enzyme induction abilities and possible endocrine-disrupting effects. CB 132 (2,2',3,3',4,6'-hexachlorophenyl) and CB 149 (2,2'3,4',5',6-hexachlorophenyl) were investigated in weanling female rats dosed intraperitoneally on days 21 and 22 and killed on day 24 of age. Uterotropic response, serum thyroid hormone, and hepatic enzyme induction were examined in prepubertal female rats treated with these two environmentally relevant 2,3,6-substituted chlorobiphenyl (CB) congeners from 8 mg/kg to 96 mg/kg. The readily metabolized CB 132 did not cause any significant increase in all endpoints measured in the present study. On the other hand, CB 149 was a weak PROD and BROD inducer and a modest depleter of serum thyroxine in prepubertal female rats. The finding of thyroid hormone disruption by CB 149 may lead to biologically significant neurobehavioral and neurochemical changes in developing animals via milk lactation.
Polychlorinated aromatic hydrocarbons (PCAHs) have been described as endocrine disruptors in animals and in accidentally or occupationally exposed humans. In the present study we examined the effect of moderate exposure to PCAHs on sexual maturation. Two hundred adolescents (mean age, 17.4 years) who resided in two polluted suburbs and a rural control area in Flanders (Belgium) participated. We measured the serum concentration of polychlorinated biphenyl (PCB) congeners 138, 153, and 180 and dioxin-like compounds [chemically activated luciferase expression (CALUX) assay] as biomarkers of exposure. School physicians assessed the pubertal development of boys and girls and measured testicular volume. In one suburb near two waste incinerators, compared with the other suburb and the control area, fewer boys (p < 0.001) had reached the adult stages of genital development (62% vs. 92% and 100%, respectively) and pubic hair growth (48% vs. 77% and 100%). Also, in the same suburb, fewer girls (p = 0.04) had reached the adult stage of breast development (67% vs. 90% and 79%). In individual boys, a doubling of the serum concentration of PCB congener 138 increased the odds of not having matured into the adult stage of genital development by 3.5 (p = 0.04); similarly for PCB congener 153 in relation to male pubic hair growth, the odds ratio was 3.5 (p = 0.04). In girls, a doubling of the serum dioxin concentration increased the odds of not having reached the adult stage of breast development by 2.3 (p = 0.02). Left plus right testicular volume was lower in both polluted areas than in the control area (42.4 mL vs. 47.3 mL, p = 0.005) but was not related to the current exposure of the adolescents to PCAHs. Through endocrine disruption, environmental exposure to PCAHs may interfere with sexual maturation and in the long-run adversely affect human reproduction.
Enantioselective analysis of the chiral polychlorinated biphenyls (PCBs) 95, 132 and 149 in river sediment samples was carried out by multidimensional gas chromatography with an achiral-chiral column combination and electron-capture detection. The investigations revealed the PCB congeners analysed to be present racemic within experimental error. A micro simultaneous steam distillation-solvent extraction device was used as extraction method. This technique proved to be a versatile tool for the extraction of organochlorine compounds from several matrices and was used for the extraction of PCBs from sediment samples. The removal of interfering elementary sulfur was carried out by the treatment with copper powder during the extraction.
Blubber and liver samples from six striped dolphins (Stenella coeruleoalba) found dead in the Mediterranean sea in 1989−1990 were tested for 37 coplanar and chiral polychlorinated biphenyls (PCBs), including the enantiomeric ratios of 9 chiral PCBs. The method includes a fractionation step using HPLC (PYE column) for separating the PCBs according to the number of chlorine atoms in the ortho positions. HRGC/ECD and HRGC/LRMS with an achiral column (DB-5) were used to determine the PCB congeners. The enantiomeric ratios of nine chiral PCBs were determined by HRGC/LRMS (SIM) with a chiral column (Chirasil-Dex) and by MDGC as the confirmatory technique. The total PCB concentration (sum of 37 congeners) ranged from 7.2 to 89.6 μg/g (wet weight) and from 0.52 to 29.2 μg/g (wet weight) for blubber and liver samples, respectively. PCB profiles were dominated by congeners 138, 153, 170, and 180. The toxic equivalent values (TEQ) ranged from 0.17 to 3.93 ng/g (wet weight) and from 0.02 to 0.73 ng/g (wet weight) for blubber and liver samples, respectively. PCBs 95, 132, 135, 149, and 176 revealed an enantiomeric excess of the second eluted enantiomer in almost all of the samples, whereas PCBs 136 and 174 were racemic or almost racemic. PCBs 88 and 91 were under the detection limits of the methodology used.
Isomer-specific concentrations of 41 polychlorinated biphenyls (PCBs) and the enantiomeric ratios (ER) of nine chiral PCBs were determined in the liver of four cetacean species—Risso's dolphin (Grampus griseus), bottlenose dolphin (Tursiops truncatus), fin whale (Balaenoptera physalus), and long-finned pilot whale (Globicephala melaena)—found dead in the Mediterranean Sea. The total PCB concentration (sum of 41 congeners) ranged from 484 to 63,200 ng/g wet weight. The 2,3,7,8 tetra-chlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQs), as defined by the World Health Organization (WHO), ranged from 4.3 to 1,454 pg/g wet weight. The contribution of mono-ortho PCBs was consistently higher than non-ortho PCB congeners, in whale species, whereas in dolphins this predominance was not so clear. The PCB profiles were dominated by congeners 138, 153, and 180 in almost all the investigated samples. Comparison of PCB profiles by using principal component analysis allowed to separate the species into different groups. Polychlorinated biphenyls 170 and 180 seem to be eliminated by the two whale species, and PCB 180 also seems to be eliminated by Risso's dolphins. The PCBs 95, 132, 149, and 176 revealed an enantiomeric excess of the second eluted enantiomer in almost all the cetaceans investigated, where 136 and 174 were racemic or almost racemic. It is the first time that an enantiomeric excess of PCB 84 and 91 has been reported in biological samples. Although it was only possible to calculate them in two dolphin liver samples, the high values of enantiomeric excess found are surprising (86.3 and 32% for PCB 91 and 84, respectively).
Our previous studies have found that early exposure to polychlorinated biphenyls (PCBs) through milk of the dam can affect fertility when male offspring reach adulthood. A significant proportion of ovulated eggs in normal females mated to PCB-exposed males do not implant. This effect does not appear to be related to reduced weight gain of pups during PCB exposure. In this study, dams with litters were given peanut oil or a PCB mixture (Aroclor 1254) in oil at doses of 8, 16, 32 and 64 μg/g (PCBI, II, III, IV) on days 1,3,5,7 and 9 of lactation. At 120 d of age the male offspring were mated to normal females. Oviducts/uteri of sperm-positive females were flushed and eggs examined at the expected pronuclear, two- to four-cell and blastocyst stages of development. We observed either a significant decrease or a decline in number and percent of normal fertilized eggs and eggs at the two- to four-cell and blastocyst stages in females mated to male offspring of PCBII, III and IV. Neither reduced ventral prostate weights nor an increased incidence of a right kidney abnormality were correlated with reduced fertility. Caudal sperm reserves, sperm production, epididymal sperm morphology and FSH levels were not affected; testosterone levels were not reduced as compared to those of controls. With one exception, epididymal sperm motility parameters were not significantly different. It appears that early postnatal exposure to PCBs affects ability of sperm to fertilize eggs but not production, morphology or motility of epididymal sperm.
The enantiomeric ratios of the chiral polychlorinated biphenyls 2, 2′, 3, 5′, 6-pentachlorobiphenyl (PCB 95) and 2, 2′, 3,
4′, 5′, 6-hexachlorobiphenyl (PCB 149) were determined in human milk samples by multidimensional gas chromatography, using
two different achiral columns for preseparation and a chiral column for enantiomeric separation. Detection was carried out
by electron capture detection and by mass spectrometry in the single ion monitoring mode. For PCB 95 a slight enrichment of
the first eluted peak was determined whereas PCB 149 is present as racemate.
Alterations in the liver of male and female Sprague-Dawley rats fed PCB congener 153 (2,2′,4,4′,5,5′-hexachlorobiphenyl) at 0.5, 5, or 50 ppm concentrations in diets for 13 weeks were determined morphometrically. A dose-dependent increase in hepatocyte volume was detected; the cytoplasmic compartment contributed to the increase in cell volume in an overwhelming fashion. Eighty percent and 250% increase in smooth endoplasmic reticulum volume and its surface area in hepatocytes were estimated in animals of both genders from 5- and 50-ppm groups, respectively; the organelle played the largest part in the increase in cytoplasmic volume. Rough endoplasmic reticulum alteration was shown to depend on gender, where the volume per hepatocyte was augmented by 40% and 45% in females of 5- and 50-ppm groups, respectively, however, 30% and 20% decreases in volume of this organelle were noted in males at those congener concentrations. A decrease of 13% in normal mitochondria volume at 50 ppm concentration was observed, which may have been a consequence of a transformation of these mitochondria to abnormal types. Two types of abnormal mitochondria, named Type I and Type II, were defined: the former comprised mitochondria that had cristae which laying parallel to the long axis of the organelle and the latter showed C- or ring-shaped profiles. Data analysis revealed a trend toward an increase in abnormal mitochondria volume in the cells as the congener concentration elevated. In addition, a threefold increase in the volume of lysosomal elements per hepatocyte was noted in 50 ppm PCB-fed rats of both genders. Also, a significant increase in peroxisome volume per cell in female rats was detected at a lower concentration than it was in the male. This study, which is a first ultrastructural quantitative investigation on the effects of a PCB that included many parameters. The methodology, and the data may prove useful to provide better understanding of pathology in the evaluation and regulation of toxic chemicals.
As little information is available on the adverse effects of polychlorinated biphenyls (PCBs) on the reproductive system of the male rat, the current study was conducted to evaluate the effects of subchronic administration of the PCB mixture Aroclor 1254 on testicular gamete production and endocrine function. The thyroid hormone thyroxine (T4), which is critical for reproduction and development, was also measured because of the well-documented effects of PCBs on this hormone. Weanling (31-day-old) male Fischer rats, were administered 0, 0.1, 1, 10, or 25 mg/kg/day Aroclor 1254 by gavage for 5, 10, or 15 weeks and necropsied. The hormones testosterone (T) and thyroxine were measured in the serum, and body weight and weights of the liver, kidney, testes, seminal vesicle plus coagulating gland, cauda epididymides, and pituitary were taken. At 10 and 15 weeks, testicular interstitial fluid (IF) was collected and T concentration in the IF was measured. Sperm motility was measured from a caudal sperm sample and sperm numbers in the testis and cauda epididymis were determined. In addition, tissues were examined microscopically for histopathological alterations. In the high-dose group, body, seminal vesicle, cauda epididymal, and pituitary weights were depressed at 10 and 15 weeks and cauda epididymal sperm numbers were reduced after 15 weeks of dosing. In contrast, testes weights, testicular sperm numbers, sperm motility, and serum and testicular testosterone levels were unaffected, even in the highest dose group (25 mg/kg/day). Aroclor 1254 administration produced histological alterations in the liver and kidney at doses of 1.0 mg/kg/day and above. These results indicate that the testis of the rat is not a specific target organ for Aroclor 1254. In contrast, serum T4 lelvels were reduced by Aroclor 1254 administration at a dose 250-fold below the dose that failed to alter testicular function. Serum T4 levels were depressed 25% in the 1 mg/kg dose group after 5 weeks of exposure and 30% in the 0.1 mg/kg group following 15 weeks of exposure. T4 levels were undetectable in the two highest (10 and 25) dose groups at all intervals. The fact that the decreases in T4 were generally concurrent with increases in liver weight suggested that Aroclor 1254 altered T4 levels by increasing the turnover rate in the serum by enhancing the metabolism of T4 by the liver. The reduction in serum T4 reported here occurred at a dose 25-fold lower than the dose generally recognized as affecting thyroid hormone levels.
Polychlorinated biphenyls (PCBs) are ubiquitous global contaminants that have been intensively investigated for three decades. They are broad-acting toxicants occurring in complex mixtures and accurate risk assessment has proven to be elusive. Focusing on a limited set of end points and emphasizing a fixed set of congeners have led to more streamlined data sets that are meant to expedite hazard characterization and risk assessment for the most potent congeners--aryl hydrocarbon receptor (AhR) agonists. Unfortunately, this has made it impossible to confirm or deny significant contributions from the more prevalent components of the mixtures. PCBs may be only coincidentally present, rather than causal, in some diseases. Still, attempts to determine associations with incomplete residue data may lead to erroneous conclusions and make accurate risk assessment even more elusive. Responses not mediated through the AhR are presented and emphasize large data gaps. Dissimilar analytical reports emphasize that selection of analytes is not consistent. Collectively, these data confirm that AhR-focused objectives unintentionally created the impression that nonplanar PCBs have little if any potential for hazards to humans and wildlife. Near steady-state exposure of healthy adults are probably of minor consequence except for emerging correlations with non-Hodgkin's lymphoma; however, pulses of exposure to more labile mixtures may contribute to developmental effects without leaving a residue record. More broadly based criteria are suggested and harmonization of data collection and presentation are desirable. A more comprehensive list of PCB congeners is proposed that would provide more adequate data upon which to base associations with adverse outcomes.
A 30% solution of a polychlorinated biphenyl (PCB) mixture or a microscope immersion oil containing 34% PCB, when applied to the skin of rats, led to substantial increases in the biliary excretion of intravenously injected [125I]thyroxine (T4) in bile: plasma 125I ratios, in the biliary clearance rate of plasma [125I]T4, and in bile flow. Both PCB preparations also elevated liver weight, thyroid 125I uptake, and Sephadex uptake of [125I]triiodothyronine (T3), and depressed serum T4 concentrations; serum T3 levels were unaltered by the PCB solution or by the immersion oil containing PCB. PCB, either in mineral or immersion oil, reduced the free T4 index (serum T4 X fraction Sephadex T3 uptake), indicating a probable reduction in the concentration of free T4 in serum; the free T3 index, on the other hand, was elevated in PCB-treated rats. The same type of immersion oil, in which the PCB was replaced by a hydrogenated terphenyl, was without effect on any of the indices studied. Thus, the effects of microscope immersion oil on T4 metabolism were due to its PCB content. In thyroidectomized, T4-maintained rats, PCB in mineral oil again increased Sephadex uptake of [125I]T3, greatly reduced serum T4, and moderately reduced serum T3 levels; the free T4 index was substantially reduced and the free T3 index moderately lowered in treated animals. These data indicate that in PCB-treated rats both the peripheral conversion of T4 to T3 and thyroid T3 secretion were enhanced. The metabolic impact of thyroid hormone in PCB-treated animals was unchanged, as shown by normal activity of hepatic mitochondrial L-alpha-glycerophosphate dehydrogenase.
When administered in overtly toxic doses to postpubescent rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces a variety of adverse effects on the male reproductive system including a decrease in plasma androgen concentrations. If such an androgenic deficiency were produced prenatally and/or early postnatally it could potentially impair male reproductive function by disrupting the development of sex organs and/or causing incomplete sexual differentiation of the central nervous system. To determine whether TCDD can reduce androgen concentrations perinatally and/or impair androgen-dependent perinatal development, pregnant Holtzman rats were treated with 1.0 micrograms TCDD/kg or vehicle on Day 15 of gestation. Plasma testosterone concentrations in fetal males were significantly reduced by TCDD on Gestation Days 18 through 21. The surge in plasma testosterone concentrations shortly after birth was also significantly reduced, as was anogenital distance, an androgen-dependent parameter. To further investigate the effects of perinatal TCDD exposure on the male reproductive system, rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated from birth through sexual maturation. This report describes their growth, physical development, and androgenic status (i.e., androgen concentrations and androgen-dependent structures and functions); effects on spermatogenesis, testicular histology, sexual behavior, and fertility are reported separately. There was little evidence that TCDD caused maternal toxicity. Signs of overt toxicity in offspring were limited to an 8% reduction in live births (highest dose only) and to decreases in body weight gain and feed consumption (two highest doses only) which disappeared by early adulthood. With respect to androgenic status, maternal TCDD doses as low as 0.16 micrograms/kg produced significant dose-related decreases in the anogenital distance of 1- and 4-day-old males, delays in testicular descent, and decreases in seminal vesicle and ventral prostate weights. The reductions in organ weights were observed when rats were at the juvenile, pubertal, postpubertal, and mature stages of sexual development. Plasma testosterone and 5 alpha-dihydrotestosterone concentrations tended to be reduced at these times (though not significantly), while plasma luteinizing hormone concentrations were generally unaffected. Collectively, these results demonstrate that perinatal TCDD exposure alters the androgenic status of male rats from the fetal stage into adulthood, and that TCDD can affect androgenic status without causing overt toxicity. In rats, the male reproductive system appears to be more sensitive to the toxic effects of in utero and lactational TCDD exposure than any other organ or organ system studied thus far.
When administered in overtly toxic doses to postweanling male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces adverse effects on the reproductive system including a decrease in spermatogenesis. Because the male reproductive system may be particularly susceptible to toxic insult during the perinatal period, the effects of in utero and lactational TCDD exposure on its development were examined. Male rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated at various stages of development; effects on spermatogenesis and male reproductive capability are reported herein. Testis, epididymis, and cauda epididymis weights were decreased in a dose-related fashion at 32, 49, 63, and 120 days of age, that is, when males were at the juvenile, pubertal, postpubertal, and mature stages of sexual development, respectively. When measured on Days 49, 63, and 120, daily sperm production by the testis was reduced at the highest maternal TCDD dose to 57-74% of the control rate. Cauda epididymal sperm reserves in 63- and 120-day-old males were decreased to as low as 25 and 44%, respectively, of control values, although the motility and morphology of these sperm appeared to be unaffected. The magnitude of the effects described above tended to lessen with time; nevertheless, the decreases in epididymis and cauda epididymis weights, daily sperm production, and cauda epididymal sperm number were statistically significant at the lowest maternal dose tested (0.064 micrograms TCDD/kg) on Day 120 and at most earlier times. To determine if in utero and lactational TCDD exposure also affects male reproductive capability, rats were mated at approximately 70 and 120 days of age with control females. Little if any effect on fertility was seen, and the survival and growth of offspring was unaffected. These results are not inconsistent with the pronounced reductions in daily sperm production and cauda epididymal sperm reserves caused by perinatal TCDD exposure since rats produce and ejaculate far more sperm than are required for normal fertility. The TCDD-induced reduction in spermatogenesis cannot be accounted for by concurrent effects on plasma follicle-stimulating hormone or androgen concentrations or by undernutrition. To investigate the nature of the spermatogenic lesion, leptotene spermatocyte to Sertoli cell ratios were determined.(ABSTRACT TRUNCATED AT 400 WORDS)
Molecular/theoretical modeling studies have revealed that thyroid hormones and toxic chlorinated aromatic hydrocarbons of environmental significance (for which dioxin or TCDD is the prototype) have similar structural properties that could be important in molecular recognition in biochemical systems. These molecular properties include a somewhat rigid, sterically accessible and polarizable aromatic ring and size-limited, hydrophobic lateral substituents, usually contained in opposite adjoining rings of a diphenyl compound. These molecular properties define the primary binding groups thought to be important in molecular recognition of both types of structures in biochemical systems. Similar molecular reactivities are supported by the demonstration of effective specific binding of thyroid hormones and chlorinated aromatic hydrocarbons with four different proteins, enzymes, or receptor preparations that are known or suspected to be involved in the expression of thyroid hormone activity. These binding interactions represent both aromatic-aromatic (stacking) and molecular cleft-type recognition processes. A multiple protein or multifunctional receptor-ligand binding mechanism model is proposed as a way of visualizing the details and possible role of both the stacking and cleft type molecular recognition factors in the expression of biological activity. The model suggests a means by which hormone-responsive effector-linked sites (possible protein-protein-DNA complexes) can maintain highly structurally specific control of hormone action. Finally, the model also provides a theoretical basis for the design and conduct of further biological experimentation on the molecular mechanism(s) of action of toxic chlorinated aromatic hydrocarbons and thyroid hormones.
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Studies were directed at the question of whether polychlorinated biphenyl (PCB; Aroclor 1254) and polybrominated biphenyl (PBB; Fire Master BP-6), when administered in the diets of female Sprague-Dawley rats over long periods of time (5-7 months) and at low dosages (0, 1, 5, 10, and 50 ppm), would depress the thyroid. By examining serum T3 and T4, kinetics of T4 metabolism, and in vivo thyroid response to exogenous TSH injections, an estimate of the degree of hypothyroidism was made, and abnormalities in T4 disappearance from serum were encountered. Serum T3 and T4 levels were greatly suppressed in a dose-related manner by PCB or PBB treatment. There was a diminished response of serum T3 and T4 to TSH injection in rats pretreated with PCB or PBB (5 and 10 ppm), the exception being T3 in the 5 ppm PCB treatment group. Had the PCB and PBB treatment-induced suppression of T4 and T3 been on the hypothalamo-pituitary axis, the response of the treated rats to exogenous TSH might have exceeded that of controls; however, the opposite occurred. Disappearance of injected doses of L-[125I]T4 diminished as treatment concentrations of PCB or PBB increased. Disappearance slopes (r = 0.98) and fractional turnover rate constants (k) were decreased (t1/2 was lengthened) at each treatment level compared to the control values. The T4 distribution space (per 100 g BW) was expanded with increasing dosage by as much as 8-fold in the 50 pmm PCB treatment group. T4 MCRs were not increased by PCB or PBB treatment; thus, decreases in serum T3 and T4 were not caused by increased catabolism. T4 production rates were decreased at all treatment levels, but maximally 6-fold by 50 ppm PCB treatment. Together these data indicate that PCB-PBB-induced decreases in serum T3 and T4 result primarily from direct damage to the thyroid rather than any enhanced hepatic or other peripheral catabolism per se. Expanded T4 distribution space demonstrated that nonthyroid damage was also an important factor in reducing serum T4. Cell membrane damage associated with PCB-PBB intoxication may have expanded pools for T4 dilution. The findings are consistent with reported histological and ultrastructural damage caused by PCB and PBB. It also appears that TSH plays little role in PCB-PBB-induced hypothyroidism.
Polychlorinated biphenyls (PCBs) have been found widely distributed in the ecosystem, including human milk, yet there is limited information concerning the effect that PCB exposure during the postnatal period might have on subsequent reproductive capacity of adult male offspring. In this study, fertility and condition of reproductive organs were examined in male offspring of rats that received Aroclor 1254 orally (8, 32, or 64 mg/kg) on Days 1-3, 5, 7, and 9 of lactation. It was found that the experimental male offspring as adults were less successful in mating and reproducing when compared with control offspring. Virgin females mated with males exposed through suckling to the two higher doses of PCBs had a significantly lower proportion of ovulated eggs that implanted, a significantly lower number of live fetuses, and a significantly higher rate of resorption. At autopsy, although body weights were not significantly different, ventral prostate weights were significantly less in all treated male offspring; there were fewer alveoli and flattened epithelial cells in these glands as compared to controls. Seminal vesicle weights were significantly less in males exposed to the two higher doses of PCBs, while the testes were significantly larger. PCB-derived material remained in adipose tissue and liver at the time of autopsy. These data support the hypothesis that exposure of male offspring to PCBs during early postnatal development results in an hypoandrogenic condition that is detrimental to normal reproductive functioning in the adult.
This paper reviews the Food and Drug Administration (FDA) analysis of the risk to humans from consuming fish contaminated with polychlorinated biphenyls (PCBs). In brief, the FDA methodology employed "high" dose experiments on animals and extrapolated the observed rates of certain types of cancer at these elevated doses to the low doses found in human diets. These extrapolations were then used to define a recommended tolerance level of 5 ppm, and proposed reduction to 2 ppm, for fish sold in interstate commerce. Unfortunately, as is shown here, such a procedure is extremely sensitive to the basis for extrapolation. Important elements of the FDA analysis include the following: (i) FDA assumed a particular form of the dose-response model: the one-hit model. Many other models have been proposed and, on balance, appear equally plausible. These models estimate lower risks than does the one-hit model. (ii) FDA calculated 99% upper confidence bounds on these risks and, moreover, emphasized cases of fish eaters who consume greater amounts of PCB-contaminated fish than do 98.5% of the U.S. population. (iii) FDA based PCB ingestion computations on consumption of raw fish, whereas most fish are cooked before eating, and it is known that PCB levels in cooked fish are lower than PCB levels in raw fish. (iv) FDA based estimates of cancer risk on the assumption that PCB levels in fish would be constant over the nominal 70-year human life span used in the FDA "lifetime risk" computation. Recent data suggest that PCB levels have been declining in fish (particularly in sport fish) and humans as well. Such trends imply significantly lower cumulative lifetime PCB doses than were assumed in the FDA analysis. (v) FDA assumed that humans and test animals are equally sensitive to PCB ingestion when measured on a parts per million in diet basis. Extrapolations on an equivalent consumption per unit of body weight, thought appropriate by most researchers, result in much lower health risks. In short, when confronted with methodological choices, the FDA consistently selected "worst case" or conservative assumptions over other alternatives of at least equal plausibility. This philosophy of choice was explicitly acknowledged by the FDA. What was omitted from the FDA analysis, however, was the possible degree of overstatement of these risks. The results of replicate risk computations using alternative assumptions to examine the possible magnitude of overstatement of health risk are summarized in Table 12. As can be seen, this overstatement could easily account for a discrepancy of several orders of magnitude between actual and calculated risks.(ABSTRACT TRUNCATED AT 400 WORDS)
The enantiomeric ratio (ER) of the chiral polychlorinated biphenyl (PCB) 132 (2,2',3,3',4,6'-hexachlorobiphenyl) was determined in human milk samples. The enantiomers were separated by multidimensional gas chromatography (MDGC), using different achiral columns for pre-separation and a Chirasil-Dex column for enantiomer separation, and quantified by electron-capture detection (ECD) and by mass spectrometry (MS/SIM). The determined enantiomeric ratios varied between 0.45-0.85 (enantiomeric excess: 38-8%).
As little information is available on the adverse effects of polychlorinated biphenyls (PCBs) on the reproductive system of the male rat, the current study was conducted to evaluate the effects of subchronic administration of the PCB mixture Aroclor 1254 on testicular gamete production and endocrine function. The thyroid hormone thyroxine (T4), which is critical for reproduction and development, was also measured because of the well-documented effects of PCBs on this hormone. Weanling (31-day-old) male Fischer rats were administered 0, 0.1, 1, 10, or 25 mg/kg/day Aroclor 1254 by gavage for 5, 10, or 15 weeks and necropsied. The hormones testosterone (T) and thyroxine were measured in the serum, and body weight and weights of the liver, kidney, testes, seminal vesicle plus coagulating gland, cauda epididymides, and pituitary were taken. At 10 and 15 weeks, testicular interstitial fluid (IF) was collected and T concentration in the IF was measured. Sperm motility was measured from a caudal sperm sample and sperm numbers in the testis and cauda epididymis were determined. In addition, tissues were examined microscopically for histopathological alterations. In the high-dose group, body, seminal vesicle, cauda epididymal, and pituitary weights were depressed at 10 and 15 weeks and cauda epididymal sperm numbers were reduced after 15 weeks of dosing. In contrast, testes weights, testicular sperm numbers, sperm motility, and serum and testicular testosterone levels were unaffected, even in the highest dose group (25 mg/kg/day). Aroclor 1254 administration produced histological alterations in the liver and kidney at doses of 1.0 mg/kg/day and above.(ABSTRACT TRUNCATED AT 250 WORDS)
Time-mated Sprague-Dawley rats were exposed to PCB 28 (2,4,4'-trichlorobiphenyl), 8 or 32 mg/kg/day; PCB 118 (2,3',4,4',5-pentachlorobiphenyl), 4 or 16 mg/kg/day; or PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl), 16 or 64 mg/kg/day. At weaning, serum thyroxine (T4) was markedly depressed in pups, but not dams, exposed to PCB 118 or 153. Triiodothyronine (T3) was unchanged in pups and dams. In a histological evaluation of thyroids, the PCB 118 pups revealed changes suggestive of sustained TSH stimulation, including increased follicular cell vacuolization and height, increased nuclear vesiculation, and decreased colloid area. Decreases in body and brain weights and increases in liver weights were observed in some groups, with the high dose PCB 118 pups showing the greatest effect.
The chlortetracycline fluorescence assay was used to study the status of capacitation and the extent of induced acrosome reactions in cauda epididymidal spermatozoa from fertile and infertile rats fed, respectively, with vehicle or ornidazole (400 mg kg-1 day-1) for 10 days. Uniform bright fluorescence over the whole head was classified as the uncapacitated pattern, whereas a postacrosomal dark band, and a uniformly weaker fluorescence over the acrosome, reflected patterns intermediate between the uncapacitated and acrosome-reacted states. Acrosome-reacted spermatozoa displayed a dark head but always retained fluorescence at their tip. There was no difference between experimental and control groups of rats with regard to the development of the chlortetracycline fluorescence patterns during incubation. Under basal incubation conditions, the acrosome reaction was slightly delayed in spermatozoa from ornidazole-treated animals. In contrast, more spermatozoa were acrosome reacted in this group after incubation for 5 h when the concentration of BSA was increased from 4 to 20 mg ml-1. The Ca(2+)-ionophore A23187 induced a similar stimulation of capacitation and acrosome reactions in spermatozoa from control and ornidazole-fed animals, but in the latter group A23187 caused strong immobilization of spermatozoa. In the capacitation medium containing 5 mmol lactate l-1 and 5 mmol glucose l-1, the straight-line velocity of spermatozoa from ornidazole-treated rats was reduced by 50% compared with controls, irrespective of the concentration of BSA. Two glycolytic enzymes, triose phosphate isomerase and glyceraldehyde 3-phosphate dehydrogenase, displayed reduced activity (48% and 68% of controls, respectively) in cauda epididymidal spermatozoa from ornidazole-fed rats, whereas the activities of hexokinase and lactate dehydrogenase remained unchanged. This finding suggests that the fertility-compromising action of ornidazole is due to a disturbed glycolytic pathway.
Subchronic exposure to the PCB congener 77 (PCB 77) and 28 (PCB 28) was previously shown to induce histological changes in the thyroid and in the brain biogenic amines levels, suggesting possible effects on thyroid and reproductive hormone levels. Thus, the effects of a 90-day dietary exposure to PCB 28 or 77 on luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations were studied in male rats, as well as the levels of thyroid-stimulating hormone, thyroxine (T4) and uridine diphosphate-glucuronyl transferase (UDP-GT) activity in both genders. Weanling Sprague Dawley rats were randomly distributed into groups of 10 rats and were fed, for the next 13 weeks, purina lab chow containing 50, 500, 5,000 or 50 000 ppb of PCB 28 or 10, 100, 1000, or 10 000 ppb of PCB 77. The serum concentrations of T4 were decreased in rats of both sexes receiving 1000 ppb or more of PCB 77, and was associated with an increased activity of UDP-GT which reached significance only in the females. There was a tendency for the highest dose of PCB 28 also to decrease serum T4 concentrations in the female rats. None of the PCB treatments significantly altered gonadotropin, TSH, or testosterone concentrations. These results suggest that thyroid functions may be more susceptible or adapt less readily than the pituitary gland and the testes to endocrine disruption caused by PCB congeners.
Methylsulfonyl metabolites of chlorinated biphenyls (MeSO2-CBs) and p,p'-DDE (MeSO2-DDEs) were determined in human adipose and liver tissues obtained at autopsy of seven Swedish individuals 47-80 years of age. Twenty MeSO2-CBs and two MeSO2-DDEs were found in the analyzed samples. In adipose tissue, most of the 4-MeSO2-CBs were found at higher concentrations than the corresponding 3-MeSO2-CBs and, in all samples of adipose tissue, 4-MeSO2-2,2',3',4',5-pentaCB (4-87) and 4-MeSO2-2,2',3,4',5',6-hexaCB (4-149) occurred at higher concentrations than other MeSO2-CBs. In the liver, 3-MeSO2-2,2',3',4',5,6-hexaCB (3-132) was by far the most abundant MeSO2-CB, contributing to 61-82% of the sum of MeSO2-CBs. In this tissue, most of the other 3-MeSO2-CBs were also found at higher concentrations than the corresponding 4-MeSO2-CBs. The ratios of the sum of MeSO2-CBs to the sum of determined chlorinated biphenyls (CBs) were 1/250 and 1/28 in adipose tissue and the liver, respectively, calculated from the median values. The concentration of 2-MeSO2-DDE was lower than that of 3-MeSO2-DDE in both adipose tissue and liver, except in the liver from one of the individuals. The concentration ratios of 2-MeSO2-DDE to 3-MeSO2-DDE were about 10 times higher in liver than in adipose tissue. The ratios of the sum of MeSO2-DDEs to p,p'-DDE were 1/455 and 1/61 in adipose tissue and liver, respectively, calculated from the median values. MeSO2-CBs and MeSO2-DDEs were also determined in lung tissue from one of the individuals. In this sample, the profiles of MeSO2-CBs and MeSO2-DDEs were similar to the profiles of these compounds in adipose tissue.
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This study investigated the effects of 3,3',4,4'-tetrachlorobiphenyl (TCB) on the reproductive performance and in vitro sperm fertilizing ability of male mice. C57BL/6J female mice (F-0) were fed diets containing 0, 3, or 30 ppm TCB for 2 weeks before pairing with nontreated males for a 10-day breeding period. Females were continued on their treatment diet throughout mating, gestation, and lactation. Male offspring (F-1) were given the same diet as their dams throughout this study. F-1 males at 7 and 17 weeks of age were mated to nontreated B6D2-F1 female mice. Body weight, litter size, and survival indices of offspring sired by F-1 males were recorded. Sperm fertilizing ability of F-1 males at 9 and 19 weeks of age was examined in vitro using eggs collected from nontreated B6D2-F1 females. Sperm motion analysis was performed at the same time. When 7- and 17-week-old F-1 males were mated to nontreated females, no differences in fecundity, litter size, sex ratio, or survival indices among any of the treatments were observed. However, sperm fertilizing ability of 30 ppm-treated F-1 males at 19 weeks of age was less than that of the control mice. Testes weights were greater in 3-week-old, 30 ppm-treated mice.
1 The aim of this study was to ascertain the reproductive effects of PCB 77 on adult male rats and to determine its concentration in the liver and testis. Adult male rats (n = 15/group) were treated subcutaneously with a single dose of 18 mg/kg bw (PC18) or with 60 mg/kg bw (PC60). The substance was dissolved in a 10 ml volume of peanut oil/kg. Control rats received the same volume of the vehicle. The reproductive effects as well as the concentration of PCB 77 in the liver and testis were investigated 1, 4 and 8 weeks after treatment. 2 In both groups, the daily sperm production (DSP; x10(6)) remained permanently reduced in the PC18 as well as in the PC60 groups throughout the entire investigation period (DSP week 8: control: 31 +/- 7; PC18: 22 +/- 5; PC60: 20 +/- 7). The sperm number (x10(6)) per cauda epididymis was affected only at the 1st and 4th week after treatment (control week 1: 211 +/- 67; PC18 week 1: 135 +/- 62; PC60 week 1: 142 +/- 49). Moreover, a significant increase in the percentage of abnormal sperm was observed 4 weeks following treatment in the PC18 and PC60 groups and 8 weeks after treatment in the PC60 group. Abnormal tails were the most frequent changes observed. 3 The relative testicular and prostata weights (g) were slightly increased in the PC60 group at the 1st and 4th week following treatment (testis weight: control/I: 0.46 +/- 0.02; PC60/I: 0.51 +/- 0.03). 4 The serum testosterone concentrations and effects on testis morphology were not reported. 5 The maximum concentration of PCB 77 was detected in the liver and testis 1 week after treatment. The concentration declined 4 weeks after treatment in both organs, but still a significant amount of PCB 77 was detectable in the liver as well as in the testis 8 weeks after treatment. 6 The results demonstrate that PCB 77 affects sperm variables when applied to adult rats and that the elimination of PCB 77 in the testis parallels that of the liver.
1. Pregnant Wistar rats were treated orally with a single dose of 100 microg 3,3',4,4'-tetrachlorobiphenyl (PCB 77)/kg b.w. or 10 microg 3,3',4,4',5 pentachlorobiphenyl (PCB 126)/kg b.w. on day 15 of pregnancy. The control rats received peanut oil at the same day. Developmental landmarks were assessed in all offspring rats and reproductive effects of PCB 77 and PCB 126 on male offspring were studied on postnatal day 65 (at puberty) and on postnatal day 140 (at adulthood). 2. The ano-genital distance as well as the ratio ano-genital distance to body length was reduced in male pups of the PCB 126 group and the age at vaginal opening was significantly delayed in the female pups. 3. Testis, brain weights and daily sperm production were permanently increased and seminal vesicle weights were decreased in male offspring of the PCB 77 group. In male rats of PCB 126 group, the brain weights were permanently increased and ventral prostate weights permanently reduced. In both PCB groups, however, serum testosterone concentration was reduced only at adulthood. Additionally, the male rats of the PCB 126 group showed alterations in sexual behavior. In these rats the number of mounts with intromissions was significantly increased. 4. The results of this study show that PCB 126 elicits some TCDD-like reproductive effects after in utero exposure, while the reproductive effects of in utero exposure to PCB 77 on male offspring may be attributed to the neonatal hypothyroidism induced by the substance during early fetal development. Further studies using multiple doses and providing thyroid hormone data will be necessary to support this hypothesis.
As part of a multidisciplinary toxicological investigation into Great Lakes contaminants, chinook salmon were collected from Lake Huron (LH) and Lake Ontario (LO) and incorporated (as lyophilized fillets) into standard rat diets as 20 or 100% of the protein complement (5 or 20%, w/w diet-LH5, LH20, LO5, and LO20 diets). Final PCB concentrations in the experiment ranged from 3.15 ng/g in the control diet to 1080 ng/g in the high-dose (20%) LO diet, with maximal estimated daily consumption by the rats of 82microg PCBs/kg body wt in the LO20 dietary group. Seventeen PCB congeners, PCB 85, 99, 101, 105, 110, 118, 128, 129, 132, 138, 149, 153, 170, 177, 180, 187, and 199, occurred at >/=3.0% of the total PCBs in the fish with no major site differences. Cumulatively, these 17 congeners accounted for up to 75% of the total PCBs in the fish compared to 44 and 54% in two commercial Aroclors, 1254 and 1260, respectively. PCB 77 was the major "dioxin-like" congener in the fish, followed by PCB 126 and then PCB 169. All major dietary congeners bioaccumulated in the adipose tissue of the rats with the exception of PCB congeners 101, 110, 132, and 149. The group of 17 major congeners accounted for up to 71% of the total PCBs in adipose tissue samples collected from the rats following up to 19 weeks of diet ingestion. Of the coplanar PCB congeners, PCB 77 appeared to bioaccumulate to a lesser extent compared to PCBs 126 and 169. When comparing PCBs in the rat adipose tissue to PCB congeners in Canadian breast milk, PCBs 44, 49, 74, and 137 tended to occur in higher amounts in the human samples (contributing together 18.4 vs. 1.4% of the total PCB concentration), whereas PCB 129 occurred at higher levels in the rats (3.4 vs. 0.3% of the total PCB concentration, respectively). Although adipose tissue from the rats fed diets containing Great Lakes salmon had up to two orders of magnitude higher concentrations of PCBs compared to average human values, with the exception of some lower chlorinated congeners, similar major congeners tended to be present in both the rats in the present study and humans.
Concentrations of 24 individual PCB congeners have been measured in livers of groupers (Epinephelus marginatus) and eight shark species (Centroscymnus coelolepis, Centrophorus squamosus, Dalatias licha, Hydrolagus affinis, Deania profundorum, Centroscymnus cryptacanthus, Etmopterus princeps, Deania histricosa) collected between 1994 and 1995 from the northwest African Atlantic Ocean. The concentration range of the total PCBs was 39.4-4,723 ng/g (wet weight). The TEQs found were between 0.15 and 197 pg/g (wet weight). Analysis has revealed differences in PCB content and PCB profiles among the eight shark and grouper species. The location and depth at which the shark lives and the liver lipid content were related with their PCB liver concentrations. The PCB profiles were dominated by congeners 138 and 153, and among the most toxic congeners the order of abundance was PCB 77 > 126 > 169. Chiral PCBs 95, 132, 136, 149, and 174 were found to be racemic or nearly racemic in almost all the groupers (E. marginatus) studied. The PCB profiles of shark species and groupers were compared by principal component analysis. Samples were separated into groups according their trophic levels and geographical variations.
Large-scale poisoning occurred in central Taiwan in 1979 from ingestion of cooking oil contaminated by polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans. To determine whether in-utero exposure to these chemicals alters reproductive function, all prenatally exposed boys and appropriate controls were contacted for medical examination in 1998. Sperm of exposed children have increased abnormal morphology, reduced motility, and reduced capacity to penetrate hamster oocytes. Whether this will cause reduced fecundity, and how these effects can be extrapolated to the general population exposed to background levels of PCBs and dioxin-like chemicals, warrants further investigation.
The objective of this study was to examine the effects of gestational and lactational exposure to Aroclor 1242 (0, 10, 25, 50, and 100 mg/kg-bw) on male fertility. Doses were administered to C57BL6 female mice orally every two days from two weeks before mating, during mating, and through gestation until postnatal day 21. Male B6D2F1 offspring were examined for anogenital distance, organ development, epididymal sperm count, sperm motility, and in vitro fertility at 16 and 45 weeks of age. Stomach samples of pups nursing from PCB-treated mothers in the 50 mg/kg dose group were analyzed for PCBs and chlorobiphenylols by high resolution gas chromatography coupled with low resolution mass spectrometry. It was estimated that the nursing pups were exposed to 0.2, 0.6, 1.2, and 2.4 mg/kg/day total PCBs in the 10, 25, 50, and 100 mg/kg dose groups, respectively. This exposure level approaches the maximum FDA recommended levels for PCBs in food and breast milk. The composition of the PCBs in the stomach samples was different from the parent mixture, as there was a higher proportion of heavily chlorinated congeners, as well as chlorobiphenylols. Anogenital distance at weaning, and liver, thymus, and testes weight at 16 and 45 weeks of age were not affected by PCB exposure. Epididymal sperm velocity and linearity were significantly increased in the 25 mg/kg dose group at 16 weeks of age. Sperm count was increased by 36% in this dose group (P = 0.06). By 45 weeks of age, average sperm count in this dose group was similar to that of controls. With the exception of the 50 mg/kg dose group at 16 weeks of age, sperm fertilizing ability in vitro was significantly decreased in all PCB-exposed groups at 16 and 45 weeks of age. These results suggest that fertility in the adult mouse is susceptible to developmental exposure to Aroclor 1242 and is independent of testis weight or epididymal sperm count.
Polychlorinated biphenyls (PCBs) are worldwide pollutants and have caused hazardous effects on many animal species including humans. They have been detected in human milk and therefore exposure of newborns to PCBs is unavoidable if they are breast-fed. We present our findings on two experiments performed to test the effects of intermittent and continuous exposure of lactating rats to two different doses (80 microg and 8 microg) of Aroclor 1242 (a PCB congener) on testicular steroidogenic function of their adult male offspring. In experiment I, three groups of lactating dams received daily subcutaneous (SC) injections of either corn oil, 80 microg of Aroclor 1242 and 8 microg of Aroclor 1242 in corn oil, respectively. In experiment II, three groups of lactating dams received two SC injections per week of either corn oil or Aroclor 1242 (80 microg and 8 microg) in corn oil, respectively. Pups in all groups (n=8 per group) were weaned at day 21 and were raised on a normal diet until sacrificed at 90 days. Experiment I: Leydig cell number per testis was significantly (P<0.05) increased and the average volume of a Leydig cell was significantly (P<0.05) reduced in both groups of Aroclor-exposed rats compared to corn oil controls. Both doses of Aroclor resulted in reduced (P<0.05) serum testosterone levels compared to corn oil-treated controls. LH-stimulated testosterone production per testis and per Leydig cell was lower in Aroclor-exposed rats compared to controls. Experiment II: No changes were observed in Leydig cell size and number per testis among the three groups. Serum LH, testosterone and LH-stimulated testicular testosterone production in offspring rats of Aroclor-treated dams were not significantly different (P>.05) from the offspring of corn oil-treated dams. However, these parameters were lower in value in the offspring of dams treated with Aroclor 80 microg compared to the other two groups. LH-stimulated testosterone secretory capacity per Leydig cell was significantly lower in offspring of dams treated with Aroclor compared to controls. Serum T4 and T3 levels were not significantly different among the Aroclor-exposed and control rats in both experiments. These results demonstrate that continuous exposure of lactating mothers to 8 and 80 microg of Aroclor 1242 causes hypotrophy and malfunctioning of Leydig cells in the adult male offspring resulting in a hypoandrogenic status. Intermittent treatment of lactating mothers with 80 microg of Aroclor (but not with 8 microg of Aroclor) also produced malfunctioning of Leydig cells and a hypoandrogenic status in the absence of Leydig cell hypotrophy. However, the Aroclor 8 microg dose was ineffective to produce the above effects.
Chemical contamination of fish from the Salton Sea, a quasi-marine lake in Southern California, could adversely impact millions of birds using the Pacific Flyway and thousands of humans using the lake for recreation. Bairdiella icistia (bairdiella), Cynoscion xanthulus (orangemouth corvina), and Oreochromis spp. (tilapia) were sampled from two river mouths and two nearshore areas of the Salton Sea. Muscle tissues were analyzed for a complete suite of 14 trace metals and 53 pesticides. Fish muscle tissues had concentrations of selenium ranging between 1.89 and 2.73 microg/g wet weight. 4,4'-DDE accounted for 94% of the total DDT metabolites. Total DDTs ranged between 17.1 and 239.0 and total PCBs between 2.5 and 18.6 ng/g wet weight. PCB congeners 132, 138, 153, 168, and 180 comprised over 50% of the total PCBs. Given the potential implementation of a commercial fishing at the Salton Sea in the future, the presence of persistent organic pollutants and selenium warrants further research into the effects of these mixtures on fish populations, and on wildlife and humans consuming fish.
Polychlorinated biphenyl (PCB) concentrations were examined in 1043 Arctic vascular plant specimens comprising 31 genera and the soils they grew in. The samples were collected at 61 abandoned military and Coast Guard sites across the Canadian Arctic and Subarctic and in nine remote background locations. Genus-specific differences in PCB uptake, partitioning of PCBs among different plant tissues, and congener-specific uptake of PCBs were examined. Mean PCB concentrations and plant vs. soil regression relationships were significantly different among genera. The highest concentrations were found in Poa and Luzula and the lowest mean concentration was found in Betula. Among the genera examined, PCB concentrations in the genus Luzula exhibited the greatest increase relative to increasing soil PCB concentrations. Bioaccumulation factors were not fixed within a single genus or species, but decreased with increasing soil concentrations, suggesting that at higher levels of exposure accumulation of PCBs may be kinetically limited by redistribution processes within the plant. The accumulation of specific congeners was related to the primary mode of exposure and the octanol-air partition coefficient (K(oa)) of the congener. In plants exposed mainly to atmospheric PCBs, uptake increased with increasing K(oa), as has been reported elsewhere. By contrast, there was a negative correlation between accumulation and K(oa) in plants that were mainly exposed through direct contact with contaminated soil. Only congeners 132/153 were found at concentrations greater than predicted from their K(oa). The presence of these congeners in plants is proposed as the explanation for their predominance in terrestrial animal tissues.
Anatomy, vasculature, innervation and fluids of the male reproductive tract The Physiology of Reproduc-tion 753?/836 Methylsulfonyl metabolites of PCBs and DDE in human tissue
- B P Setchell
- D E Brooks
- E Knobil
- J Neill
Setchell, B.P., Brooks, D.E., 1988. Anatomy, vasculature, innervation and fluids of the male reproductive tract. In: Knobil, E., Neill, J. (Eds.), The Physiology of Reproduc-tion. Raven Press, New York, pp. 753?/836. Weistrand, C., Noren, K., 1997. Methylsulfonyl metabolites of PCBs and DDE in human tissue. Environ. Health Perspect. 105, 644?/649. P.-C. Hsu et al. / Toxicology 187 (2003) 117?/126 126
Analysis of organic and inorganic contaminants in Salton sea fish. Marine Pollut. Bull. 44 Effect of postnatal exposure to polychlori-nated bipheyls on adult male reproductive function. En-viron. Res. 31, 76 Á/94 Early postnatal exposure to PCBs: sperm function in rats
- R Riedel
- D Schlenk
- D Frank
- B Costa-Pierce
Riedel, R., Schlenk, D., Frank, D., Costa-Pierce, B., 2002. Analysis of organic and inorganic contaminants in Salton sea fish. Marine Pollut. Bull. 44, 403 Á/411. Sager, D.B., 1983. Effect of postnatal exposure to polychlori-nated bipheyls on adult male reproductive function. En-viron. Res. 31, 76 Á/94. Sager, D., Gigard, D., Nelson, D., 1991. Early postnatal exposure to PCBs: sperm function in rats. Environ. Toxicol. Chem. 10, 737 Á/746.
Quantitative study of the cell population of the seminiferous tubules in immature rats Sexual maturation in relation to polychlorinated aromatic hydrocarbons: Sharpe and Skak-kebaek's hypothesis revisited
- Y Clermont
- B E Perey
- H A Roels
- K Moppenbrouwers
- T Nawrot
- L Thijs
- C Vandermeulen
- G Winneke
- D Vanderschueren
- J A Staessen
Clermont, Y., Perey, B., 1957. Quantitative study of the cell population of the seminiferous tubules in immature rats. Am. J. Anat. 100, 241 Á/368. Den Hond, E., Roels, H.A., Moppenbrouwers, K., Nawrot, T., Thijs, L., Vandermeulen, C., Winneke, G., Vanderschueren, D., Staessen, J.A., 2002. Sexual maturation in relation to polychlorinated aromatic hydrocarbons: Sharpe and Skak-kebaek's hypothesis revisited. Environ. Health Perspect. 110, 771 Á/776.
In Utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodi-benzo-p -dioxin A review of the Food and Drug Administration risk analysis for polychlorinated biphenyls in fish
- T A Mably
- D L Bjerke
- R W Moore
Mably, T.A., Bjerke, D.L., Moore, R.W., 1992. In Utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodi-benzo-p -dioxin. Toxicol. Appl. Pharmacol. 114, 118 Á/126. Maxim, L.D., Harrington, L., 1984. A review of the Food and Drug Administration risk analysis for polychlorinated biphenyls in fish. Regul. Toxicol. Pharmacol. 4, 192 Á/219.
PCB congener patterns in rats consuming diets containing Great Lakes salmon: analysis of fish, diets and adipose tissue Effects of continuous and intermittent exposure of lactating mothers to Aroclor 1242 on testicular steroido-genic function in the adult male offspring
- S A Jordan
- M M Feeley
Jordan, S.A., Feeley, M.M., 1999. PCB congener patterns in rats consuming diets containing Great Lakes salmon: analysis of fish, diets and adipose tissue. Environ. Res. A 80, S207 Á/S212. Kim, I.S., Ariyaratne, H.B., Chamindrani Mendis-Handsgama, S.M., 2001. Effects of continuous and intermittent exposure of lactating mothers to Aroclor 1242 on testicular steroido-genic function in the adult male offspring. Tissue Cell 33, 169 Á/177.