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Hua Wang,
Yan-Li Ji,
Qun Wang,
Xian-Feng Zhao,
Huan Ning, Ping Liu,
Cheng Zhang,
Tao Yu,
Ying Zhang,
Xiu-Hong Meng,
De-Xiang Xu
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ABSTRACT: Lead (Pb) is a testicular toxicant. In the present study, we investigated the effects of maternal Pb exposure during lactation on testicular development and steroidogenesis in male offspring. Maternal mice were exposed to different concentration of lead acetate (200 or 2000 ppm) through drinking water from postnatal day (PND) 0 to PND21. As expected, a high concentration of Pb was measured in the kidneys and liver of pups whose mothers were exposed to Pb during lactation. In addition, maternal Pb exposure during lactation elevated, to a less extent, Pb content in testes of weaning pups. Testis weight in weaning pups was significantly decreased when maternal mice were exposed to Pb during lactation. The level of serum and testicular T was reduced in Pb-exposed pups. The expression of P450scc, P450(17α) and 17β-HSD, key enzymes for T synthesis, was down-regulated in testes of weaning pups whose mothers were exposed to Pb during lactation. Interestingly, the level of serum and testicular T remained decreased in adult offspring whose mothers were exposed to Pb during lactation. Importantly, the number of spermatozoa was significantly reduced in Pb-exposed male offspring. Taken together, these results suggest that Pb could be transported from dams to pups through milk. Maternal Pb exposure during lactation persistently disrupts testicular development and steroidogenesis in male offspring. Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology 07/2012; · 2.48 Impact Factor
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Hua Wang,
Su-Fang Wang,
Huan Ning,
Yan-Li Ji,
Cheng Zhang,
Ying Zhang,
Tao Yu,
Xing-Hao Ma,
Xian-Feng Zhao,
Qun Wang, Ping Liu,
Xiu-Hong Meng,
De-Xiang Xu
[show abstract]
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ABSTRACT: Within the last decade, numerous epidemiological studies have demonstrated that endocrine disruptors are a possible cause for a decline in semen quality. Cypermethrin is a widely used pyrethroid insecticide, but little is known about its potentially adverse effects on male reproduction. In the present study, we investigated the effects of maternal cypermethrin exposure during lactation on testicular development and spermatogenesis in male offspring. Maternal mice were administered with cypermethrin (25 mg/kg) by gavage daily from postnatal day 0 (PND0) to PND21. Results showed that the weight of testes at PND21 was significantly decreased in pups whose mothers were exposed to cypermethrin during lactation. Maternal cypermethrin exposure during lactation markedly decreased the layers of spermatogenic cells, increased the inside diameter of seminiferous tubules, and disturbed the array of spermatogenic cells in testes of pups at PND21. In addition, maternal cypermethrin exposure during lactation markedly reduced mRNA and protein levels of testicular P450scc, a testosterone (T) synthetic enzyme. Correspondingly, the level of serum and testicular T at weaning was significantly decreased in pups whose mothers were exposed to cypermethrin during lactation. Although the expression of testicular T synthetic enzymes and serum and testicular T in adulthood had restored to control level, the decreased testicular weight and histological changes were irreversible. Importantly, the number of spermatozoa was significantly decreased in adult male offspring whose mothers were exposed to cypermethrin during lactation. In conclusion, maternal cypermethrin exposure during lactation permanently impairs testicular development and spermatogenesis in male offspring, whereas cypermethrin-induced endocrine disruption is reversible.
Environmental Toxicology 08/2011; 26(4):382-94. · 2.41 Impact Factor
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Yan-Li Ji,
Hua Wang, Ping Liu,
Xian-Feng Zhao,
Ying Zhang,
Qun Wang,
Heng Zhang,
Cheng Zhang,
Zi-Hao Duan,
Can Meng,
De-Xiang Xu
[show abstract]
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ABSTRACT: Cadmium (Cd) is a testicular toxicant and endocrine disruptor. In the present study, we investigated the effects of maternal Cd exposure during the late pregnant period on testicular development and steroidogenesis in male offspring. Pregnant mice were injected intraperitoneally with CdCl(2) (0.5mg/kg) daily from gestational day (gd) 13 to gd 17. As expected, fetal weight and crown length were significantly decreased in pups whose mothers were exposed to Cd. Importantly, absolute and relative weights of testes were significantly decreased in male fetuses. In addition, maternal Cd exposure during pregnancy markedly reduced serum T level and downregulated the expression of steroidogenic acute regulatory (StAR) protein, P450scc, P45017α and 17β-HSD in testes of male fetuses. Interestingly, the level of serum and testicular T at adulthood remained decreased in male offspring of Cd-exposed mice. Correspondingly, the expression of testicular P450scc was downregulated in male adult offspring whose mothers were exposed to Cd during pregnancy. Fertility analysis found that the number of live fetuses per litter in F2 generation was significantly decreased in Cd-treated group. Additional experiment showed that placental Cd level was increased about 750 folds in dams injected with Cd. However, only traces of blood Cd was measured in fetuses whose mothers were exposed to Cd during the late pregnant period. Taken together, these results suggest that placenta could deter most of Cd from passing from dams to fetuses. The impairments on testicular steroidogenesis in male offspring could not be attributed to a direct action of Cd on fetal testes.
Toxicology Letters 05/2011; 205(1):69-78. · 3.23 Impact Factor
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ABSTRACT: Fenvalerate is a potential endocrine disruptor. Several studies have demonstrated that fenvalerate disrupts testosterone (T) synthesis in testes. T and estradiol (E(2)) are de novo synthesized in the developing brain. Thus, the aim of the present study was to investigate the effects of pubertal fenvalerate exposure on the synthesis of T and E(2) and the expression of androgen receptor (AR) and estrogen receptors (ERs) in cerebral cortex. CD-1 mice were orally administered daily with either vehicle or fenvalerate (7.5 or 30 mg/kg) from postnatal day (PND) 28 to PND56. The level of T and E(2) in cerebral cortex was significantly decreased in males exposed to fenvalerate. In agreement with the decrease in T and E(2) syntheses, the expression of 17β-HSD, a key enzyme for T synthesis, was significantly reduced in cerebral cortex of fenvalerate-exposed males. Conversely, in females, the expression of 17β-HSD in cerebral cortex was mildly up-regulated by fenvalerate and the level of T and E(2) was mildly increased. Pubertal fenvalerate exposure had no effect on the expression of StAR, P450(17α) and P450scc, the key enzymes for T synthesis, and P450 aromatase, the key enzyme for E(2) synthesis, in cerebral cortex of males and females. Interestingly, the expression of AR in cerebral cortex was up-regulated in male and female mice exposed to fenvalerate, whereas pubertal fenvalerate exposure did not affect the level of ERα and ERβ in cerebral cortex. Taken together, these results suggest that pubertal fenvalerate exposure disrupts T and E(2) synthesis and the expression of AR in cerebral cortex. These changes of steroid status in the developing brain might be deleterious for neurobehavioral development.
Toxicology Letters 03/2011; 201(2):181-9. · 3.23 Impact Factor
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ABSTRACT: In human and rodent models, endocrine disrupting chemicals (EDCs) interfere with the development of cognition and behaviors. Fenvalerate is a potential EDC. The purpose of this study was to examine whether pubertal fenvalerate exposure altered behavioral development. Mice were orally administered with either vehicle or fenvalerate (7.5 or 30 mg/kg/day) from postnatal day (PND) 28 to PND56. Learning and memory were assessed by Morris Water Maze. Aggressive performance was evaluated by aggressive behavior test. Anxiety-related activities were detected by three tests: open-field, plus-maze and black-white alley. Sensorimotor function was analyzed using beam walking and tightrope. Results found that the impairment for spatial learning and memory was more severe in fenvalerate-exposed female mice than in male mice. In addition, pubertal fenvalerate exposure inhibited aggressive behavior in males. Moreover, pubertal fenvalerate exposure increased anxiety activities in females. Altogether, these results suggest that pubertal fenvalerate exposure impairs spatial cognition and behavioral development in a gender-dependent manner. These findings identify fenvalerate as candidate environmental risk factors for cognitive and behavioral development, especially in the critical period of development.
Toxicology Letters 03/2011; 203(3):245-51. · 3.23 Impact Factor
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ABSTRACT: Fenvalerate has a potentially adverse effect on male reproduction and spermatogenesis, whereas the precise mechanism remains obscure. The present study investigated the effects of fenvalerate on germ cell apoptosis in testes. Adult male mice were administered with fenvalerate (15 or 60 mg/kg) by gavage for 28 days. Germ cell apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). The number of TUNEL+ germ cells per tubule and the percentage of tubules with TUNEL+ germ cells were significantly increased in testes of mice treated with fenvalerate in a dose-dependent manner. TUNEL+ germ cells were observed mainly in stages VII-VIII and also stages IX-XII seminiferous tubules in testes. Additional experiments showed that fenvalerate increased the level of active caspase-8 and caspase-3 in testes. In addition, fenvalerate upregulated the expression of Fas and FasL in testes. No significant difference on the expression of Bcl-2 and Bax in testes was observed between fenvalerate-treated mice and controls. Fenvalerate did not affect the leakage of cytochrome c from mitochondria into cytoplasm. In addition, fenvalerate did not cause the activation of caspase-9 in testes. Taken together, these results suggest that fenvalerate induces germ cell apoptosis in testes through the Fas/FasL signaling pathway.
Archive für Toxikologie 01/2011; 85(9):1101-8. · 4.67 Impact Factor
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ABSTRACT: Bisphenol A (BPA) is a potential endocrine disruptor and testicular toxicant. An earlier study showed that BPA-induced germ cell apoptosis through the Fas/FasL apoptotic pathway. In the present study, we aimed to investigate whether the mitochondrial pathway is also involved in the process of BPA-mediated germ cell apoptosis in testes. Male mice were administered with BPA (160 or 480 mg/kg) by gavage daily from postnatal day 35 (PND35) to PND49. Germ cell apoptosis in testes was determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). As expected, the number of TUNEL+ germ cells per tubule and the percentage of tubules with TUNEL+ germ cells were significantly increased in testes of mice treated with BPA during puberty. TUNEL+ germ cells were observed mainly in stages VII-VIII seminiferous tubules in testes. An increase in the level of Fas and FasL was observed in testes of mice exposed to BPA during puberty. In addition, pubertal BPA exposure evoked the activation of caspase-8 and caspase-3 in testes. Interestingly, pubertal BPA exposure also caused the translocation of cytochrome c from mitochondria into cytosol. In addition, pubertal BPA exposure upregulated the level of Bax and active caspase-9 in testes. Taken together, these results suggest that pubertal BPA exposure induces germ cell apoptosis in testes through not only the Fas/FasL signaling pathway but also the mitochondrial apoptotic pathway.
Toxicology Letters 11/2010; 199(2):129-35. · 3.23 Impact Factor
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Heng Zhang,
Hua Wang,
Qun Wang,
Xian-Feng Zhao, Ping Liu,
Yan-Li Ji,
Huan Ning,
Tao Yu,
Cheng Zhang,
Ying Zhang,
Xiu-Hong Meng,
De-Xiang Xu
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ABSTRACT: Fenvalerate, a pyrethroid insecticide used worldwide, has been shown to have a potentially adverse effect on male reproduction. Our earlier study showed that maternal fenvalerate exposure during lactation impaired testicular development in male offspring. In this study, we investigated the effects of pubertal and early adult exposure to fenvalerate on steroidogenesis and spermatogenesis in mice. Male mice were administered fenvalerate (60 mg/kg) by gavage daily from postnatal day 35 (PND35) to PND63. Results showed that sperm count was significantly decreased in fenvalerate-treated mice. In addition, fenvalerate markedly decreased the layers of spermatogenic cells, disturbed the array of spermatogenic cells and increased the number of apoptotic cells in testes. The adverse effects of fenvalerate on male reproduction seemed to be associated with a decrease in serum and testicular testosterone (T). Although pubertal and early adult exposure to fenvalerate had little effect on the number of Leydig cells in testes, mRNA and protein levels of testicular T biosynthetic enzymes including P450(17alpha) and P450scc were significantly downregulated in fenvalerate-treated mice. In conclusion, pubertal and early adult fenvalerate exposure induces a deleterious effect on steroidogenesis and spermatogenesis in adulthood. The decreased testicular T synthesis partially contributes to fenvalerate-induced impairment on spermatogenesis.
Journal of Applied Toxicology 05/2010; 30(4):369-77. · 2.48 Impact Factor
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Heng Zhang,
Hua Wang,
Yan-Li Ji,
Ying Zhang,
Tao Yu,
Huan Ning,
Cheng Zhang,
Xian-Feng Zhao,
Qun Wang, Ping Liu,
De-Xiang Xu
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ABSTRACT: Fenvalerate, a widely used pyrethroid insecticide, has been associated with poor semen quality. As yet, little is known about the effects of prenatal fenvalerate exposure on testicular development. The present study investigated the effects of prenatal fenvalerate exposure on testicular development and spermatogenesis. The pregnant mice were administered fenvalerate (30 mg/kg) by gavage daily from gestational day (gd) 13 to gd 18. The weights of testes and epididymides were significantly decreased in mice whose mothers were exposed to fenvalerate during pregnancy. Importantly, maternal fenvalerate exposure during pregnancy markedly decreased the number of mature seminiferous tubules (stages VII and VIII) in testes of adult male offspring. In addition, maternal fenvalerate exposure during pregnancy significantly reduced the number of epididymal spermatozoa in adult male offspring. Additional experiments showed that the level of serum testosterone (T) was significantly decreased in male fetuses whose mothers were exposed to fenvalerate during pregnancy. Correspondingly, mRNA and protein levels of P450(17alpha), a T synthetic enzyme, were significantly decreased in fetal testes. Moreover, the disruptive effect of prenatal fenvalerate exposure on testicular T synthesis was irreversible. In conclusion, prenatal fenvalerate exposure irreversibly impairs testicular development and spermatogenesis at least into early adulthood.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 02/2010; 48(5):1160-9. · 2.99 Impact Factor
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Hua Wang,
Qun Wang,
Xian-Feng Zhao, Ping Liu,
Xiu-Hong Meng,
Tao Yu,
Yan-Li Ji,
Heng Zhang,
Cheng Zhang,
Ying Zhang,
De-Xiang Xu
Archive für Toxikologie 12/2009; · 4.67 Impact Factor
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ABSTRACT: Lipopolysaccharide (LPS)-induced intrauterine infection has been associated with neurodevelopmental injury in rodents. The purpose of the present study was to analyze the dynamic changes of neurobehaviors in mice whose mothers were exposed to LPS during pregnancy. The pregnant mice were intraperitoneally (i.p.) injected with LPS (8 microg/kg) daily from gestational day (gd) 8 to gd 15. A battery of neurobehavioral tasks was performed in mice at postnatal day (PND) 70, 200, 400 and 600. Results showed that the spatial learning and memory ability, determined by radial six-arm water maze (RAWM), were obviously impaired in two hundred-day-old female mice and four hundred-day-old male mice whose mothers were exposed to LPS during pregnancy. Open field test showed that the number of squares crossed and peripheral time, a marker of anxiety and exploration activity, were markedly increased in two hundred-day-old female mice following prenatal LPS exposure. In addition, prenatal LPS exposure significantly shortened the latency to the first grid crossing in six hundred-day-old female offspring. Moreover, sensorimotor impairment in the beam walking was observed in two hundred-day-old female mice whose mothers were exposed to LPS during pregnancy. Species-typical behavior examination showed that prenatal LPS exposure markedly increased weight burrowed in seventy-day-old male offspring and six hundred-day-old female offspring. Correspondingly, prenatal LPS exposure significantly reduced weight hoarded in two hundred-day-old female offspring. Taken together, these results suggest that prenatal LPS exposure induces neurobehavioral impairments at adulthood in an age- and gender-dependent manner.
Toxicology Letters 11/2009; 192(2):245-51. · 3.23 Impact Factor
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Yan-Li Ji,
Hua Wang, Ping Liu,
Qun Wang,
Xian-Feng Zhao,
Xiu-Hong Meng,
Tao Yu,
Heng Zhang,
Cheng Zhang,
Ying Zhang,
De-Xiang Xu
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ABSTRACT: Cadmium (Cd) is a well-known testicular toxicant. However, the effects of pubertal Cd exposure on testicular development and spermatogenesis remained to be elucidated. The present study investigated the effects of pubertal Cd exposure on testicular development and spermatogenesis. Male CD-1 mice were intraperitoneally injected with CdCl(2) (1mg/kg) daily from postnatal day 35 (PND35) to PND70. As expected, pubertal Cd exposure significantly decreased the number of spermatozoa in epididymides. In addition, pubertal Cd exposure markedly reduced the weights of testes, epididymides and prostate and seminal vesicle in adult mice. A significant decrease in serum and testicular testosterone (T) was observed in mice exposed to Cd during puberty. Moreover, pubertal Cd exposure markedly reduced mRNA and protein levels of testicular StAR, P450scc, P450(17alpha) and 17beta-HSD. Taken together, these results suggest that the decreased testicular T synthesis might partially contribute to pubertal Cd-induced impairment on testicular development and spermatogenesis in mice.
Reproductive Toxicology 11/2009; 29(2):176-83. · 3.23 Impact Factor
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Hua Wang,
Qun Wang,
Xian-Feng Zhao, Ping Liu,
Xiu-Hong Meng,
Tao Yu,
Yan-Li Ji,
Heng Zhang,
Cheng Zhang,
Ying Zhang,
De-Xiang Xu
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ABSTRACT: Cypermethrin is a widely used synthetic pyrethroid insecticide. Previous studies showed that cypermethrin significantly decreased the fertility and reduced the number of implantation sites and viable fetuses in females impregnated by males exposed to cypermethrin. As yet, little is known about the mechanism of cypermethrin-induced reproductive toxicity. In the present study, we investigated the effects of cypermethrin exposure during puberty on steroidogenesis in mice. Young male mice were administered with cypermethrin (25 mg/kg) by gavage daily from postnatal day (PND) 35 to PND70. Results showed that the level of serum and testicular testosterone (T) was markedly decreased in cypermethrin-treated mice. Additional experiment showed that cypermethrin exposure during puberty markedly downregulated mRNA level of steroidogenic acute regulatory protein (StAR) in testes. Correspondingly, protein level of testicular StAR was significantly decreased in cypermethrin-treated mice. Cypermethrin exposure during puberty did not affect the number of Leydig cells in testes. Although cypermethrin exposure during puberty did not affect the weight of testes and epididymides, the number of sperm in the cauda epididymides was significantly decreased in cypermethrin-treated mice. Taken together, these results indicate that cypermethrin exposure during puberty significantly disrupts T synthesis via downregulating the expression of testicular StAR. The decreased T synthesis might be associated with cypermethrin-induced impairment in spermatogenesis in mice.
Archive für Toxikologie 10/2009; 84(1):53-61. · 4.67 Impact Factor
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Heng Zhang,
Hua Wang,
Yan-Li Ji,
Huan Ning,
Tao Yu,
Cheng Zhang,
Ying Zhang,
Xian-Feng Zhao,
Qun Wang, Ping Liu,
Xiu-Hong Meng,
De-Xiang Xu
[show abstract]
[hide abstract]
ABSTRACT: Fenvalerate, a widely used synthetic pyrethroid insecticide, has been associated with poor semen quality in human being. However, little is known about the effects of lactational fenvalerate exposure on testicular development and spermatogenesis. The purpose of the present study was to investigate the effects of maternal fenvalerate exposure during lactation on testicular development and spermatogenesis in male offspring. Maternal mice were administered with fenvalerate (60 mg/kg) by gavage daily from postnatal day (PND) 0 to PND21. Lactational fenvalerate exposure markedly decreased the absolute and relative weights of testes and increased the number of apoptotic cells in testes of pups at weaning. Histological examinations showed abnormal seminiferous tubules with large vacuoles or complete spermatogenic failure in testes of fenvalerate-treated mice at weaning. Additional experiment showed that lactational fenvalerate exposure markedly reduced mRNA and protein levels of testicular P450scc, a testosterone (T) synthesis enzyme. Consistent with down-regulation of testicular P450scc, the level of serum and testicular T at weaning was significantly decreased in pups whose mothers were exposed to fenvalerate during lactation. Although the expression of testicular P450scc and serum and testicular T in adulthood restored to control level, the decreased weight of testes and histological changes were irreversible. Importantly, the percentage of mature seminiferous tubules (stages VII and VIII) and the number of spermatozoa were obviously decreased in adult male mice whose mothers were exposed to fenvalerate during lactation. Taken together, these results suggest that lactational fenvalerate exposure permanently impairs testicular development and spermatogenesis.
Toxicology Letters 09/2009; 191(1):47-56. · 3.23 Impact Factor
