[Show abstract][Hide abstract] ABSTRACT: Oxidative compounds have been demonstrated to decrease the fertilization capability and viability of offspring of treated spermatozoa. As estrogen and its hydroxylated metabolites readily undergo redox cycling, this study was undertaken to determine if estrogens and other oxidants could damage DNA and impair sperm function. Sperm was preexposed to either 17beta-estradiol (E2), 4-hydroxyestradiol (4OHE2) or the oxidant t-butyl hydroperoxide (t-BOOH), and allowed to fertilize untreated eggs. The fertilization rates and development of the larvae were assessed, as well as the amount of 8-oxodeoxyguanosine (8-oxodG) as an indication of oxidative DNA damage. All compounds caused significant decreases in fertilization and increases in pathological abnormalities in offspring, with 4OHE2 being the most toxic. Treatment with 4OHE2 caused a significant increase of 8-oxodG, but E2 failed to show any effect. Pathological abnormalities were significantly correlated (r(2)=0.44, p< or =0.05) with 8-oxodG levels in sperm treated with t-BOOH and 4OHE2, but not E2. 8-OxodG levels also were somewhat weakly correlated with impaired fertilization in 4OHE2-treated sperm (r(2)=0.33, p< or =0.05). The results indicate that biotransformation of E2 to 4OHE2 enhances oxidative damage of DNA in sperm, which can reduce fertilization and impair embryonic development, but other mechanisms of action may also contribute to these effects.
Science of The Total Environment 02/2009; 407(7):2209-15. DOI:10.1016/j.scitotenv.2008.12.054 · 4.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies in extracts of sediments surrounding municipal outfalls off the coast of California, USA and effluents of New York City, NY, USA indicated the UV-filtering agent, oxybenzone (CAS# 131-57-7; benzophenone-3) as a potential estrogen. The effects of oxybenzone on estrogenic activity and reproduction were evaluated using a 14-day juvenile rainbow trout assay for plasma vitellogenin and a subsequent 21-day Japanese medaka reproduction assay. Significant induction of vitellogenin was observed in the rainbow trout at the 1000 microg/L nominal concentration (749 microg/L median measured value) of oxybenzone which was approximately 75 times greater than the concentrations observed in previous wastewater effluent. Vitellogenin induction was also observed in the 1000 microg/L nominal concentration (620 microg/L median measured) of oxybenzone in male Japanese medaka (Oryzias latipes) after 21 days of exposure. The number of eggs produced per female per day exposed to the same concentration (620 microg/L) were significantly lower after 7 days, but returned to control values after 21 days. Fertilized eggs were then monitored for 20 days to assess hatching success. The overall percentage of fertilized eggs collected during the 21-day exposure that hatched was significantly lower in the 620 microg/L oxybenzone concentration. There was also a temporal effect at this concentration as egg viability (percentage of fertilized eggs that hatched) was diminished 13-15 days after eggs were collected. All three oxybenzone concentrations (16, 132, and 620 microg/L) and the 50 ng/L estradiol positive control showed reduced hatching of eggs at day 15, and the 132 and 620 microg/L oxybenzone concentrations diminished the percentage of eggs that hatched on days 13-15. These data indicate that the UV-filter oxybenzone alters endocrine or reproduction endpoints in two fish species, but at concentrations significantly higher than those measured in the environment.
[Show abstract][Hide abstract] ABSTRACT: Male and female hornyhead turbot (Pleuronichthys verticalis) were exposed to four concentrations (0, 0.75, 14.7 and 46.5 ng/g dry weight) of E2-amended sediment for 7 days. Sediment-derived E2 was bioavailable to the flatfish, though the route of uptake was unclear. A concentration of 46.5 ng/g E2 in sediment led to a significant increase in vitellogenin concentrations in the plasma in both sexes after 7 days of exposure. Though plasma E2 concentrations increased significantly in males at sediment E2 concentrations of 0.75 ng/g dry weight and above, a dose-dependent increase was not observed. There was also no correlation between sediment E2 concentrations, plasma E2 concentrations, and oxidative DNA damage in male gonads. The results suggest that the DNA damage previously seen in the gonads of feral hornyhead turbot at a sewage outfall is likely not caused by acute exposure to exogenous E2 from sediments.
Marine Environmental Research 08/2008; 66(1):111-2. DOI:10.1016/j.marenvres.2008.02.039 · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A number of studies have indicated widespread reproductive endocrine disruption in wild fish populations. A number of laboratory studies have been conducted to determine the sources and to elucidate potential mechanisms of the disruption. This review explores the varied mechanisms of estrogenic and antiandrogenic effects in fish including effects at the steroid receptor level, effects on steroid synthesis, distribution, and excretion, actions up the hypothalamus-pituitary-gonad axis, as well as indirect mechanisms including thyroid and growth hormone disruption. Consequences of reproductive endocrine disruption will be touched on including non-reproductive responses such as impaired gene regulation, effects of unscheduled protein synthesis and DNA damage, and reproductive responses such as intersex, sex reversal and reproductive failure.
International review of cell and molecular biology 02/2008; 267:207-52. DOI:10.1016/S1937-6448(08)00605-9 · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Seasonal changes in developmental stages, condition factor (CF), gonadosomatic index, and plasma vitellogenin (Vtg) concentrations in male and female hornyhead turbot were examined at the wastewater outfall (T1) of the Orange County Sanitation District, and two farfield sites T11 (7.7 km northwest of the outfall) and Dana Point (35 km south of the outfall) between February 2005 and May 2006. Fish collected from the three sites exhibited male-oriented sex ratios. With few exceptions, developmental stages, CF, and GSI of both genders and plasma Vtg concentrations of females were not significantly different in samples collected from different sites at the same sampling period. More advanced gonad developmental stages and higher plasma Vtg concentrations in females were observed in August, indicating the seasonality of the reproductive cycle for this species. Plasma Vtg concentrations in males were observed in all of the sampling sites with the highest prevalence at T11 relative to T1 and Dana Point. The Vtg expression in males from the three sampling sites indicated widespread exposure to estrogenic compounds in waters of coastal California. However, the histopathological and reproductive relevance of the responses appeared to be insignificant and may not affect the population in these locations.
[Show abstract][Hide abstract] ABSTRACT: Estrogenic activity in fish has primarily been evaluated using vitellogenin (vtg) expression in male and juvenile animals. Although the response has been widespread in field and laboratory studies, the relevance of the response to higher level adverse effects, particularly in the field, is less than clear. Previous evaluations of vtg within flatfish species collected near the Orange County Sanitation District (OCSD) outfall and stations as far as 7.7 km down current indicated bioavailable estrogens within demersal flatfish populations. In order to evaluate the persistence of estrogenic activity and relationships to reproduction and development, fish were sampled in the winter and summer of 2003 and 2004 at the outfall and a reference location. Vtg, plasma estradiol (E2) concentrations, gonadosomatic indices (GSI), sperm DNA damage, development, and gender ratios were measured in English Sole (Pleuronectes vetulus) and Hornyhead Turbot (Pleuronichthys verticalis). Variable levels of vtg were continually observed in the plasma samples of fish collected at both locations. Vtg expression and plasma E2 levels were significantly correlated in females. A positive relationship was demonstrated between plasma E2 levels and sperm DNA damage. Rather than an expected feminization of populations, a trend toward masculinization was observed particularly at the OCSD outfall, as indicated by gender ratios and significantly higher GSI in males versus females. These results are consistent with previous studies showing vtg expression in male flatfish, but no alteration in overall flatfish abundance at the sampled sites.