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There is limited information on the physiological consequences associated with exposure to xenoestrogens under field conditions. The objectives of this study were to determine the presence of estrogenic chemicals in the St. Lawrence River and their effects on male reproduction in the spottail shiner (Notropis hudsonius). Hepatic vitellogenin (VTG) mRNA levels in immature shiners indicate extensive estrogenic contamination spanning almost 50 km both upstream and downstream from the island of Montreal. Stages of spermatogenesis were assessed in fish captured at sites having varying levels of estrogenic contamination. In control fish, 95% had testis of either stage IV (50%) or stage V (45%) of spermatogenesis. At Ile Dorval, where VTG mRNA levels are moderate, fish had testes of stage III (38%) and IV (45%) and only 15% of fish were at spermatogenic stage V. In contrast, at Ilet Vert and Ile Beauregard, located in the sewage effluent plume from the City of Montreal and where hepatic VTG mRNA levels are high in fish, none of the fish were at stage V and 8% of fish at Ilet Vert were at stage II of development. Sperm concentration and various motility parameters were significantly lower in shiners from Ilet Vert as compared with those from Iles de la Paix (reference). Histological analyses of testes revealed that more than one-third of the fish captured at sites with the highest estrogenic contamination displayed intersex, a condition in which ovarian follicles were developing within the testis. These data indicate that there is significant estrogenic contamination in the St. Lawrence River that is associated with impaired reproductive function in male fish.

Little information exists on the transfer of endocrine-disrupting effects through the food chain. The transfer of chemicals, particularly from the aquatic ecosystem, that can cause such effects on fish-eating predators must be established. Fish from the St. Lawrence River are exposed to xenoestrogens causing male reproductive dysfunction. The objective of this study was to determine if lactational exposure to contaminated fish could alter the development of the male reproductive system in rats. Three experimental groups were used: rats (dams) gavaged with (a) distilled water (control), or (b) homogenized fish from a reference site (Iles de la Paix) or (c) homogenized fish from a xenoestrogen-contaminated site (Ilet Vert). Pups were exposed via lactation and sampled on either day 21 (weaning) or day 91 (adults). There was no effect on the body weights or in the male reproductive organ weights between groups except for adult epididymal weight, which was significantly decreased in the xenoestrogen group. Adult sperm concentrations and sperm motility parameters were all significantly decreased in the xeonestrogen group as compared to the reference and control groups. Furthermore, the distribution of stages of spermatogenesis was altered in the xenoestrogen group, indicating an effect on the kinetics of spermatogenesis. Immunoreactivity of connexin43 (Cx43), a gap-junctional protein, was markedly decreased in the seminiferous epithelium of the xenoestrogen group, suggesting that the intercellular coordination of testicular function may be affected. These data indicate that contaminants from xenoestrogen environments may pass through the food chain and exert effects on male reproductive functions.

Endocrine-disrupting chemicals are exogenous compounds that mimic or inhibit the action of estrogens or other hormones. Nonylphenol, an environmental contaminant distributed along the St. Lawrence River, has been reported to act as a weak estrogen. Previous studies from our laboratory have shown that rats that were fed fish taken from nonylphenol contaminated sites have altered spermatogenesis and decreased sperm count. The mechanism responsible for this effect is unknown. Gap junctional intercellular communication (GJIC) in the testis is critical for coordinating spermatogenesis. The objectives of the study were to determine the effects of nonylphenol on GJIC and connexin 43 (Cx43) in a murine Sertoli cell line, TM4. Cells were exposed for 24 h to different concentrations (1 to 50 microM) of either nonylphenol or 17beta-estradiol. GJIC was determined using a microinjection approach in which Lucifer yellow was injected directly into a single cell, and GJIC was assessed 3 min postinjection. Nonylphenol exposure decreased GJIC between adjacent cells by almost 80% relative to controls. A significant concentration-dependent reduction in GJIC was observed at nonylphenol concentrations between 1 and 50 microM. Cx43 immunofluorescent staining was reduced at both 10 and 50 microM doses of nonylphenol. Cx43 phosphorylation, as determined by Western blot analysis, was reduced at both 10 and 50 microM concentrations, which may explain, at least in part, the inhibition of GJIC. In contrast, no effect on GJIC or Cx43 protein was observed in cells exposed to 17beta-estradiol at these concentrations. Cx43 has been reported to be phosphorylated via the p38-mitogen-activated protein kinase (MAPK) pathway. P38-MAPK activity was assessed in both control and nonylphenol-exposed cells. A dose-dependent decrease in p38-MAPK activity was observed in nonylphenol-exposed Sertoli cells. Protein kinase C activity was also measured and was not influenced by nonylphenol. These results suggest that nonylphenol inhibits GJIC between Sertoli cells and that this is modulated via nonestrogenic pathways.