Effects of xenoestrogens on male reproduction
Québec, Université du Québec, Institut National de la Recherche Scientifique, Maîtrise en sciences expérimentales de la santé, 171 p.
White previous studies have identified the presence of estrogenic substances in St. Lawrence river, along the Island of Montreal there is no information on the physiological and population consequences associated with exposure to low levels of estrogenic compounds in fish in these sites. Therefore, the objective of my first study was to assess the effects of such contaminants on male reproductive function in the spottail shiner (Notropis hudsonius). Disturbances in stages of spermatogenesis were seen in fish captured at sites having high levels of estrogenic contamination. Sperm concentration and various motility parameters were significantly lower in shiners from Ilet Vert as compared with those from Iles de la Paix (reference site). 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.
After finding that the fish from the St. Lawrence River are exposed to xenoestrogens causing male reproductive dysfunction, in the second part of my study we wanted 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 (IIet Vert). Pups were exposed via lactation and sampled on either day 21 (weaning) or day 91 (adults). Adult sperm concentrations and sperm motility parameters were ali significantly decreased in the xenoestrogen 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 proLein, 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.
The mechanism responsible for alteration in gap junctions m Sertoli cells after exposure to xenoestrogens is unknown. The objectives of the third part of my study were to determine the effects of nonylphenol on GJIC and connexin 43 (Cx43) in a murine Sertoli cell tine, TM4. 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. 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. In contrast, no effect on GJIC or Cx43 protein was observed in cells exposed to 17beta-estradiol at these concentrations. These results suggest that nonylphenol inhibits GJIC
between Sertoli cells and that this is modulated via nonestrogenic pathways.
In summary we have shown that xenoestrogens in the aquatic system can effect spermatogenesis in fish and this effect can be passed up the food chain. Also xenoestrogens like nonylphenol can have effects that are not mediated by the classical estrogen pathway.
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