Effects of endocrine-disrupting contaminants on amphibian oogenesis: methoxychlor inhibits progesterone-induced maturation of Xenopus laevis oocytes in vitro.
There is currently little evidence of pollution-induced endocrine dysfunction in amphibia, in spite of widespread concern over global declines in this ecologically diverse group. Data regarding the potential effects of endocrine-disrupting contaminants (EDCs) on reproductive function in amphibia are particularly lacking. We hypothesized that estrogenic EDCs may disrupt progesterone-induced oocyte maturation in the adult amphibian ovary, and tested this with an in vitro germinal vesicle breakdown assay using defolliculated oocytes from the African clawed frog, Xenopus laevis. While a variety of natural and synthetic estrogens and xenoestrogens were inactive in this system, the proestrogenic pesticide methoxychlor was a surprisingly potent inhibitor of progesterone-induced oocyte maturation (median inhibitive concentration, 72 nM). This inhibitory activity was specific to methoxychlor, rather than to its estrogenic contaminants or metabolites, and was not antagonized by the estrogen receptor antagonist ICI 182,780, suggesting that this activity is not estrogenic per se. The inhibitory activity of methoxychlor was dose dependent, reversible, and early acting. However, washout was unable to reverse the effect of short methoxychlor exposure, and methoxychlor did not competitively displace [3H]progesterone from a specific binding site in the oocyte plasma membrane. Therefore, methoxychlor may exert its action not directly at the site of progesterone action, but downstream on early events in maturational signaling, although the precise mechanism of action is unclear. The activity of methoxychlor in this system indicates that xenobiotics may exert endocrine-disrupting effects through interference with progestin-regulated processes and through mechanisms other than receptor antagonism.
Pickford
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DB
Division of Physiology, Pharmacology and Toxicology, School of Biological Sciences, University of Manchester, Manchester, UK.
Morris
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ID
D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004967:Estrogens / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity*; D008731:Methoxychlor / Q000633:toxicity*; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development; D009866:Oogenesis / Q000187:drug effects*; D011374:Progesterone / Q000502:physiology; D013997:Time Factors; D015262:Xenobiotics / Q000633:toxicity; D014982:Xenopus laevis / Q000254:growth & development*
D004785:Environmental Pollutants; D004967:Estrogens; D007306:Insecticides; D015262:Xenobiotics; D011374:Progesterone; D008731:Methoxychlor