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 dysfuncti on in amphibia, in spite of widespread concern over global declines in this ecologically diverse group. Data regarding the potential effects of endocr ine-disrupting contaminants (EDCs) on reproductive function in amphibia are particularly lacking. We hypothesized that estrogenic EDCs may disrupt pro gesterone-induced oocyte maturation in the adult amphibian ovary, and teste d this with an in vitro germinal vesicle breakdown assay using defolliculat ed oocytes from the African clawed frog, Xenopus laevis. While a variety of natural and synthetic estrogens and xenoestrogens were inactive in this sy stem, the proestrogenic pesticide methoxychlor was a surprisingly potent in hibitor of progesterone-induced oocyte maturation (median inhibitive concen tration, 72 nM). This inhibitory activity was specific to methoxychlor, rat her than to its estrogenic contaminants or metabolites, and was not antagon ized 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 unab le to reverse the effect of short methoxychlor exposure, and methoxychlor d id not competitively displace [H-3]progesterone from a specific binding sir e in the oocyte plasma membrane. Therefore, methoxychlor may exert its acti on 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 xen obiotics may exert endocrine-disrupting effects through interference with p rogestin-regulated processes and through mechanisms other than receptor ant agonism.