Methoxychlor affects the decidual cell response of the uterus but not other progestational parameters in female rats.
The pesticide methoxychlor (MXC) is a proestrogen which is metabolized to a compound that has been shown to exhibit estrogenic activity in vivo and in vitro. Following long-term exposure of female rats to MXC, fertility is reduced and fetotoxicity is evident. However, the effects of MXC on several aspects of maternal reproductive physiology, including the decidual cell response (DCR), ovarian weight, serum progesterone levels, and corpora lutea maintenance, have not been previously described. In the present study, the ability of MXC to interfere with progestational events essential for implantation and the maintenance of pregnancy in the rat was investigated. MXC was administered to pseudopregnant rats, decidualization was induced on Day 4, and the DCR and related parameters were evaluated following euthanasia on Day 9. DCR induction during estrone administration served as a positive control. MXC inhibited decidualization in a dose-dependent manner: while 100 mg/kg/day had no effect, doses of 200, 300, 400, and 500 mg/kg/day produced incremental inhibition of the response. No effects of MXC on ovarian weight, serum progesterone levels, or number of corpora lutea were observed. Estrone also inhibited the DCR in a dose-dependent manner. The data suggest that the anti-fertility effect of MXC is mediated by a suppression of decidualization and that such suppression, which is characteristic of estrogenic compounds, is a direct uterine effect. In the DCR model system, the estrogenic activity of MXC is 1/20,000 times the activity of estrone.
D000818:Animals; D003656:Decidua / Q000187:drug effects*; D004622:Embryo, Mammalian / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005298:Fertility / Q000187:drug effects; D008731:Methoxychlor / Q000378:metabolism / Q000633:toxicity*; D010053:Ovary / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D014599:Uterus / Q000187:drug effects
D004967:Estrogens; D008731:Methoxychlor