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AUTIFERTILITY EFFECT OF METHOXYCHLOR IN FEMALE RATS: DOSE AND TIME DEPENDENT BLOCKADE OF PREGNANCY
Citation:
Cummings, A. AND L. Gray, Jr. AUTIFERTILITY EFFECT OF METHOXYCHLOR IN FEMALE RATS: DOSE AND TIME DEPENDENT BLOCKADE OF PREGNANCY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/050 (NTIS PB90100918).
Description:
Long-term exposure to methoxychlor (MXC) an estrogenic pesticide, produces infertility in rats, and short-term exposure blocks the decidual cell response (DCR). To address the short-term effects of MXC on fertility, the differential effects of MXC dosage and timing of administration (relative to implantation) on Several gestational parameters were investigated. When MXC was administered during early pregnancy (Days 1-8), a dose-dependent decline in implantations and uterine weight was seen with no effect on ovarian weight or corpora lutea; MXC reduced serum progesterone at all doses. Preimplantation administration of MXC (Days 1-3 of pregnancy) produced a decline in implantations and uterine weight, while postimplantation dosing (Days 4-8 of pregnancy) increased resorptions to l00%, decreased uterine weight, and reduced serum progesterone without affecting the number ofimplantations, ovarian weight, or number of corpora lutea. The DCR of pseudopregnancy was inhibited by 500 mg/k/day MXC when administered either pre- or postimplantation, but 200 mg/kg/day was without effect in either regimen. When hormonally primed, long-term ovariectomized rats were exposecl to doses of 500 mg/ltg/day, MXC blocked the induced DCR seen in controls. The data show that short-term MXC dosing during early pregnancy produces a dose-related infertility. The blockade of pregnancy by the preimplantation administration of MXC may be mediated by a direct effect on preimplantation uterine development. The fetal resorption seen following postimplantation dosing is considered a manifestation of both reduced serum progesterone and the direct disruption of normal decidual development by MXC