Antifertility effect of methoxychlor in female rats: dose- and time-dependent blockade of pregnancy.
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 100%, decreased uterine weight, and reduced serum progesterone without affecting the number of implantations, ovarian weight, or number of corpora lutea. The DCR of pseudopregnancy was inhibited by 500 mg/kg/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 exposed to doses of 500 mg/kg/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 bloickade 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.
Cummings
A M
AM
Reproductive Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Gray
L E
LE
D000818:Animals; D003656:Decidua / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D008731:Methoxychlor / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011255:Pregnancy Maintenance / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D011555:Pseudopregnancy; D051381:Rats; D013997:Time Factors; D014599:Uterus / Q000187:drug effects
D011374:Progesterone; D008731:Methoxychlor