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VALIDATION OF PROTOCOLS FOR ASSESSING EARLY PREGNANCY FAILURE IN THE RAT: CLOMIPHENE CITRATE
Citation:
Cummings, A., S. Perreault, AND S. Harris. VALIDATION OF PROTOCOLS FOR ASSESSING EARLY PREGNANCY FAILURE IN THE RAT: CLOMIPHENE CITRATE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/118 (NTIS PB91207118).
Description:
Following the assembly of a battery of protocols for the assessment of maternally-mediated toxicity during early pregnancy, the validation of this battery for its utility in detecting and defining mechanisms of early pregnancy failure is ongoing. his report describes the use of clomiphene citrate (CC), an estrogen agonist/antagonist, in these protocols as part of the validation process. he several protocols involve dosing rats with CC during and evaluation of multiple endpoints following (a) the first 8 days of pregnancy; (b) early pseudopregnancy, accompanied by decidual induction; and (c) the pre- and post implantation intervals of early pregnancy. n addition, the effect of CC on embryo transport rate was assessed. ight days of dosing with CC produced a dose-dependent reduction in the number of implantation sites seen on Day 9, concomitant with alterations in maternal hormonal parameters. o effect on the Decidual Cell Response (DCR) was found, indicating that the mechanism of fertility reduction was not mediated ia compromised uterine function. he preimplantation period was highly vulnerable to the toxic effects of CC while no postimplantation resorptions were seen. hen embryo transport rate was measured, a statistically significant embryo transport rate was detected that was insufficient to account for the observed preimplantation loss. he data suggest a direct effect of CC on the embryo or on its ability to implant as the primary mechanism mediating CC-induced early pregnancy failure. he battery of protocols was thus successful in identifying CC as a reproductive toxicant and in elucidating the causes of the observed early pregnancy failure.