Validation of Protocols for Assessing Early Pregnancy Failure in the Rat: Clomiphene Citrate

摘要

Following the assembly of a battery of protocols for the assessment of maternally-mediated toxicity during early pregnancy, the validation of the battery for its utility in detecting and defining mechanisms of early pregnancy failure is ongoing. The report describes the use of clomiphene citrate (CC), an estrogen agonist/antagonist, in these protocols as part of the validation process. The several protocols involve dosing rats with CC during and evaluation of multiple endpoints following (1) the first 8 days of pregnancy; (2) early pseudopregnancy, accompanied by decidual induction; and (3) the pre- and post implantation intervals of early pregnancy. In addition, the effect of CC on embryo transport rate was assessed. The 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. The battery of protocols was thus successful in identifying CC as a reproductive toxicant and in elucidating the causes of the observed early pregnancy failure.