Teratological evaluation of a novel antiabortifacient, dibenzyloxyindanpropionic acid--I. Dysmorphological and histopathological studies.

Dibenzyloxyindanpropionic acid (DIPA) is an anti-abortifacient prostaglandin F2 alpha(PGF2 alpha) antagonist. Significant protection against PGF2 alpha-induced abortion in Charles River CD-1 mice is afforded by 50 mg/kg DIPA, administered i.m. twice daily from day-15 of gestation; two days prior to PGF2 alpha challenge. In the present teratological evaluation, CD-1 mice were treated either daily throughout gestation with 50 mg/kg DIPA i.m., or only on day-15 of gestation with two doses each of 50 or 200 mg/kg DIPA i.m. Controls received saline injections. Some dams were delivered by cesarian section on day-19 of gestation, while others were allowed to deliver spontaneously at term. Parameters monitored in the offspring were litter sizes, body weights, sex ratios, viability of progeny, external malformations, cleft palate, skeletal anomalies, patency (prenatal) and closure (postnatal) of the ductus arteriosus, gross anatomy of organs, and histopathological examination of tissues. Consistent with a PGF2 alpha antagonistic mechanism of action, DIPA treatment throughout gestation prolonged pregnancy to the upper normal limit. Prenatal administration of DIPA increased the pseudopregnancy rate, but none of the treatment schedules produced any recognizable teratogenic effects.