Studies on the antifertility mechanisms of low doses of chlormadinone acetate using egg transfer in the rabbit.

Abstract

Fertilization, transport, development, and transfer of eggs was studied in rabbits treated with chlormadinone acetate (CA). Mature female rabbits were treated orally for three consecutive days with either 0.09 mg/kg/day of CA in an aqueous suspending medium or with the vehicle alone. On the last day of dosing (≡ Day 0 of pregnancy) all animals were artificially inseminated (AI) and were induced to ovulate with HCG. Recipients for egg transfer were made pseudopregnant by inducing ovulation but omitting AI. Egg recoveries on Days 2, 4, and 6 of pregnancy showed that CA interfered with fertilization, accelerated the rate of egg transport by Day 2, and interfered with blastocyst expansion by Day 4. When Day 2 eggs were flushed from the oviducts of treated donor rabbits and transferred into the oviducts of untreated recipient rabbits on Day 2 of pseudopregnancy normal implantation occurred. Day 2 transfers from untreated donors to treated recipients produced a marked reduction in the number of implantations. When Day 6 blastocysts were recovered from the uteri of treated donors and transferred into the uteri of untreated recipients on Day 6 of pseudopregnancy no viable fetuses developed. Day 6 transfers from untreated donors to treated recipients resulted in normal fetal development. The results indicate a complex antifertility effect of CA in the rabbit. A dose of 0.09 mg/kg, administered on three consecutive days before ovulation interferes with fertilization, causes acceleration of egg transport and produces ovicidal effects between Days 2 and 6 of pregnancy.