Teratogenic effects of cyproterone acetate and medroxyprogesterone treatment during the pre- and postimplantation period of mouse embryos. II. Cyproterone acetate and medroxyprogesterone acetate treatment before implantation in vivo and in vitro.

The study was performed to investigate direct embryotoxic effects of maternal progestin treatment during the preimplantation period. In the first experiment pregnant mice received a single subcutaneous injection of either cyproterone acetate (CA) or medroxyprogesterone acetate (MPA) on day 2 of pregnancy (5-600 mg/kg). In a second experiment four-cell embryos were exposed to CA or MPA in vitro (3 or 30 micrograms/ml medium). Our results revealed: (1) After maternal treatment the number of live embryos was reduced after the highest CA dose. Development into blastocysts was inhibited in a dose-related manner after CA but not after MPA. The number of cells in morulae, blastocysts, and of the inner cell mass (ICM) of late blastocysts was not affected. (2) When morulae and blastocysts were cultured in vitro after maternal treatment, hatching, attachment, and trophoblast outgrowth were inhibited after high doses, but development and differentiation of the ICM were inhibited even after low doses. (3) Application of 30 micrograms/ml of CA or MPA in vitro was directly embryolethal. Three micrograms/ml did not affect development into blastocysts, but ICM development and differentiation were again inhibited during subsequent culture in hormone-free medium. (4) Qualitative protein synthesis was altered in morulae and blastocysts 24 hours after maternal CA treatment. According to our results high doses of progestins are embryotoxic before implantation, low doses have delayed effects on embryonic development that are particularly evident after implantation in vitro.