Teratogenic effects of cyproterone acetate and medroxyprogesterone treatment during the pre- and postimplantation period of mouse embryos. I.
Pregnant mice were treated with a single subcutaneous injection of either cyproterone acetate (CA) or medroxyprogesterone acetate (MPA). In the first experiment the animals received 5-900 mg/kg of the hormone before implantation (day 2 of pregnancy). CA treatment on day 2 caused a dose-dependent decrease in fetal weight and a significant dose-dependent increase in the rates of cleft palate and urinary tract abnormalities. Exencephaly and heart abnormalities were also significantly more frequent, but this increase was not dose-dependent. MPA treatment on day 2 was followed by sporadic increases in dead and resorbed fetuses, a decrease in fetal weight and an increase in the rates of cleft palate, and malformed or abnormally developed fetuses. None of these effects, however, was dose-dependent. In the second experiment the mice were given one single injection (30 mg/kg) of CA or MPA on any one of days 1-12 of gestation. Treatment with CA on one day between days 1 and 12 revealed that the specific sensitivity for abnormalities of the urinary tract was on days 5 and 6, for the respiratory tract on days 8 and 9, and for cleft palate on days 10 and 11. Treatment with MPA on one day between days 1 and 12 only revealed a high rate of respiratory and urinary tract abnormalities on day 9. After treatment with MPA cleft palate was again significantly more frequent in all treated groups, however, days of peak sensitivity were not detected. The long half-life of CA (60 hours) explains the teratogenic effect of high doses of this progestin after treatment on day 2 and also the pattern of abnormal development found after treatment with a single dose of CA on one of the days between day 1 and day 12.
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced; D003272:Contraceptive Agents, Male / Q000633:toxicity; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000633:toxicity; D017373:Cyproterone Acetate; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000139:chemically induced; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000633:toxicity; D017258:Medroxyprogesterone Acetate; D051379:Mice; D011247:Pregnancy; D015619:Respiratory System Abnormalities; D012886:Skull / Q000002:abnormalities; D014551:Urinary Tract / Q000002:abnormalities
D003272:Contraceptive Agents, Male; D017373:Cyproterone Acetate; D017258:Medroxyprogesterone Acetate; D003534:Cyproterone; D008525:Medroxyprogesterone