Effects of progesterone antagonist ZK 98.299 on early pregnancy and foetal outcome in bonnet monkeys.
The antiprogestin ZK 98.299 (onapristone) was injected subcutaneously (25 mg/day) for 4 consecutive days during early pregnancy to 8 bonnet monkeys. Retrospective analysis of the data showed that the treatment was initiated between 20 to 30 days after the mid-cycle peak in estradiol levels. In 7 animals, vaginal bleeding was induced within 3.6 +/- 2.7 days (mean +/- S.D.) after the initiation of treatment. However, pregnancy was terminated completely only in 5 animals. In these 5 animals, menstruation was induced 1 to 4 days after the initiation of treatment. Serum progesterone levels also decreased; however, a significant decrease (p less than 0.02) in mean levels was not observed until 5 days after the initiation of treatment. In the other 3 animals, in spite of some drop in serum progesterone levels after the treatment and slight vaginal bleeding in 2 animals, the pregnancy continued. Two animals delivered stillborn foetuses at term. The foetuses weighed 92 and 105 g, which is markedly lower than the normal foetal weight (345 +/- 48 g, n = 6) at birth. The gross appearance of the foetuses was suggestive of recent intrauterine foetal death. In the third animal hysterotomy was performed on day 65; foetus weighed 5 g. Haematoma and blood clots were seen in the placental tissue. This limited data on 8 animals demonstrates that ZK 98.299, at the dose regimen employed, completely terminates early pregnancy in 62% of animals. In the cases in which treatment failed, the pregnancy did not continue unaffected. The endocrine function of the placenta was affected and the foetal growth was retarded.(ABSTRACT TRUNCATED AT 250 WORDS)
Puri
C P
CP
Institute for Research in Reproduction (ICMR) Parel, Bombay, India.
Patil
R K
RK
Elger
W A
WA
Pongubala
J M
JM
D000028:Abortion, Induced; D000818:Animals; D005260:Female; D006067:Gonanes / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008255:Macaca radiata; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D011256:Pregnancy Outcome; D011374:Progesterone / Q000037:antagonists & inhibitors*; D013997:Time Factors
D006067:Gonanes; D011374:Progesterone; C053238:onapristone