{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T11:06:18Z","timestamp":1745233578788},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,5,31]],"date-time":"2005-05-31T00:00:00Z","timestamp":1117497600000},"content-version":"vor","delay-in-days":8096,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1983,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thirty timed\u2010mated pregnant rhesus monkeys received Norlestrin (Norethindrone acetate, 2.5 mg, and ethinyl estradiol, 0.05 mg pertablet, Parke\u2010Davis) orally at four different dose levels. The dose levels were 5, 10, 25 and 50 mg\/day\/monkey and the doses were administered during early (days 21\u201335), late (days 33\u201346), and throughout (days 21\u201346) organogenesis, except for the 50\u2010mg\u2010dose\u2010group animals, which were treated only during early organogenesis (days 21\u201335). All except the animals in the 50\u2010mg\u2010dose group were allowed to go to term (165 days gestation). Pregnancy for the animals in the 50\u2010mg\u2010dose group was terminated by eesarean section on day 50 of gestation and the fetuses were fixed, serially sectioned, and examined histologically. No teratogenicity was observed. However, the prenatal mortality rate (38.5%) was higher for the Norlestrin\u2010treated animals than in the control colony (21%). Eight animals aborted between days 40 and 78 of gestation and two other cases resulted in stillbirths at 139 and 165 days of gestation. There was a higher incidence of abortion (44.4%) in the 25\u2010mg\u2010dose group. Norlestrin treatment during early organogenesis also resulted in a higher abortion rate (37.5%) compared to treatment during late organogenesis (22.2% abortions). No morphological abnormalities were found in infants observed at birth or in juvenile monkeys which died of natural causes or in those that were sacrificed over a period of two years. No histopathology was observed in the 50\u2010day\u2010old fetuses examined by serial section. Examination of endogenous maternal serum estrogen and progesterone levels in Norlestrin\u2010treated monkeys (25 mg\/day, days 21\u201335) suggested that placental steroidogenesis was not affected; however, the lower levels of estrogen in maternal serum suggested that the ovarian steroidogenesis was affected. Although the precise pathogenesis of this selective embryolethality is not known, several observations in this study suggest a direct generalized embryotoxic effect. Thus, this study for the first time has demonstrated that, while Norlestrin may be embryolethal at 100 times the human contraceptive dose equivalent (25 mg\/day) in the rhesus monkey, nevertheless it does not affect the offspring which survive the exposure.<\/jats:p>","DOI":"10.1002\/tera.1420270209","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T14:45:00Z","timestamp":1118501100000},"page":"215-222","source":"Crossref","is-referenced-by-count":15,"title":["Embryotoxicity of Norlestrin, a combined synthetic oral contraceptive, in rhesus macaques (<i>Macaca mulatta<\/i>)"],"prefix":"10.1002","volume":"27","author":[{"given":"S.","family":"Prahalada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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