The male genital tract and the nipples of male and female offspring of rats given the non-steroidal antiandrogens DIMP and Sch 13521, during pregnancy.
Male and female offspring of rats given antiandrogens, the steroidal BOMT or the non steroids DIMP or Sch 13521, daily during the last third of pregnancy were studied. Detailed examinations were made of the genital tract of male, and of the nipples of male and female offspring. A) Male offspring. 1) Genital tract of newborn and 31-91 day old males : Modifications of the development of accessory sexual tissues were found in all treatment groups. As indicated by the severity of deviations from normal (morphology and weight of sex accessories), the antiandrogenic effect of the preparations, in the doses given to the mother rats, increased from BOMT (50 or 75 mg/day) via Sch 13521 (30 mg/day) and DIMP (50 or 60 mg/day) to Sch 13521 (60 mg/day). 2) Nipples of 10-60 day old males : Whole mount preparations were made unilaterally of the row of 6 mammary glands with nipples. The number of intact and abnormal nipples, respectively, was recorded. The relation between intact and abnormal nipples served as indicator of the efficiency of the antiandrogenic substances studied. The result showed that the antiandrogenic effect increased from BOMT to Sch 13521, 60 mg, in the same order as that arrived at from studies of the genital tract. The combined results obtained from the male offspring indicated that the tissues of the genital region, the growth and differentiation of which was most readily impaired by antiandrogens, were the same as those known from other work to be stimulated most easily in female rat fetuses by testosterone. B) Female offspring. Nipples of 31-60 day old females were judged from whole mount preparations and recorded as in the males. The nipples of adult virginal females were examined macroscopically. The same procedure was applied to lactating females, but the results were controlled in consecutive lactational periods and at autopsy. The 3 groups of females showed uniformly that 1) offspring of rats given BOMT during pregnancy had many (about 50 per cent) malformed nipples and 2) the treatment of mother rats with DIMP or Sch 13521 did not influence the development of nipples in female offspring. The result was assumed to be due to an androgenic effect of the steroidal antiandrogen, BOMT, on the nipple anlage.
D000014:Abnormalities, Drug-Induced; D000726:Androgen Antagonists; D000813:Anilides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001940:Breast / Q000002:abnormalities*; D004543:Ejaculatory Ducts / Q000187:drug effects; D005260:Female; D005485:Flutamide / Q000633:toxicity*; D005837:Genitalia, Male / Q000002:abnormalities* / Q000187:drug effects; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects; D009024:Morphogenesis / Q000187:drug effects; D009558:Nipples / Q000002:abnormalities* / Q000187:drug effects; D010080:Oxazoles / Q000633:toxicity*; D010797:Phthalimides / Q000633:toxicity*; D011247:Pregnancy; D011467:Prostate / Q000187:drug effects; D051381:Rats; D013739:Testosterone / Q000502:physiology; D014621:Vagina / Q000002:abnormalities
D000726:Androgen Antagonists; D000813:Anilides; D010080:Oxazoles; D010797:Phthalimides; D013739:Testosterone; D005485:Flutamide