ACTION D'UNE SUBSTANCE PROGESTATIVE SYNTHETIQUE 17α-ALLYL-4-OESTRENE-17β-OL SUR LA DIFFERENCIATION SEXUELLE DES FOETUS DE RAT

Abstract

ABSTRACT Allylestrenol was given to pregnant rats from day 13 to day 20 or 21 of pregnancy. Four different treatments were used: 1) drug given subcutaneously to castrated mother animals 2) drug given subcutaneously to non castrated mothers; 3) drug given by mouth to castrated mothers; and 4) drug given by mouth to non castrated mothers. At term anomalies of the genital tract of the female foetuses were observed in groups 2, 3 and 4; the highest frequency and severity was observed in group 4, and the lowest in group 2. The trans-intestinal route and the presence of the maternal ovaries favour the occurrence of anomalies (by metabolic conversion of the drug?). The males were normal. In the female foetuses the main anomalies were: complete or partial persistence of the Wolffian ducts in many foetuses; inhibition of the separation of the posterior vaginal cord from the urethra; slight anterior flexure of the uro-genital sinus and some increase in the length of the ano-genital distance; slight anomalies of the genital tubercle. In females from group 4, reared postnatally until adult, the Wolffian ducts retrogress and there is late development of the vaginal cord (and duct); but the posterior vagina and the clitoris remain abnormal. The anomalies produced by allylestrenol in females are more similar to those produced by oestrogens than to those produced by androgens (the latter are permanent and include masculinization of the uro-genital sinus). But in pregnant rats given oestrogens the male foetuses are abnormal. It is not justifiable to interpret the persistence of Wolffian ducts or vaginal inhibition at birth as signs of masculinization when they are not permanent, since similar transient anomalies can be produced by oestrogens. For these reasons, and also for testing the reproductive capacities of animals treated pre-natally with steroids, the evaluation of the effect of a new compound on the young should include postnatal rearing and study.