Role of Androgens in Fetal Testis Development and Dysgenesis

• DOI: 10.1210/en.2006-1622
• Publication Date: 2007-02-09T02:04:44Z
• Authors: Hayley M. Scott; Gary R. Hutchison; I. Kim Mahood; Nina Hallmark; Michelle Welsh; Karel De Gendt; Guido Verhoeven; Peter O’Shaughnessy; Richard M. Sharpe
• Keywords: Flutamide; Anogenital distance; Testicle

This study sought to establish whether reduced androgen levels/action in the fetal rat testis induced by di(n-butyl) phthalate (DBP) contributes dysgenetic features, namely Sertoli cell number, occurrence of multinucleated gonocytes (MNG), and Leydig aggregation. Pregnant rats were administered treatments or cotreatments designed manipulate testosterone levels [DBP, propionate (TP)] action [flutamide, 7,12-dimethyl-benz[a]anthracene (DMBA)]. The aforementioned end points analyzed related intratesticular (ITT) peripheral (anogenital distance). Dysgenetic features also evaluated mice with inactivation receptor (testicular feminized ARKO mice). Exposure DBP alone, combined flutamide, DMBA, TP, resulted number ITT levels, as did exposure TP alone; coadministration + caused most severe reduction both parameters. A positive correlation between was found (r = 0.791; P 0.019). Similarly, a cotreatment, significantly increased MNG aggregation, these negatively correlated levels. flutamide DMBA alone had no significant effect on points. These findings suggest that decreases numbers might be involved aggregation MNG. However, three points, only affected ARKO/testicular absent action. Therefore, induction result from DBP-induced effects other than suppression