INSPIRING FUTURES

Role of androgens in fetal testis development and dysgenesis.

Scott, Hayley M, Hutchison, Gary R, Mahood, I Kim, Hallmark, Nina, Welsh, Michelle, De Gendt, Karel, Verhoeven, Guido, Shaugnessy, Peter and Sharpe, Richard M (2007) Role of androgens in fetal testis development and dysgenesis. Endocrinology, 148 (5). pp. 2027-2036. ISSN 0013-7227

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Abstract/Description

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



Item Type: Article
Print ISSN: 0013-7227
Uncontrolled Keywords: Fetal development; Testicular growth; Androgen level; Intra-testicular testosterone; Dysgenetic effects; Sertoli cells; Multinucleated gonocytes; Leydig cells; Empirical measures;
University Divisions/Research Centres: Faculty of Health, Life & Social Sciences > School of Life Sciences
Dewey Decimal Subjects: 500 Science > 540 Chemistry > 547 Organic chemistry
600 Technology > 610 Medicine & health > 616 Diseases
Library of Congress Subjects: R Medicine > RC Internal medicine
Q Science > QP Physiology
Item ID: 1665
Depositing User: RAE Import
Date Deposited: 27 Jun 2008 15:06
Last Modified: 18 Feb 2013 14:52
URI: http://researchrepository.napier.ac.uk/id/eprint/1665

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