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Relationship between Androgen Action in the “Male Programming Window,” Fetal Sertoli Cell Number, and Adult Testis Size in the Rat

Scott, Hayley M; Hutchison, Gary R; Jobling, Matthew S; McKinnell, Chris; Drake, Amanda J; Sharpe, Richard M

Authors

Hayley M Scott

Matthew S Jobling

Chris McKinnell

Amanda J Drake

Richard M Sharpe



Abstract

Fetal androgen action is an important determinant of Sertoli cell (SC) number at birth. Androgens “program” reproductive tract development in rats between embryonic d (e) 15.5 and e17.5 (“male programming window”), and this is reflected for life by anogenital distance (AGD). We investigated if androgen regulation of SC number/proliferation was also programmed by androgens in this window. Pregnant rats were treated in various fetal time windows with vehicle (control) or 500 mg/kg·d di(n-butyl) phthalate (DBP), which suppresses fetal intratesticular testosterone (ITT). ITT and SC number/proliferation index were determined at e17.5 or e21.5; AGD was also determined at e21.5. In controls, SC number increased 11-fold and ITT by 10-fold from e17.5–e21.5. In animals exposed daily to DBP from e13.5, SC number was reduced by approximately 50% at e21.5, but increased 6-fold, as did ITT, from e17.5–e21.5; DBP had no effect on ITT at e15.5, reduced ITT by 50% at e17.5, and by more than 75% at e19.5–21.5. DBP exposure just in the male programming window did not alter SC number at e17.5 or 21.5 but reduced AGD. DBP treatment beyond e19.5 caused major reductions in SC number/proliferation index and ITT at e21.5. Only DBP treatments that included the male programming window led to reduced AGD at e21.5, but SC number was clearly not programmed in this window. Nevertheless, testis weight correlated highly (P < 0.001) with AGD at e21.5, and postnatal d 25 and 90 in animals exposed in utero to vehicle or DBP (e13.5–e21.5). Thus, AGD may predict adult testis size but probably not through a direct relationship with SC number.

Citation

Scott, H. M., Hutchison, G. R., Jobling, M. S., McKinnell, C., Drake, A. J., & Sharpe, R. M. (2008). Relationship between Androgen Action in the “Male Programming Window,” Fetal Sertoli Cell Number, and Adult Testis Size in the Rat. Endocrinology, 149, 5280-5287. https://doi.org/10.1210/en.2008-0413

Journal Article Type Article
Publication Date 2008
Deposit Date Mar 27, 2014
Print ISSN 0013-7227
Electronic ISSN 1945-7170
Publisher Endocrine Society
Peer Reviewed Peer Reviewed
Volume 149
Pages 5280-5287
DOI https://doi.org/10.1210/en.2008-0413
Keywords Fetal androgen action; Sertoli cell (SC); anogenital distance (AGD); male programming window;
Public URL http://researchrepository.napier.ac.uk/id/eprint/6668
Publisher URL http://dx.doi.org/10.1210/en.2008-0413