This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Scott, H. M. Articles by Sharpe, R. M. Search for Related Content PubMed PubMed Citation Articles by Scott, H. M. Articles by Sharpe, R. M.

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

Medical Research Council Human Reproductive Sciences Unit, Centres for Reproductive Biology (H.M.S., G.R.H., M.S.J., C.M., R.M.S.) and Cardiovascular Science (A.J.D.), Queen’s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom

Address all correspondence and requests for reprints to: Richard M. Sharpe, Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom. E-mail: r.sharpe{at}hrsu.mrc.ac.uk.

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.

This article has been cited by other articles:

				C. McKinnell, R. T. Mitchell, M. Walker, K. Morris, C. J.H. Kelnar, W H. Wallace, and R. M. Sharpe Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset Hum. Reprod., June 2, 2009; (2009) dep200v1. [Abstract] [Full Text] [PDF]

				M. Welsh, R. M. Sharpe, M. Walker, L. B. Smith, and P. T. K. Saunders New Insights into the Role of Androgens in Wolffian Duct Stabilization in Male and Female Rodents Endocrinology, May 1, 2009; 150(5): 2472 - 2480. [Abstract] [Full Text] [PDF]

				L. J. S. Brokken, A. Adamsson, J. Paranko, and J. Toppari Antiandrogen Exposure in Utero Disrupts Expression of Desert Hedgehog and Insulin-Like Factor 3 in the Developing Fetal Rat Testis Endocrinology, January 1, 2009; 150(1): 445 - 451. [Abstract] [Full Text] [PDF]