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Sertoli Cell Development and Function in an Animal Model of Testicular Dysgenesis Syndrome1

Hutchison, Gary R.; Scott, Hayley M.; Walker, Marion; McKinnell, Chris; Ferrara, Diana; Mahood, I. Kim; Sharpe, Richard M.

Authors

Hayley M. Scott

Marion Walker

Chris McKinnell

Diana Ferrara

I. Kim Mahood

Richard M. Sharpe



Abstract

Pregnancy exposure to di(n-butyl) phthalate (DBP) in rats induces a testicular dysgenesislike syndrome (TDS) in male offspring. Earlier studies suggested altered Sertoli cell development/maturation may result, especially in testes that become cryptorchid. This study quantitatively assessed Sertoli cell numerical and functional development in DBP-exposed rats and compared (unilaterally) cryptorchid and scrotal testes. Pregnant rats were gavaged with 500 mg/kg/day DBP or cornoil from embryonic (E) Days 13.5 to 21.5. Male offspring were sampled on E21.5 or Postnatal Day 6, 10, 15, 25, or 90. Sertoli cell number in DBP-exposed males was reduced by ;50% at E21.5 but recovered to normal by Days 25–90, accompanied by
significant changes in plasma inhibin B and testosterone levels. Sertoli cell maturational development in DBP-exposed males, assessed using five protein markers (anti-mu¨llerian hormone, cytokeratin, androgen receptor, CDKN1B, and Nestin), was largely normal, with some evidence of delayed maturation. However, in adulthood, Sertoli cells (SC) in areas lacking germ cells (Sertoli cell-only [SCO] tubules) often exhibited immature features, especially in cryptorchid testes. Sertoli cells in DBPexposed animals supported fewer germ cells during puberty, but this normalized in scrotal testes by adulthood. Scrotal and especially cryptorchid testes from DBP-exposed animals exhibited abnormalities (SCO tubules, focal dysgenetic areas) at all postnatal ages. Cryptorchid testes from DBP-exposed animals exhibited more Sertoli cell abnormalities at Day 25 compared with scrotal testes, perhaps indicating more severe underlying Sertoli cell malfunction in these testes. Our findings support the concept of altered Sertoli cell development in TDS, especially in cryptorchid testes, but show that maturational defects in Sertoli cells in adulthood most commonly reflect secondary dedifferentiation in absence of germ cells.

Citation

Hutchison, G. R., Scott, H. M., Walker, M., McKinnell, C., Ferrara, D., Mahood, I. K., & Sharpe, R. M. (2008). Sertoli Cell Development and Function in an Animal Model of Testicular Dysgenesis Syndrome1. Biology of Reproduction, 78(2), 352-360. https://doi.org/10.1095/biolreprod.107.064006

Journal Article Type Article
Acceptance Date Sep 28, 2007
Online Publication Date Oct 10, 2007
Publication Date Feb 1, 2008
Deposit Date May 1, 2019
Journal Biology of Reproduction
Print ISSN 0006-3363
Electronic ISSN 1529-7268
Publisher Society for the Study of Reproduction
Peer Reviewed Peer Reviewed
Volume 78
Issue 2
Pages 352-360
DOI https://doi.org/10.1095/biolreprod.107.064006
Keywords di(n-butyl) phthalate (DBP), rat, Sertoli cell number, testicular dysgenesis syndrome (TDS), testis development
Public URL http://researchrepository.napier.ac.uk/Output/1749702