Effect of FSH on testicular morphology and spermatogenesis in gonadotrophin-deficient hypogonadal mice lacking androgen receptors

O'Shaughnessy, P.J. , Monteiro, A., Verhoeven, G., De Gendt, K. and Abel, M.H. (2010) Effect of FSH on testicular morphology and spermatogenesis in gonadotrophin-deficient hypogonadal mice lacking androgen receptors. Reproduction, 139(1), pp. 177-184. (doi:10.1530/REP-09-0377)

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Abstract

Follicle stimulating hormone (FSH) and androgen act to stimulate and maintain spermatogenesis. FSH acts directly on the Sertoli cells to stimulate germ cell number and acts indirectly to increase androgen production by the Leydig cells. In order to differentiate between the direct effects of FSH on spermatogenesis and those mediated indirectly through androgen action we have crossed hypogonadal (hpg) mice which lack gonadotrophins with mice lacking androgen receptors (AR) either ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). These hpg.ARKO and hpg.SCARKO mice were treated with recombinant FSH for 7 days and testicular morphology and cell numbers assessed. In untreated hpg and hpg.SCARKO mice germ cell development was limited and did not progress beyond the pachytene stage. In hpg.ARKO mice testes were smaller with fewer Sertoli cells and germ cells compared to hpg mice. Treatment with FSH had no effect on Sertoli cell number but significantly increased germ cell numbers in all groups. In hpg mice FSH increased numbers of spermatogonia and spermatocytes and induced round spermatid formation. In hpg.SCARKO and hpg.ARKO mice, in contrast, only spermatogonial and spermatocyte numbers were increased with no formation of spermatids. Leydig cell numbers were increased by FSH in hpg and hpg.SCARKO mice but not in hpg.ARKO mice. Results show that in rodents 1) FSH acts to stimulate spermatogenesis through an increase in spermatogonial number and subsequent entry of these cells into meiosis, 2) FSH has no direct effect on the completion of meiosis and 3) FSH effects on Leydig cell number are mediated through interstitial ARs.

Item Type:Articles
Additional Information:“Disclaimer. This is not the definitive version of record of this article. This manuscript has been accepted for publication in Reproduction, but the version presented here has not yet been copy edited, formatted or proofed. Consequently, the journal accepts no responsibility for any errors or omissions it may contain. The definitive version is available at http://dx.doi.org/10.1530/REP-09-0377. © 2010 Society for Reproduction and Fertility.”
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Monteiro, Dr Ana and O'Shaughnessy, Professor Peter
Authors: O'Shaughnessy, P.J., Monteiro, A., Verhoeven, G., De Gendt, K., and Abel, M.H.
Subjects:Q Science > QP Physiology
Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Reproduction
Publisher:Society for Reproduction and Fertility
ISSN:1470-1626
ISSN (Online):1741-7899
Copyright Holders:Copyright © 2010 Society for Reproduction and Fertility
First Published:First published in Reproduction 139(1):177-184
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
413101Testicular function in mice lacking sertoli cell androgen receptors and FSH receptorsPeter O'ShaughnessyWellcome Trust (WELLCOME)078137/Z/05/ZInstitute of Biodiversity Animal Health and Comparative Medicine