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This Article Full Text Full Text (PDF) [Supplemental Data] All Versions of this Article: 78/1/77    most recent biolreprod.107.060970v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chausiaux, O. E Articles by Affara, N. A Search for Related Content PubMed PubMed Citation Articles by Chausiaux, O. E Articles by Affara, N. A Agricola Articles by Chausiaux, O. E Articles by Affara, N. A

Hypogonadal Mouse, a Model to Study the Effects of the Endogenous Lack of Gonadotropins on Apoptosis¹

Department of Human Anatomy and Genetics,⁵ University of Oxford, Oxford OX1 3QX, United Kingdom and Mammary Apoptosis and Development Group,⁴ Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom Human Molecular Genetics Group,³

ABSTRACT

Testicular apoptosis is involved in the regulation of germ cell numbers, allowing optimal sperm production. Apoptosis has been described to occur in response to the absence of hormonal stimulation of the testis. Here we investigate the effect of the physiological lack of gonadotropins from birth using the hypogonadal (homozygous for the mutant allele Gnrh1^hpg) mouse as a model. We pursued a concerted strategy using microarray analysis and RT-PCR to assess transcript levels, TUNEL to quantify the incidence of apoptosis, and Western blotting to assess the respective contribution of the extrinsic and intrinsic apoptotic pathways. Our results indicate a large increase in apoptosis of both somatic and germ cell compartments in the hpg testis, affecting Sertoli cells as well as germ cells of all ages. We confirmed our observations of Sertoli cell apoptosis using anti-Mullerian inhibiting substance staining and staining for cleaved fodrin alpha. In the somatic compartment, apoptosis is primarily regulated via the membrane receptor (extrinsic) apoptotic pathway, while in the germ cell compartment, regulation occurs via both the mitochondrial (intrinsic) and membrane receptor (extrinsic) apoptotic pathways, the latter potentially in a stage-specific manner. This study is the first report of spermatogonial apoptosis in response to gonadotropin deficiency as well as the first report of Sertoli cell apoptosis in response to gonadotropin deficiency in the mouse.

apoptosis, follicle-stimulating hormone, gonadotropin-releasing hormone, Hpg,, leutenizing hormone, sertoli cells, testis

¹Supported by BBSRC 8/EGH16106 (to O.E.C., P.J.I.E., and N.A.A.).

Correspondence: ²Nabeel Affara, Human Molecular Genetics Group, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, U.K. FAX: +44 1223 333700; e-mail: na{at}mole.bio.cam.ac.uk

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