Testis

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

Abstract
Testicular apoptosis is involved in the regulation of germ cells number, 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 gonadotrophins 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-MIS 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 gonadotrophin deficiency as well as the first report of Sertoli cell apoptosis in response to gonadotrophin deficiency in the mouse.

Key words: Testis • Apoptosis • Follicle-stimulating hormone • Gonadotropin-releasing hormone • Sertoli cells

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