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

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 usi...

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Published inBiology of reproduction Vol. 78; no. 1; pp. 77 - 90
Main Authors Chausiaux, Oriane E, Abel, Margaret H, Baxter, Fiona O, Khaled, Walid T, Ellis, Peter J. I, Charlton, Harry M, Affara, Nabeel A
Format Journal Article
LanguageEnglish
Published Society for the Study of Reproduction, Inc 01.01.2008
Subjects
apoptosis
follicle-stimulating hormone
gonadotropin-releasing hormone
Hpg
leutenizing hormone
sertoli cells
testis
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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 Gnrh1hpg) 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.
AbstractList 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 Gnrh1hpg) 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.
Author Ellis, Peter J. I
Khaled, Walid T
Abel, Margaret H
Affara, Nabeel A
Charlton, Harry M
Chausiaux, Oriane E
Baxter, Fiona O
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Snippet Testicular apoptosis is involved in the regulation of germ cell numbers, allowing optimal sperm production. Apoptosis has been described to occur in response...
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bioone
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StartPage 77
SubjectTerms apoptosis
follicle-stimulating hormone
gonadotropin-releasing hormone
Hpg
leutenizing hormone
sertoli cells
testis
Title Hypogonadal Mouse, a Model to Study the Effects of the Endogenous Lack of Gonadotropins on Apoptosis1
URI http://www.bioone.org/doi/abs/10.1095/biolreprod.107.060970
Volume 78
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