Fertility and spermatogenesis are altered in {alpha}1b-adrenergic receptor knockout male mice.
To examine whether norepinephrine, through activation of alpha1b-adrenergic receptor, regulates male fertility and testicular functions, we used alpha1b-adrenergic receptor knockout (alpha1b-AR-KO) mice. In the adult stage (3-8 months), 73% of the homozygous males were hypofertile with relatively preserved spermatogenesis. Of the remaining males, 27% exhibited a complete infertility with a drastic reduction in testicular weight and spermatogenesis defect with germ cells entering a cell death pathway at meiotic stage. In both phenotypes, circulating levels of testosterone were highly reduced (-55 and -81% in hypofertile and infertile males respectively versus wild-type males). Consequently, circulating levels of LH were significantly elevated in alpha1b-AR-KO infertile mice. When incubated in vitro, the whole testes from infertile KO mice released significantly lower levels of testosterone (-40%). This, together with the fact that the mean absolute volume of Leydig cells per testis was not changed, suggests a compromised steroidogenic capacity of Leydig cells in infertile animals. In addition, RNA in situ hybridization study indicated an apparent higher expression of inhibin alpha- and betaB-subunits in Sertoli cells of infertile alpha1b-AR-KO mice. This was correlated with a higher intra-testicular content of inhibin B (+220% above wild-type mice). Using specific primers, mRNA encoding alpha1b-AR was localized in early spermatocytes of wild-type testes. Our results indicate, for the first time, that alpha 1b-AR signaling plays a critical role in the control of male fertility, spermatogenesis, and steroidogenic capacityof Leydig cells. It is thus hypothesized that the absence of alpha1b-AR alters either directly germ cells or indirectly Sertoli cell/Leydig cell communications in infertile alpha1b-AR-KO mice.
Mhaouty-Kodja
Sakina
S
CNRS UMR 7079/Université Pierre et Marie Curie, Neuroendocrinologie de la Reproduction, 4 Place Jussieu 75230 Paris CEDEX 05, France. sakina.mhaouty-kodja@college-de-france.fr
Lozach
Anne
A
Habert
René
R
Tanneux
Magali
M
Guigon
Céline
C
Brailly-Tabard
Sylvie
S
Maltier
Jean-Paul
JP
Legrand-Maltier
Chantal
C
D000818:Animals; D005298:Fertility / Q000502:physiology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006720:Homozygote; D007248:Infertility, Male / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D007265:Inhibins / Q000378:metabolism; D007985:Leydig Cells / Q000378:metabolism / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000502:physiology; D009929:Organ Size; D012313:RNA / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012708:Sertoli Cells / Q000378:metabolism; D013090:Spermatocytes / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology*; D013256:Steroids / Q000096:biosynthesis; D013737:Testis / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014018:Tissue Distribution
C547717:Adra1b protein, mouse; D018340:Receptors, Adrenergic, alpha-1; D013256:Steroids; D013739:Testosterone; D007265:Inhibins; D012313:RNA; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D009638:Norepinephrine