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.