Fertility and spermatogenesis are altered in α1b-adrenergic receptor knockout male mice

Abstract

To examine whether norepinephrine, through activation of a1b-adrenergic receptor, regulates male fertility and testicular functions, we used a1b-adrenergic receptor knockout (a1b-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 (K55 and K81% in hypofertile and infertile males respectively versus wild-type males). Consequently, circulating levels of LH were significantly elevated in a1b-AR-KO infertile mice. When incubated in vitro, the whole testes from infertile KO mice released significantly lower levels of testosterone (K40%). 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 a-and bB-subunits in Sertoli cells of infertile a1b-AR-KO mice. This was correlated with a higher intratesticular content of inhibin B (C220% above wild-type mice). Using specific primers, mRNA encoding a1b-AR was localized in early spermatocytes of wild-type testes. Our results indicate, for the first time, that a1b-AR signaling plays a critical role in the control of male fertility, spermatogenesis, and steroidogenic capacity of Leydig cells. It is thus hypothesized that the absence of a1b-AR alters either directly germ cells or indirectly Sertoli cell/Leydig cell communications in infertile a1b-AR-KO mice.

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: Background to spermatogenesis, spermatogonia, and spermatocytes

“…Absence of ADRA1B in mice may alter spermatocytes directly by interfering with the normal action of catecholamines on these cells and thus affect the normal progression of spermatogenesis. Alternatively, germ cell ADRA1B signaling may produce paracrine factors that regulate Leydig cell homeostasis and hence testosterone production (Mhaouty-Kodja et al, 2007). Tex19.1 [ID: T1-155], a nuclear protein, is highly expressed in mitotic spermatogonia and then diminishes as these cells differentiate and progress through meiosis (Kuntz et al, 2008).…”

Sex-associated DNA markers from turbot

“…Recent data obtained from knockout mice indicate that alpha 1b adrenergic receptor signalling is essential for male fertility in mammals, as in the absence of the functional product both spermatogenesis and the steroidogenic capacity of the Leydig cells are compromised (Mhaouty-Kodja et al 2007). Moreover, data from the study of Itoh & Ishizuka (2005) also indicate that alpha1 adrenergic receptors seem to play an important role in ovarian function as well.…”

Could α1-adrenoceptors and androgen receptors be modified by sexual maturation and testosterone in the rat testicular capsule?

“…In addition, Mhaouty-Kodja et al (2007) showed that in both phenotypes circulating testosterone plasma levels were highly reduced in hypofertile and infertile and that the in vitro released of testosterone of their testes was also significantly lower, indicating that α 1 -adrenoceptor signaling may play a critical role in the control of male fertility, spermatogenesis, and steroidogenic capacity. The relevance and role of the α 1 -adrenoceptors in the testicular capsule to male fertility in these experimental models still requires investigation.…”

“…Its surgical removal can significantly reduce fertility of rats Lung, 2000, 2001), while contractile dysfunctions have been implicated in male infertility (Mulryan et al 2000;Mhaouty-Kodja et al 2007;Sanbe et al 2007).…”

“…The use of mice with targeted disruption of each of the three α 1 -adrenoceptor subtypes (either single or tripleknockout mice) also suggest that α 1A -subtype are required for normal motor activity of the vas deferens and sperm ejaculation (Mulryan et al 2000;Mhaouty-Kodja et al 2007;Sanbe et al 2007). Mhaouty-Kodja et al (2007) also observed that most of the α 1 -adrenoceptor adult knockout homozygous males (73%) was hypofertile, with relatively preserved spermatogenesis while remaining males (27%) exhibited a complete infertility with a drastic reduction in testicular weight and presenting spermatogenesis defect.…”