Decreased angiotensin receptor 1 expression in ± AT1 Knockout mice testis results in male infertility and GnRH reduction

Abstract

Background This study aimed to detect the effect of angiotensin receptor 1 (AT1) knock out (KO) on spermatogenesis and hypothalamic-pituitary–gonadal (HPG) axis hormone expression. Methods Normal C57BL/6 male mice were used as control group or treated with angiotensin receptor blocker, in addition heterozygous ± AT1KO mice were generated. After caged at a ratio of 2 to 1 with females, pregnancy rates of female mice were determined by detection of vaginal plugs. Deformity rate of spermatozoa was evaluated by eosin staining and morphology evaluation. The AT1 mRNA expression in the testes of male ± AT1KO mice was detected by quantitative real-time polymerase chain reaction (QRT-PCR). Serum GnRH level was determined by ELISA. Results Compared to control, ± AT1KO mice showed reduced expression of AT1 in testes, pituitary and hypothalamus. In addition, decreased level of GnRH, but not follicle stimulating hormone (FSH) or luteinizing hormone (LH), in ± AT1KO mice was detected. Treatment with angiotensin receptor blocker (ARB) did not have significant effects on HPG hormones. ± AT1KO mice exhibited male infertility and significant abnormality of sperm morphology. Conclusion Reduced AT1 knockout resulted in male infertility, potentially by inducing abnormal spermatogenesis. Both testis and HPG axis signaling may be involved.

G-Protein Coupled Receptors in Human Sperm: An In Silico Approach to Identify Potential Modulatory Targets

“…Despite not being described in the MGI database, prosaposin receptor GPR37 null mice presented abnormal testis morphology, altered spermatogenesis, and decreased sperm concentration and motility [ 47 ]. Additionally, Agtr1 knock-out mice had abnormal sperm morphology and male infertility, probably due to abnormal spermatogenesis [ 48 ].…”

Losartan Attenuates Radiation-Induced Damage on Testes and Accelerates Tubular Regeneration

“…Through this axis, Ang II may promote negative regulation of testosterone production by inhibition of the adenylate cyclase activity in rat Leydig cell membranes due to the reduced gonadotropin-stimulated cAMP ( 26 , 46 ). In addition, AT1R is present in germ cells at different maturation stages, and its involvement in the regulation of spermatogenesis has been suggested ( 47 , 48 ). Considering that Ang II produced in the testes modulates steroidogenesis in Leydig cells through AT1R, blocking this pathway is likely related to the potential radioprotection mechanisms of losartan.…”

“…Interestingly, the inhibition by losartan of the Ang II/AT1R axis 60 days after irradiation did not exert any influence on the serum LH and FSH levels. In a previous study that investigated the role of AT1R on spermatogenesis and expression of hormones from the hypothalamic-pituitary-gonadal (HPG) axis in both wild C57BL/6 and ± AT1 knockout mice, it was demonstrated that losartan had no significant effect on the LH and FSH levels ( 48 ). However, 180 days after exposure to a single dose of radiation (9 Gy) on the testes, no change in FSH levels was observed until the 23rd day post-irradiation ( 49 ).…”