Decreased angiotensin receptor 1 expression in\u2009±\u2009AT1 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\u2009±\u2009AT1KO 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\u2009±\u2009AT1KO mice was detected by quantitative real-time polymerase chain reaction (QRT-PCR). Serum GnRH level was determined by ELISA. Results Compared to control,\u2009±\u2009AT1KO 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\u2009±\u2009AT1KO mice was detected. Treatment with angiotensin receptor blocker (ARB) did not have significant effects on HPG hormones.\u2009±\u2009AT1KO 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.