Androgen receptor roles in spermatogenesis and infertility

Abstract

Androgens such as testosterone are steroid hormones essential for normal male reproductive development and function. Mutations of androgen receptors (AR) are often found in patients with disorders of male reproductive development, and milder mutations may be responsible for some cases of male infertility. Androgens exert their action through AR and its signalling in the testis is essential for spermatogenesis. AR is not expressed in the developing germ cell lineage so is thought to exert its effects through testicular Sertoli and peri-tubular myoid (PTM) cells. AR signalling in spermatogenesis has been investigated in rodent models where testosterone levels are chemically supressed or models with transgenic disruption of AR. These models have pinpointed the steps of spermatogenesis that require AR signalling, specifically maintenance of spermatogonial numbers, blood-testis barrier integrity, completion of meiosis, adhesion of spermatids and spermiation, together these studies detail the essential nature of androgens in the promotion of male fertility.

The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

“…Although the current study shows that LH is more likely to be raised at last presentation, in a substantial subset of cases, FSH was also raised, highlighting the possibility of progressive primary gonadal failure in boys with PAIS. Although in some cases the testicular failure may have been related to maldescent of the testis or the subsequent orchiopexy, most of the cases with high gonadotropins did not have undescended testes, and it is possible that this biochemical picture may reflect the role of androgens in testes development and maintenance (26, 27). This is in line with the histological observation that testes in men with PAIS are prone to fibrosis and loss of testicular architecture (our unpublished observation).…”

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

“…Despite this potential, only few X-linked genes have been studied with respect to human male fertility. Mutations in the X-linked androgen receptor (AR) gene have been shown to be associated with disorders in male sexual differentiation and development (9). More recently, mutations in the X-linked gene, TEX11, have been identified as a cause of meiotic arrest and azoospermia (10,11).…”

miR-762 promotes porcine immature Sertoli cell growth via the ring finger protein 4 (RNF4) gene

“…AR is a nuclear receptor well known for its role in spermatogenesis as AR is required for complete meiosis, adhesion of spermatids, spermiation and blood-testis barrier formation1834. The overexpression of AR in immature Sertoli cells caused the cells to become premature and decreased the final mature Sertoli cell number, resulting in a reduced final germ cell number35.…”