Synergistic effect of follicle-stimulating hormone receptor and androgen receptor gene variants on semen quality

Abstract

Follicle-stimulating hormone (FSH), interacting with its receptor (FSHR), participates in the production of spermatozoa and androgens. Androgens exert their effects on male sex determination, development and sperm production by binding to androgen receptor (AR). In the present study, we sought to explore the potential synergistic effects of FSHR and AR gene variants on sperm quality. 200 oligozoospermic and 250 normozoospermic men were examined. DNA was extracted from spermatozoa, and the FSHR 307 (T/A), FSHR 680 (N/S) and AR (CAG)n polymorphisms were genotyped. Their parallel analysis revealed six combined genotypes. A gradual reduction of sperm motility, from long AR allele-Thr307Thr/Asn680Asn carriers to long AR allele-Ala307Ala/Ser680Ser carriers and from short AR allele-Thr307Thr/Asn680Asn carriers to short AR allele-Ala307Ala/Ser680Ser carriers was revealed in normozoospermic men (P < 0.001). Similar associations were observed in oligozoospermic men (P < 0.001). In our series, the synergism of the long AR alleles with the FSHRThr307/Asn680 allelic variant was associated with increased sperm motility, while the synergism of the short AR alleles with the FSHRAla307/Ser680 allelic variant was associated with decreased motility, supporting the significance of these genes in semen quality.

Genetic Association Between Androgen Receptor Gene CAG Repeat Length Polymorphism and Male Infertility

“…Eventually, 41 English and 3 Chinese reports meet all criteria of inclusion. 1,12–28,31–37,39,40,42–49,51–53,56–58,61,62,64 The characteristics of the selected studies are shown in Table 1. One report 25 included studies on 2 different ethnic groups, so we consider it as 2 separate studies.…”

“…Data of azoospermic group were provided by 19 reports. 12–24,27,28,33,37,42,45 Six reports 13,17,25,32,61,62 provided data of oligospermic group without further stratification. Some reports 12,14–16,18-21,23,24 classify oligospermic group according to sperm concentration.…”

Alterations of the FSH and LH receptor genes and evaluation of sperm ultrastructure in men with idiopathic hypergonadotropic hypogonadism

“…However, the hypothesis that the combination of heterozygous FSHR (codon 307 and 607) can be responsible for male infertility was reported by Shimoda et al [11]. Recently, the synergic effect of FSHR 307 and FSHR 680 polymorphisms and androgen receptors on semen quality was described by Lazaros et al [23]. Similarly, the polymorphisms found in our patients might, in combination with each other, predispose for infertility although they are not directly involved in the production of a non-functioning receptor.…”

Effect of sexual steroids on boar kinematic sperm subpopulations

“…Polymorphisms of the aromatase gene possibly impair aromatase activity, and are related with decreased sperm motility in humans . In a similar way, expression of distinct polymorphisms of the androgen receptor modify the impact of testosterone on sperm motility . Furthermore, there is synergism between several pairs of genes related to sperm motility: androgen receptor‐aromatase, androgen receptor‐FSH receptor, and androgen receptor‐sexual hormone binding globulin .…”

“…In a similar way, expression of distinct polymorphisms of the androgen receptor modify the impact of testosterone on sperm motility . Furthermore, there is synergism between several pairs of genes related to sperm motility: androgen receptor‐aromatase, androgen receptor‐FSH receptor, and androgen receptor‐sexual hormone binding globulin . A great challenge is to identify how these molecular players are expressed in discrete sperm subpopulations.…”