Distribution and function of FSH receptor genetic variants in normal men

Abstract

Follicle stimulating hormone (FSH) plays a key role in the maintenance of qualitatively and quantitatively normal spermatogenesis. It controls gamete development through Sertoli cells, via binding to its receptor. The influence and importance of FSH receptor (FSHR) variants on Sertoli cell function is not completely understood and remains to be investigated. In this retrospective study, we explored the impact and action of two distinct FSHR isoforms, Thr307/Asn680 and Ala307/Ser680, in a large group of men. This investigation includes 288 normal healthy men, 86 of whom were proven fathers previously studied, and 202 were newly recruited subjects. The FSHR polymorphism at position 680 was analyzed in the whole group, while position 307 was investigated in 150 subjects, both of them by single-stranded conformation polymorphism (SSCP) gel electrophoresis. The distribution frequency for position 680 was 29% for the Asn/Asn, 52% for the Asn-Ser, 19% for the Ser-Ser variant, and for position 307, 27% for the Thr-Thr, 55% for the Ala-Thr, 18% for the Ala-Ala, respectively. Polymorphism combinations that were different from Thr307/Asn680 - Ala307/Ser680 were found in four subjects. When subjects were grouped according to genotype at position 680, no significant differences between basal FSH, testosterone, inhibin B levels and semen parameters were found. This clinical finding demonstrates that, differently from females, in whom a significant correlation between FSHR polymorphism and basal FSH levels was found, the FSHR genotype has no influence on clinical parameters in males.

Effects of polymorphisms in gonadotropin and gonadotropin receptor genes on reproductive function

“…Since the FSHR genotype is responsible for some differences in the FSH dose needed for stimulation in women [19,38] and in transcriptional activity in vitro [114], several studies have been conducted to verify possible differences in men. However, the common FSHR polymorphism Asn680Ser showed no effect on serum FSH levels and other clinical parameters in men [18,115], leading to a discrepancy between the two genders which still remains unexplained. In men, several investigations on the distribution of G-29A, A919G and A2039G FSHR SNPs were made, producing various and sometimes contradictory results [18,[116][117][118] and suggesting that some polymorphisms lead to testicular dysfunction only when in association with a particular genetic background or environmental factors.…”

Association between follicle-stimulating hormone receptor polymorphisms and reproductive parameters in young men from the general population

“…The genotype distribution of the polymorphism in position 680 differs according to ethnicity so that the homozygous Ser680 genotype is more uncommon in Asia than among Europeans, whereas the homozygous Asn680 genotype is clearly over-represented in Asian populations [8]. Two uncommon allelic combinations, Thr307/Ser680 and Ala307/Asn680, are present in less than 5% of populations of European and Asian origin [9,10].…”

“…The allelic variants of the FSHR have been reported to be similarly distributed in fertile and infertile men [14][15][16], and no differences in sperm and testicular parameters were noted between fertile controls and infertile men, subdivided according to FSHR genotype [6,9,17,18]. In contrast, some studies have shown differences in the FSHR genotype distribution among fertile controls and infertile men [18][19][20].…”

<i>FSHR</i> Gene Polymorphisms Causes Male Infertility

“…Other investigations, however, found significant variations of SNP distributions, and suggested that ethnic differences could be involved in polymorphism-related infertility [29]- [32]. In some previous studies, the G-29-A919-A2039 haplotype was shown to be more prevalent in normozoospermic men than in azoospermic patients (38.4% vs. 33.9%, respectively; chi (2) test, P = 0.045), indicating that this haplotype may be a protective factor against male sterility [33].…”