Combined Effects of the FSHR 2039 A/G and FSHR -29 G/A Polymorphisms on Male Reproductive Parameters

Abstract

A single nucleotide polymorphisms (SNPs) on the male reproductive function in a cohort of Sicilian men. Materials and Methods: Materials and Methods: One-hundred thirty Sicilian men were enrolled and underwent blood withdrawal for hormone measurement and FSHR 2039 A/G and FSHR-29 G/A SNP genotyping, testicular volume evaluation by ultrasound scan, and semen analysis. A meta-analysis of the FSHR-29 G/A SNP, evaluated in a previous study of the Sicilian population was done. Results: Results: No genotype of the FSHR 2039 A/G SNP correlated with serum follicle-stimulating hormone (FSH) levels, testicular volume, sperm concentration, and total sperm count. In contrast, normozoospermic men with FSHR-29 GG and FSHR-29 GA genotypes had significantly lower sperm concentrations compared to men with the FSHR-29 AA genotype. The other sperm parameters did not show any significant difference. The meta-analysis showed no significant difference in serum FSH levels, testicular volume, sperm concentration, and total sperm count between FSHR-29 GG and FSHR-29 AA in Sicilian men. No difference was found even when the two SNPs were evaluated in combination. However, this combination was present, as expected, only in a low proportion (3.8%) of the men studied. Conclusions: Conclusions: The SNPs FSHR 2039 A/G and FSHR-29 G/A in combination did not seem to have any effect on male reproductive function in a cohort of Sicilian men. The effect of these SNPs has only been studied in granulosa cells so far. Further studies on their role in Sertoli cells are needed.

Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion

“…In recent years, there have been a number of articles on the role of SNPs in the FSHR genes, some of which have shown that the two very common SNPs at positions 307 and 680 in the 10th exon of the FSHR genes are known to influence the efficiency of signal transduction and are closely related to the ovarian response to in-vitro fertilization (IVF) in the clinic [ 110 , 111 , 112 , 113 ]. In addition, studies on granulosa cells have confirmed that the SNPs of FSHR are associated with the transcription activity of the promoter and the binding capacity of FSHR with FSH [ 114 ].…”

Effects of Follicle-Stimulating Hormone on Human Sperm Motility In Vitro

“…A pioneering study on hypophysectomized rats has shown, after treatment with hpFSH and/or testosterone, that while FSH sustains the proliferative phase of spermatogenesis, testosterone plays a role in the differentiation phase from spermatid to spermatozoon [ 22 ]. However, FSH is administered to oligozoospermic patients within normal FSH serum levels (in Italy, the cut-off for FSH prescription is <8 mIU/mL), and meta-analytic studies indicate dose-dependent effectiveness not only on sperm concentration and total sperm count but also on progressive motility [ 23 ]. FSH treatment seems to improve sperm DNA fragmentation as well [ 24 ].…”

Follicle‐stimulating hormone beta subunit and receptor variations in infertile men in Central Black Sea Region of Turkey

“…It has been also shown that the haplotypes formed by the FSHR 2039A>G with other FSH receptor variants may be associated with spermatogenic failure (Lend et al, 2010; Wu et al, 2017). However, Cannarella et al (2020) evaluated FSHR genotypes alone or combined in Italian men and they showed no significant difference among genotypes in terms of serum FSH and semen parameters (Cannarella et al, 2020). Indeed, FSHR 2039A>G exhibits a high degree of linkage disequilibrium with another variant, FSHR c.919A>G (rs6165) which also identified in exon 10 of FSHR gene (Schubert et al, 2019; Simoni & Casarini, 2014).…”

“…Follicle-stimulating hormone (FSH) plays an important role in fertility and its maintenance is regulated along with other endocrine factors. FSH regulates gametogenesis and steroidogenesis by binding FSH receptor (FSHR) in gonads (Cannarella et al, 2020). FSH stimulates the proliferation of testicular Sertoli cells in the foetal, neonatal and pubertal periods.…”