Impact of follicle-stimulating hormone receptor variants in female infertility

Abstract

Purpose Follicle-stimulating hormone (FSH) and its receptor play a major role in the development of follicles and regulation of steroidogenesis in the ovary and spermatogenesis in the testis. We aim to analyze the role of FSHR gene variants (single nucleotide polymorphisms (SNPs) in exon 10 (codon 307 and 680) and in the core promoter region (at position −29) and Ala189Val inactivating mutation) in Turkish infertile women. There were studies analyzing the effects of the SNPs in exon 10 (codon 307 and 680) and in the core promoter region (at position −29) of the FSHR gene on spermatogenesis, but to our knowledge, there were no studies analyzing the effects of these three SNP combinations on female fertility. Methods In this study, the allelic, genotype, and haplotype frequency distributions of these three SNPs in the FSHR gene were analyzed in 102 infertile women and 99 unrelated healthy control individuals. The distribution of the polymorphisms was conformed by Hardy-Weinberg equilibrium test. Results There were no statistical differences (P>0.05) in the allele, genotype, and haplotype frequencies of the polymorphisms and FSH, luteinizing hormone (LH), estradiol (E2), and prolactin (PRL) levels between the infertile patients and the controls. However, a significant relation was found between 307 SNP GA genotype and FSH level ≥12. We did not find any homozygous or heterozygote mutations in infertile patients and healthy fertile controls. Conclusion The present study was the first study analyzing gma mutation and the polymorphism of the FSHR core promoter at position −29 alone and in combination with the two common SNPs in exon 10 in Turkish infertile women population. These findings indicate the significance of Ala307Thr GA genotype may be a predictive marker for poor ovarian reserve and infertility.

Association of a promoter polymorphism in FSHR with ovarian reserve and response to ovarian stimulation in women undergoing assisted reproductive treatment

“…In a further study of 100 Indian women, homozygosity for the variant was also associated with inadequate ovarian response (Desai et al, 2011). A Turkish study of 102 infertile females found no relation between this variant and baseline FSH concentrations (Ilgaz et al, 2015).…”

TGF-β signaling controls FSHR signaling-reduced ovarian granulosa cell apoptosis through the SMAD4/miR-143 axis

“…In ovaries of mammals, FSHR interacts with its ligand follicle-stimulating hormone (FSH) and has a crucial role in follicular development, steroidogenesis, and female infertility. 1, 2, 3, 4 In pigs, Sato et al 5, 6 detected a quantitative trait loci (QTL) for the number of corpora lutea on SSC3 with genome-wide significance in an F2 resource population by crossing a Duroc boar with a Meishan sow, and further identified FSHR as a functional gene for this QTL by fine mapping, association, and mutational analyses. Maturation-dependent regulation of FSHR expression occurs in adult porcine ovaries.…”

Association of estrogen, progesterone and follicle stimulating hormone receptor polymorphisms with in vitro fertilization outcomes

“…Single nucleotide polymorphisms (SNPs) in any of these three genes, or in combination, could modify hormone action and the endocrine feedback systems (Ilgaz et al 2015). This could result in interindividual variation in reproductive performance which in turn could influence the success of the assisted reproductive techniques, like in vitro fertilization (IVF), which are popular treatment options for infertile couples.…”