Association Between Follicle-Stimulating Hormone Receptor (FSHR) rs6166 and Estrogen Receptor 1 (ESR1) rs2234693 Polymorphisms and Polycystic Ovary Syndrome Risk, Phenotype, and Reproductive Outcomes in an Infertile Portuguese Population

Abstract

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often leading to anovulatory infertility. PCOS pathophysiology is still unclear and several potential genetic susceptibility factors have been proposed. The effect of polymorphisms in two genes related to follicular recruitment and development, the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor 1 (ESR1), have been studied in different populations with contradictory results.Aims: To evaluate the influence of FSHR rs6166 (c.2039A>G) and of ESR1 rs2234693 (Pvull c.453-397 T > C) polymorphisms on PCOS risk, phenotype, and response to controlled ovarian stimulation (COS).Materials and methods: Genotyping of the FSHR rs6166 and the ESR1 rs2234693 polymorphisms was performed in PCOS women and a control group undergoing in vitro fertilization (IVF). Demographic, clinical, and biochemical data, genotype frequency, and IVF outcomes were compared between groups.Results: We evaluated 88 PCOS women and 80 controls. There was no significant difference in the genotype distribution of FSHR rs6166 polymorphism between PCOS women and controls (AA 31.8%/AS 48.9%/SS 19.3% in PCOS women vs AA 37.5%/AS 40.0%/SS 22.5% in controls; p = 0.522). The same was true for the ESR1 rs2234693 (CC 24.1%/CT 46.0%/TT 29.9% in PCOS women vs CC 18.8%/CT 48.8%/TT 32.5% in controls; p = 0.697). In PCOS women, we found higher follicle-stimulating hormone (FSH) levels on the third day of the menstrual cycle associated with the SS variant of the FSHR polymorphism (9.2 vs 6.2 ± 1.6 and 5.6 ± 1.6 mUI/mL; p = 0.011). We did not find other associations between the baseline hormonal parameters, antral follicle count, and response measures to COS with FSHR or ESR1 genotypes. We found, however, a need for higher cumulative doses of FSH for COS in patients with the SS variant of the FSHR rs6166 polymorphism (1860.5 ± 627.8 IU for SS vs 1498.1 ± 359.3 for AA and 1425.4 ± 474.8 for SA; p = 0.046 and p = 0.046). Conclusion: Our data suggest that in the population, FSHR rs6166 and ESR1 rs2234693 polymorphisms do not influence the risk of developing PCOS nor do they influence the patient's phenotype and IVF success. However, the SS variant of the FSHR rs6166 polymorphism may be associated with FSH resistance requiring higher FSH doses for COS.

The Identification of RPL4 as a Hub Gene Associated with Goat Litter Size via Weighted Gene Co-Expression Network Analysis

“…Reproductive traits are complex quantitative traits encompassing important indicators such as litter size and ovulation rate, which are regulated by major effect genes and multiple minor effect genes, often referred to as reproductive genes [18,19]. Through traditional molecular marker techniques such as restriction fragment length polymorphism (RFLP), microsatellites, and single nucleotide polymorphisms (SNPs), some major effect genes such as progesterone receptor (PGR), estrogen receptor (ESR), follicle-stimulating hormone (FSHR), prolactin receptor (PRLR), etc., have been identified [20][21][22]. It is not difficult to find that these genes are more or less related to the regulation function of the neuroendocrinereproductive system and have significant impacts on reproductive performance.…”