Pharmacogenomic Biomarkers of Follicle-Stimulating Hormone Receptor Malfunction in Females with Impaired Ovarian Response—A Genetic Survey

Abstract

Follicle-stimulating hormone receptor (FSHR) plays an essential role as one of the most important molecules in response to some of infertility related medications. Impaired ovarian reserve and poor response to such treatments are partially dependent on the FSHR molecule itself. However, the function and drug sensitivity for this receptor may change due to various allele and polymorphisms in the FSHR gene. Studies indicated some of the FSHR-mediated treatments utilized in clinical centers display different outcomes in specific populations, which may arise from FSHR altered genotypes in certain patients. To support the increased demands for reaching the personalized drug and hormone therapy in clinics, focusing on actionable variants through Pharmacogenomic analysis of this receptor may be necessary. The current study tries to display a perspective view on genetic assessments for Pharmacogenomic profiling of the FSHR gene via providing a systematic and critical overview on the genetics of FSHR and its diverse responses to ligands for infertility treatment in females with impaired ovarian responses and show the potential effects of the patient genetic make-up on related binding substances efficacy. All identified functional drug-related alleles were selected through a comprehensive literature search and analyzed. Advanced technologies for the genetic evaluation of them are also discussed properly.

Effects of FSHR and FSHB Variants on Hormonal Profile and Reproductive Outcomes of Infertile Women With Endometriosis

“…Accumulating evidence suggests that a number of single nucleotide variants (SNVs) in genes involved in FSH signaling, estrogen biosynthesis, folliculogenesis, and folate metabolism, in association with other factors, can influence the ovarian response to exogenous gonadotropins in assisted reproductive treatment (ART) ( 8 , 9 ). Therefore, the molecular biology of the triggered cellular pathways for these medications has attracted more attention in clinical investigations ( 10 ). Among the variants in the coding region of FSHR , two (c.919G>A, p.Ala307Thr and c.2039G>A, p.Ser680Asn) have been extensively studied in ART protocols to evaluate the stimulation of FSH receptors by gonadotropins ( 11 ).…”

Role of FSHR gene (rs6165) polymorphism in ovarian stimulation by exogenous FSH of Iraqi infertile women

“…Several parameters such as age ,lowed ovarian reserve and serum level of AMH have been used as an indicator to estimate the ovarian response but FSHR are more extensively studied in connection to ovarian response in different people (4). FSH-R is type of G-protein coupled receptor that belong to glycoprotein hormone receptor family with along extracellular domain ,which consist mainly from seven transmembrane domain ,three of which are short intracellular loops, three extra loops and an intracellular tail (5).On chromosome 2p21 the human FSHR gene is located and it is single copy gene that composed from 54 Kb in length. FSH is crucial for promoting follicular growth throughout the process of folliculogenesis and it is action is mediated by FSHR ( 6).Genetic disorders caused by mutation in FSH receptor which effect on it by gain or loss of it is function (7).However ,many SNPs have been found in the gene of FSHR , some of these SNPs are extremely common .…”