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.
Highlights
FSHR, Related Infertility Medicines, and the Role of PharmacogeneticsFollicle-stimulating hormone receptor (FSHR) is a rhodopsin-like receptor, which belongs to the G-protein-coupled receptors (GPCR) superfamily, and consists of an intracellular domain and a large leucine-rich repeat extracellular domain and passes seven times through the cellular membrane [1]
Most of the genetic variations for the FSHR gene are defined as single nucleotide variants (SNVs), and because of that, many of them could be included in genome-wide array-based genotyping (Infinium BeadChips from Illumina) and/or specified custom SNP array chips as part of infertility genetic profiling for the related patients (Affymetrix Axiom array) [48]
While it is in the end, oocyte quality which is the most important parameter and that is no doubt affected by a plethora of factors and resulted in different treatment outcomes, but FSHR genotyping is still considered as a promising PGx approach for personalized infertility therapy in women, who receive the related medicines and displayed negative efficiency [72], especially, when there are no other common reasons for nonsuccessful infertility therapy procedures
Summary
Follicle-stimulating hormone receptor (FSHR) is a rhodopsin-like receptor, which belongs to the G-protein-coupled receptors (GPCR) superfamily, and consists of an intracellular domain and a large leucine-rich repeat extracellular domain and passes seven times through the cellular membrane [1]. Many FSHR associated treatments like synthetic or natural derived follicle-stimulating medicines, gonadotropins, and ovarian stimulation drugs such as clomiphene and metformin are used for infertility treatment in females [6] These drugs are used in assisted reproductive technologies (ART) to stimulate multiple follicles, which need the medications to collect, to develop, and to maturate eggs with different dosages and usage protocols [7]. Molecular biology of the triggered cellular pathways for these medications turned to more attention in clinical investigations From this point of view, FSH and other related medicines as the specific ligands bind to FSHR, leading to start the signal transduction pathways in target cells (granulosa cells in females). Ttohiassrseovcieiawtepdrolivgidanesdas cdruitircianlganindfesyrtsitleitmyattriecaatnmaleynstisinof females wthitehgiemnpetaicirbeadsiosvfaorriFaSnHrResaenrvdethbeecfuauncsteioonfapl oaloterrraetsiopnosndsueetotoFvSaHrioaunsdalFleSlHesRinrethlaetegdesetfifmecutslaotfonfsrtetohsimmm.eaImuenle,lasraotewodnsrudistrl.hiettiIliinnaomgtnaepid,dnadtihrddieteiirdvourenoegr,vslsatea’htrreeeieadfsrnfipeccrloaeeantslcelseyudervslacaeterrobellpeaudcsalaasitsuorhccswpuieaasaottsehyfedwpdgolai.eogynrTaegrnhesedesnaspelrodasenutaeslrriesiesntttgloeiidsdFitne,SefndHaet,nritaafidinlniedtdtdyhFtetfhSruHeepnaoRptcmtotretieeneolnnatnitttaaeiiadllnl alleles foreftfheectFsSoHf tRhegmenoenarreelaatnedalydzruegds,’aenffdicaacdyvaarneceddisctuecsshendo. lTohgeielsatfeosrt gideennettifiicedevfaulnucatitoionnal of them aarelleilnetsrfoodruthceedFSaHsRwgeelnl.e are analyzed, and advanced technologies for genetic evaluation of them are introduced as well
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