Abstract
The purpose of a pharmacogenomic approach is to tailor treatment on the basis of an individual human genotype. This strategy is becoming increasingly common in medicine, and important results have been obtained in oncologic and antimicrobial therapies. The rapid technological developments and availability of innovative methodologies have revealed the existence of numerous genotypes that can influence the action of medications and give rise to the idea that a true “individualized” approach could become in the future a reality in clinical practice. Moreover, compared to the past, genotype analyses are now more easily available at accessible cost. Concerning human reproduction, there is ample evidence that several variants of gonadotropins and their receptors influence female reproductive health and ovarian response to exogenous gonadotropins. In more detail, variants in genes of follicle-stimulating hormone β-chain (FSH-B) and its receptor (FSH-R) seem to be the most promising candidates for a pharmacogenomic approach to controlled ovarian stimulation in assisted reproductive technologies. In the present review, we summarize the evidence regarding FSH-B and FSH-R variants, with special reference to their impact on reproductive health and assisted reproductive technology treatments.
Highlights
Follicle-stimulating hormone (FSH) is a pituitary gonadotropic hormone, which is fundamental for follicle growth in females and spermatogenesis in males
Acidic isoforms seems to be involved in follicular recruitment at the end of menstrual cycles, while follicle selection and rupture seem to be promoted by basic FSH isoforms [9]
The search strategy consisted in the use of the combinations of the following keywords: “controlled ovarian stimulation,” “assisted reproductive technology (ART),” “IVF,” “ICSI,” “FIVET,” “IUI,” “intrauterine insemination,” “ovulation induction,” “ovarian stimulation,” “polymorphism,” “single nucleotide variants (SNV),” “Single nucleotide variant,” “FSH Receptor,” “FSHR,” “FSH,” “follicle-stimulating hormone,” “follicle-stimulating hormone,” and “beta subunit.”
Summary
Follicle-stimulating hormone (FSH) is a pituitary gonadotropic hormone, which is fundamental for follicle growth in females and spermatogenesis in males. FSH, when in the ovary and testis, binds to its cognate receptor (FSH-R), which belongs to the superfamily of the G-protein coupled receptors It is characterized by a long ligand-binding extracellular domain, seven transmembrane domains, mediating the hormonal stimulus, and an intracellular C-terminal domain participating in receptor internalization and desensitization of the signal. It promotes folliculogenesis by stimulating estradiol production by the aromatase enzyme system, stimulating granulosa cell growth and inducing the expression of luteinizing hormone receptors [1]. Together with LH, FSH levels peak in the mid-cycle which induces important actions in the ovulation process, such as the stimulation of proteolytic enzymes essential for follicular wall rupture [7]. Acidic isoforms seems to be involved in follicular recruitment at the end of menstrual cycles, while follicle selection and rupture seem to be promoted by basic FSH isoforms [9]. We will summarize the most important evidence concerning variants of FSH and FSH-R and their implication in female reproductive functions
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