Follicle stimulating hormone receptor: impact of genetic variations and gene expression levels in fertility

Abstract

To date, Assisted Reproductive Technologies (ARTs) increase the probability of conception starting from the collection of more than a single oocyte produced in a regular ovulatory cycle. To achieve this aim many ovarian stimulation protocols have been proposed, some with very good performances but also with some important side effects and, more important, with not many possibilities to personalize the hormonal treatment according to patients characteristics. Although the hormonal and clinical parameters remain the only proven factors to aid in the selection of the best possible hormone stimulation for each patient, none of the commonly used markers has an optimal predictive value if considered individually. Therefore, a complementary strategy that is emerging in recent years is pharmacogenetics. The candidate genes to date are follicle hormone (FSH) and its receptor (FSHR), in which single nucleotide polymorphisms (SNPs) are able to modulate the expression and functions of the genes. The FSH-FSHR complex initiates a cascade of molecular events in the gonads, from the increase of cyclic AMP (cAMP) to the transduction of enzyme-encoding mRNA products, which modulate the synthesis of steroid hormones. In this way, FSH stimulates folliculogenesis and steroidogenesis in the ovary and testicular development and spermatogenesis in the testis. The administration of FSH in the treatment of infertility, in both sexes, aims to induce these activities in order to allow infertile couples to carry out the pregnancy. Many studies on the genetic polymorphisms of FSH and its receptor identified which of these variants could be considered as a marker able to predict the individual responses of patients undergoing ovarian stimulation. KEY WORDS: Clinical embryology, FSH, Polymorphism, Ovarian functions.