Receptor Study
A lot of understanding in the biological process of living organisms has changed the way we see life. Cells organize into a wide variety of tissues, a group of tissues together with the immune and hormonal system form a whole living organism. A large number of molecular and biochemical interactions called pathways occur in every cell of a tissue to perform its function. A complex biochemical pathway inside a cell begins with the binding of a ligand to its receptor.
Different types of receptors are broadly classified into two types a) intracellular receptors b) cell surface receptors. Cell surface receptors are further classified into different categories. G-protein coupled receptors of the cell surface receptors family play a very important role in reproductive medicine. Follicle-stimulating hormone receptor and Luteinizing hormone/choriogonadotropin hormone receptor are two important receptors of reproductive medicine that represent the G-protein coupled receptors.
The follicle-stimulating hormone binds with follicle-stimulating hormone receptor, its activation is important for the FSH function. FSHR is expressed in the ovary, testis, and uterus. Both LH and hCG binds with LHCGR. LHCGR is expressed in the ovary, testis, and extragonadal organs like the uterus.
Genetic variants like mutations, insertions/deletions, and single nucleotide polymorphisms in the gonadotropins (FSH, LH, and hCG) and their receptors’ genes may lead to infertility and its related disorders in both males and females. The genetic variants influence the parenthood attempts at a later age in life and create a situation in life that women fail to conceive naturally making advanced fertility treatments like IUI, IVF/ICSI, etc necessary for the couple to achieve parenthood.
For many infertile couple’s assisted reproduction holds the key for parenthood. The outcome of assisted reproduction is greatly influenced by the effectiveness of controlled ovarian stimulation (COS). whereby exogenous gonadotropins(FSH & LH) are administered to induce folliculogenesis, the aim is to obtain a suitable high number of mature oocytes so that the most viable embryo can be selected for transfer. However, the response to COS varies widely from woman to woman, with up to 24% experiencing a poor response and others at risk of an excessive response (ovarian hyperstimulation syndrome [OHSS]). It is currently difficult to predict poor response, and the mechanisms leading to poor ovarian reserve are particularly unclear in young women. there is a need for personalized COS that will maximize the chances of success for each woman. Individual genetic variability is known to affect the outcome of COS, and the potential for customizing therapy based on the patient’s genome has been investigated. A pharmacogenomic approach may particularly help to match individual women to their optimum COS protocol. Mutations are rare, but polymorphisms in the coding and non-coding regions are common in the normal population. Polymorphisms in coding regions of FSH-R and LHCG-R genes are more studied compared to polymorphisms in the noncoding regions, resulting in variation in the activity that can lead to subfertility and influence the response to the various fertility treatments and their outcome.
Currently, genetic screening is not a routine part of the IVF treatment process. However, polymorphisms have been identified in the genes for key reproductive hormones that identify women at risk of a poor response to COS. Genotyping for polymorphisms in reproductive hormones and their receptors in women before the initiation of IVF treatment will help identify those who need tailored treatment regimens. Such a pharmacogenetics approach will facilitate the matching of all women to the optimum COS protocol for each individual. A candidate gene approach may help to determine the predictive value of some of the already published genetic variations and other novel predictive genetic markers. Once genetic markers are established, these may be included in novel predictive algorithms that could be used to help guide patient management.
