Evaluation of DNA methylation pattern in TLR۲ gene promoter in blood samples derived from PCOS patients

Background and Aim: Polycystic ovary syndrome (PCOS) is the leading endocrine and metabolic disorder in women of reproductive age, with a prevalence of ۶-۱۰% and the major cause of an ovulatory infertility. This women characterized by hyperandrogenism, abnormal development of ovarian follicles and increase in follicles number. To date, the PCOS is heterogeneous disorder and unclear and has been related to insulin resistance, obesity, type۲ diabetes mellitus, cardiovascular disease, infertility and some malignancies such as endometrial, carcinoma and also breast and ovarian cancer among other morbidities. Substantial evidence illustrates the impact of genetic intrauterine and environmental factors on the PCOS etiology. Epigenetic mechanisms may contribute to PCOS. Epigenetic is a phenomenon can cause phenotype or gene expression difference without DNA sequence alteration, therefore in present study TLR۲ gene was candidate which its gene not only is essential of innate immune system but due to good quality fertilization. However, the expression and function of innate immune cell-related genes in non-immune cells within the ovary has been reported recently and provides a novel and important regulatory system during ovulation. Several member of the Toll-Like receptor (TLR) surveillance system are expressed in granulosa cells and cumulus cells. These receptors can be activated by pathogens as well as endogenous ligands leading to the induction and release of potent cytokines and chemokine from cumulus cells. These inflammatory factors exert potent effects on cumulus cells, oocyte, expansion, ovulation, transport and fertilization indicating that ovulation is a more complex immune-inflammatory process than previously recognized Methods: In this research DNA methylation of TLR۲ gene promoter was assayed on peripheral blood samples of ۵۰ PCOS and ۵۰ healthy casas. After genomic DNA extraction and its bisulfite treatment. Design primer for CpG-۳ in TLR۲ gene promoter by using methprimer online software and MS-PCR was performed on treated DNA Results: DNA methylation (hyper methylation) presented in ۴۱(۸۲%) of patient group and ۰(۰%) in control group. There was significant difference between two groups using of Chi-squre test (P<۰.۰۰۱)Conclusion: This study results supports involvement of DNA methylation of TLR۲ gene promoter in PCOS. However, additional studies using quantitative methods are suggested to confirm this result.

کلیدواژه ها:

Epigenetic ، Polycystic ovary syndrome ، Ovulation ، MS-PCR ، Hyperandrogenism