Studies On The Role Of Androgen In Pathogenesis Of PCOS

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting young women of reproductive age with a prevalence7.4%in this age group of Chinese women. As the most common cause of anovulatory infertility, PCOS affects51%of oulatory infertility patients. Polycystic ovarian syndrome have the high heterogeneity and long-term risk of complications including menstrual dysfunction, infertility, hirsutism, acne, obesity, and metabolic syndrome in clinical.Women with this disorder have an established increased risk of adverse sequelae that include dyslipidemia, atherosclerosis, insulin resist-ance and type2diabetes (T2D). The pathogenesis of PCOS is not fully understood. Genetic traits as well as environmental factors are implicated in the pathogenesis of the syndrome. The mechanism of the environmental factors in the pathogenesis of PCOS is unknown. Many female mammals (rhesus monkey,sheep,rats,mouse and so on) exposed to androgen excess in utero or during early post-natal life typically show a permanent PCOS-like phenotype characterized by ovarian and adrenal hyperandrogenism, neuroendocrine dysfunc-tion manifesting as LH hypersecretion, central obesity and insulin resistance. The phenomenon has been formulated as the fetal origin of PCOS hypothesis, which intends to give a possible explanation for PCOS aetiology. But mechanism of the hypothesis is unknown. Given that the epigenetic modifications are usually involved in the development and inheritance of many adult diseases with fetal origin, emerging data also implicate epigenetic changes in fetal life in the developmental origins of PCOS. Epigenetics is the study of heritable changes to the environment information pass by hormones, growth factors and other regulatory molecules in gene expression that are not caused by DNA sequence alterations but are mitotically and transgenerationally heritable. Eigenetics change is reversible which is different from DNA variation, and it provides an optimistic outlook for the treatment of diseases. DNA methylation, the principal mechanism of epigenetics, has been reported to play a role in cancer, aging, and complex chronic diseases.To investigate the methylation situation of PCOS, we conducted a methylation chip, screening the diffscore gene between patients with PCOS and matched controls. And high LH level and hyperandrogenism are well known as PCOS typical pathophysiologic abnormalities. Therefore, we decide to detect DNA methylation patterns of LH,LHR and SHBG genes in PCOS patients and matched controls and hope to get some new thoughts about the pathogenesis of PCOS. And we find the methylation patterns of LHR gene have significant difference between PCOS patients and matched controls in granulose cell of ovary.Because of collect specimens of human is difficult,and in order to further discuss whether the abnormal methylation patterns of LHR gene is caused by the environment of utero, we decide to detect DNA methylation patterns of LHR gene in the mouse exposure to androgens in utero. We find that the methylation patterns have significant difference between experimental group, solvent (soybean oil) control group and blank control group.