Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

Abstract

Background:DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS.Methods:Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls. Ovary GCs were extracted from in vitro fertilization embryo transfer. Methylation status of YAP1 promoter was detected by bisulfite sequencing PCR (BSP). Protein and mRNA expression of YAP1 were measured by western blotting and real-time quantitate PCR.Results:Overall methylation level of YAP1 promoter region from PCOS group was significantly lower than that from control group. CpG sites analysis revealed that 12 sites (−443, −431, −403, −371, −331, −120, −49, −5, +1, +9, +15, +22) were significantly hypomethylated in women with PCOS (P < 0.05). A significant upregulation of YAP1 mRNA and protein expression levels was observed. Testosterone concentration could alleviate the methylation status and demonstrate obvious dose–dependent relation.Conclusion:Our research achievements manifest that hypomethylation of YAP1 promoter promotes the YAP1 expression, which plays a key role in the pathogenesis and accelerate PCOS.

Hippo signaling in the ovary and polycystic ovarian syndrome

“…Their study also indicated that the alleles are associated with insulin sensitivity and resistance and LH levels, further validating the association with clinical PCOS. Additionally, aberrancy in YAP1 methylation patterns among patients with PCOS has been demonstrated by Jiang et al [44]. Although our pilot study did not demonstrate differential expression of LATS1 among PCOS patients and controls, Sun et al [45] found that a deletion in Lats 1 resulted in ovarian germ cell apoptosis and follicular cysts.…”

Aberrant Promoter Methylation of YAP Gene and its Subsequent Downregulation in Indian Breast Cancer Patients

“…Promoter hypermethylation of critical growth regulators like tumor suppressor genes and its subsequent transcription silencing plays a pivitol role in causing cancer [ 31 ]. A recent study demonstrated hypomethylation of YAP promoter promotes the expression of YAP in polycystic ovary syndrome [ 32 ]. However, methylation status of YAP promoter in breast cancer is not yet known.…”

Impact of Smoking and Alcohol Consumption on Oxidative Status in Male Infertility and Sperm Quality

“…Among 257 participants, 124 fertile men were considered as controls and 133 were primary infertile men. Total participants were divided into different groups according to their smoking and/or drinking habits such as, fertile control subjectssmokers (29), alcohol drinkers (33), smokers+alcohol drinkers (34) and total abstainers (who never smoked or drank alcohol before 28), Infertile subjects-smokers (30), alcohol drinkers (34), smokers+alcohol drinkers (37) and total abstainers (32; fig. 1).…”

“…The male reproductive hormones in serum samples were measured using Cobas e411 analyser with platform electrochemiluminescence immunoassay technique (Roche Diagnostics, Mannheim, Germany) and the normal range for LH, FSH, testosterone, and prolactin hormones were 4-11 mIU/ml, 2-10 mIU/ml, 2-12 ng/ml and 2-18 ng/ml, respectively [29] .…”