Transcription Factor Yin Yang 1 Involves in Insulin Resistance-Polycystic Ovarian Syndrome by Regulating Sex Hormone Synthesis and Wnt/β-Catenin Signaling Pathway

Abstract

Polycystic ovary syndrome (PCOS) is a common metabolic disorder affecting up to 15% of reproductive-aged women. Insulin resistance (IR) is considered to be the main cause of PCOS since it disrupts both the endocrine system to affect normal ovulate and induces hyperandrogenism. Therefore, to understand the underlying mechanisms on specific pathogenesis of IR is critical for IR-PCOS treatment. Here we discovered that transcriptional factor Yingyang 1 (YY1) was elevated in IR-PCOS patients comparing to non-IR-PCOS patients, and YY1 expression level highly correlated to multiple clinical characteristics of IR-PCOS patients. We confirmed this finding in an IR-PCOS rat model, in which high YY1 expression and abnormal expressions of several other key molecules were related to IR and sex hormone synthesis. To further explore the transcriptome changes and more detailed mechanisms on how YY1 contributed to IR-PCOS, a high-throughput RNA-sequencing was performed and analyzed. Knock-down of YY1 in COV434 cells affected multiple signaling pathways including endocrine, metabolic, progesterone and oocyte maturation. Among these, 18 genes tightly related to IR were identified. Collectively, our data clearly showed transcriptional factor YY1 is critical for developing IR-PCOS by regulating multiple metabolic and endocrine pathways. Funding: These studies were supported by the National Natural Science Foundation of China (Grant No. 81560245). Declaration of Interest: The authors have no conflicts of interest to declare. Ethical Approval: All procedures were approved by Ethics Committee of the first affiliated hospital of Guangxi medical University and The Third Affiliated Hospital of Sun Yat-sen University. The clinical data are acquired from medical record system and informed consents were approved and signed by each recruited patient.