Intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome via activating macrophage-angiogenesis-related androgen signaling

作     者：MIN CHEN YUAN HUANG WEN XU CHUNLIN SU 

作者机构：Renji Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai200232China The Obstetrics and Gynecology Hospital of Fudan UniversityShanghai200232China 

出 版 物：《BIOCELL》 (生物细胞（英文）)

年 卷 期：2022年第46卷第6期

页      面：1505-1519页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This research was supported in by the National Natural Science Foundation of China(Grant No.81701409) Natural Science Foundation of Shanghai of China(Grant No.12ZR441400) 

主　　题：Polycystic ovary syndrome Androgen Adipose tissue Angiogenesis Macrophages 

摘      要：The development of polycystic ovary syndrome(PCOS)is closely related to the chronic inflammatory and *** studies have found macrophages regulate the chronic inflammation and adipose tissue remodelling,but the underlying mechanisms have not been *** this study,we established a model of PCOS in the offspring rats by high androgen exposure during late pregnancy in parental and established a female rat macrophage eliminating model by rejection of clodronate ***,the offspring rat macrophage phenotype in offspring female rat adipose tissue,and levels of testosterone,angiogenic factors(PDGF and VEGF)and inflammatory factors(TNF-αand MCP-1)were *** coculture of RAW264.7 macrophage with adipocytes or C166 endothelial cells(ECs),the mobility of adipocytes,and the ECs function with associated signalling pathway were detected by using of androgen inhibitor Apalutamide,NF-κB inhibitor JSH-23 and ERK1/2 inhibitor *** was found that high androgen exposure during late pregnancy led to increased testosterone levels and overweight and obesity,increased size and reduced number of subcutaneous and intra-abdominal adipocytes,and increased secretion of TNF-αand MCP-1 in female rats in the *** macrophages significantly increased adipocytes and angiogenesis in offspring of rats with intrauterine high androgen,and reduced TNF-αand *** promoted mobility of adipocytes,and inhibited proliferation,migration,tube formation of ECs under hyperandrogenic condition,which were significantly inhibited by Apalutamide,JSH-23 and ***,intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome through increasing M1 differentiation of pro-inflammatory macrophages and activating VEGF-related angiogenesis via androgen/NF-κB/ERK1/2 signalling pathway.