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

Biocell

article

MIN CHEN¹  YUAN HUANG²  WEN XU²  CHUNLIN SU² 

[1] Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine;The Obstetrics and Gynecology Hospital of Fudan University

关键词: Polycystic ovary syndrome;    Androgen;    Adipose tissue;    Angiogenesis;    Macrophages;   

DOI  :  10.32604/biocell.2022.016564

学科分类：仪器

来源: Biocell

【 摘 要 】

The development of polycystic ovary syndrome (PCOS) is closely related to the chronic inflammatory andobese. Recent studies have found macrophages regulate the chronic inflammation and adipose tissue remodelling, butthe underlying mechanisms have not been clarified. In this study, we established a model of PCOS in the offspringrats by high androgen exposure during late pregnancy in parental and established a female rat macrophageeliminating model by rejection of clodronate liposome. Then, the offspring rat macrophage phenotype in offspringfemale rat adipose tissue, and levels of testosterone, angiogenic factors (PDGF and VEGF) and inflammatory factors(TNF-α and MCP-1) were investigated. By coculture of RAW264.7 macrophage with adipocytes or C166 endothelialcells (ECs), the mobility of adipocytes, and the ECs function with associated signalling pathway were detected byusing of androgen inhibitor Apalutamide, NF-κB inhibitor JSH-23 and ERK1/2 inhibitor LY3214996. It was foundthat 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 ofTNF-α and MCP-1 in female rats in the offspring. Eliminating macrophages significantly increased adipocytes andangiogenesis in offspring of rats with intrauterine high androgen, and reduced TNF-α and MCP-1. Macrophagespromoted mobility of adipocytes, and inhibited proliferation, migration, tube formation of ECs underhyperandrogenic condition, which were significantly inhibited by Apalutamide, JSH-23 and LY3214996. Thus,intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome throughincreasing M1 differentiation of pro-inflammatory macrophages and activating VEGF-related angiogenesis viaandrogen/NF-κB/ERK1/2 signalling pathway.

【 授权许可】

CC BY