Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism

作者：Shen Tian, Xianhua Lin, Yimeng Xiong, Miao-E. Liu, Tian-tian Yu, M. Lv, Wei Zhao, Gu-feng Xu, G. Ding, Chenming Xu, M. Jin, Chun Feng, Yan-ting Wu, Ya-jing Tan, Qian Gao, Jian Zhang, Cheng Li, Jun Ren, Luyang Jin, Bin Chen, Hong Zhu, Xue-Ying Zhang, Song-chang Chen, Xin-Mei Liu, Ye Liu, Jun-Yu Zhang, Li Wang, Ping Zhang, Xiao-Jun Chen, Li Jin, Xi Chen, Yicong Meng, Dan‐dan Wu, Hui Lin, Qian Yang, Cheng-liang Zhou, Xinzhu Li, Yiyao Wang, Yuqian Xiang, Zhi-wei Liu, Ling Gao, Luting Chen, Hong-Jie Pan, Rong Li, Fang-hong Zhang, Lanfeng Xing, Yi-Min Zhu, C. Klausen, P. Leung, Ju-xue Li, F. Sun, J. Sheng, He-feng Huang · 发表于：EBioMedicine · 年份：2017 · DOI：10.1016/j.ebiom.2017.01.011 · 被引用次数：27 · 研究领域：Biology、Medicine

Background Excessive androgen exposure during pregnancy has been suggested to induce diabetic phenotypes in offspring in animal models. The aim of this study was to investigate whether pregestational maternal hyperandrogenism in human influenced the glucose metabolism in offspring via epigenetic memory from mother's oocyte to child's somatic cells. Methods Of 1782 reproductive-aged women detected pregestational serum androgen, 1406 were pregnant between 2005 and 2010. Of 1198 women who delivered, 1116 eligible mothers (147 with hyperandrogenism and 969 normal) were recruited. 1216 children (156 children born to mothers with hyperandrogenism and 1060 born to normal mother) were followed up their glycometabolism in mean age of 5 years. Imprinting genes of oocyte from mothers and lymphocytes from children were examined. A pregestational hyperandrogenism rat model was also established. Findings Children born to women with hyperandrogenism showed increased serum fasting glucose and insulin levels, and were more prone to prediabetes (adjusted RR: 3.98 (95%CI 1.16–13.58)). Oocytes from women with hyperandrogenism showed increased insulin-like growth factor 2 (IGF2) expression. Lymphocytes from their children also showed increased IGF2 expression and decreased IGF2 methylation. Treatment of human oocytes with dihydrotestosterone upregulated IGF2 and downregulated DNMT3a levels. In rat, pregestational hyperandrogenism induced diabetic phenotypes and impaired insulin secretion in offsp...