EBioMedicine (Feb 2017)
Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism
- Shen Tian,
- Xian-Hua Lin,
- Yi-Meng Xiong,
- Miao-E Liu,
- Tian-Tian Yu,
- Min Lv,
- Wei Zhao,
- Gu-Feng Xu,
- Guo-Lian Ding,
- Chen-Ming Xu,
- Min Jin,
- Chun Feng,
- Yan-Ting Wu,
- Ya-Jing Tan,
- Qian Gao,
- Jian Zhang,
- Cheng Li,
- Jun Ren,
- Lu-Yang 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,
- Yi-Cong Meng,
- Dan-Dan Wu,
- Hui Lin,
- Qian Yang,
- Cheng-Liang Zhou,
- Xin-Zhu Li,
- Yi-Yu Wang,
- Yu-Qian Xiang,
- Zhi-Wei Liu,
- Ling Gao,
- Lu-Ting Chen,
- Hong-Jie Pan,
- Rong Li,
- Fang-Hong Zhang,
- Lan-Feng Xing,
- Yi-Min Zhu,
- Christian Klausen,
- Peter C. K Leung,
- Ju-Xue Li,
- Fei Sun,
- Jian-Zhong Sheng,
- He-Feng Huang
Affiliations
- Shen Tian
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Xian-Hua Lin
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Yi-Meng Xiong
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Miao-E Liu
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Tian-Tian Yu
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Min Lv
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Wei Zhao
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Gu-Feng Xu
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Guo-Lian Ding
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Chen-Ming Xu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Min Jin
- Department of Reproductive Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Chun Feng
- Department of Reproductive Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Yan-Ting Wu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Ya-Jing Tan
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Qian Gao
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Jian Zhang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Cheng Li
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Jun Ren
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Lu-Yang Jin
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Bin Chen
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Hong Zhu
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- Xue-Ying Zhang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Song-Chang Chen
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Xin-Mei Liu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Ye Liu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Jun-Yu Zhang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Li Wang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Ping Zhang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Xiao-Jun Chen
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Li Jin
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Xi Chen
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Yi-Cong Meng
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Dan-Dan Wu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Hui Lin
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Qian Yang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Cheng-Liang Zhou
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Xin-Zhu Li
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Yi-Yu Wang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Yu-Qian Xiang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Zhi-Wei Liu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Ling Gao
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Lu-Ting Chen
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Hong-Jie Pan
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Rong Li
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Fang-Hong Zhang
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Lan-Feng Xing
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Yi-Min Zhu
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
- Christian Klausen
- Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
- Peter C. K Leung
- Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
- Ju-Xue Li
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Fei Sun
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
- Jian-Zhong Sheng
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- He-Feng Huang
- The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China
- DOI
- https://doi.org/10.1016/j.ebiom.2017.01.011
- Journal volume & issue
-
Vol. 16,
no. C
pp. 275 – 283
Abstract
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 offspring. In consistent with the findings in human, hyperandrogenism also increased Igf2 expression and decreased DNMT3a in rat oocytes. Importantly, the same altered methylation signatures of Igf2 were identified in the offspring pancreatic islets. Interpretation: Pregestational hyperandrogenism may predispose offspring to glucose metabolism disorder via epigenetic oocyte inheritance. Clinical trial registry no.: ChiCTR-OCC-14004537; www.chictr.org.
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