| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
EBioMedicine, Vol 16, Iss C, Pp 275-283 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2017.01.011 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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