Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism
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 me...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-02-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417300154 |
| _version_ | 1818250046428151808 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shen Tian |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T15:46:10Z |
| format | Article |
| id | doaj.art-3889affc302e463f970f8c4282879a1b |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-12T15:46:10Z |
| publishDate | 2017-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-3889affc302e463f970f8c4282879a1b2022-12-22T00:19:44ZengElsevierEBioMedicine2352-39642017-02-0116C27528310.1016/j.ebiom.2017.01.011Prevalence of Prediabetes Risk in Offspring Born to Mothers with HyperandrogenismShen Tian0Xian-Hua Lin1Yi-Meng Xiong2Miao-E Liu3Tian-Tian Yu4Min Lv5Wei Zhao6Gu-Feng Xu7Guo-Lian Ding8Chen-Ming Xu9Min Jin10Chun Feng11Yan-Ting Wu12Ya-Jing Tan13Qian Gao14Jian Zhang15Cheng Li16Jun Ren17Lu-Yang Jin18Bin Chen19Hong Zhu20Xue-Ying Zhang21Song-Chang Chen22Xin-Mei Liu23Ye Liu24Jun-Yu Zhang25Li Wang26Ping Zhang27Xiao-Jun Chen28Li Jin29Xi Chen30Yi-Cong Meng31Dan-Dan Wu32Hui Lin33Qian Yang34Cheng-Liang Zhou35Xin-Zhu Li36Yi-Yu Wang37Yu-Qian Xiang38Zhi-Wei Liu39Ling Gao40Lu-Ting Chen41Hong-Jie Pan42Rong Li43Fang-Hong Zhang44Lan-Feng Xing45Yi-Min Zhu46Christian Klausen47Peter C. K Leung48Ju-Xue Li49Fei Sun50Jian-Zhong Sheng51He-Feng Huang52The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Reproductive Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Reproductive Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, CanadaDepartment of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, CanadaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaThe Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, ChinaBackground: 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.http://www.sciencedirect.com/science/article/pii/S2352396417300154HyperandrogenismOffspringPrediabetesEpigenetics |
| spellingShingle | 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 Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism EBioMedicine Hyperandrogenism Offspring Prediabetes Epigenetics |
| title | Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism |
| title_full | Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism |
| title_fullStr | Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism |
| title_full_unstemmed | Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism |
| title_short | Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism |
| title_sort | prevalence of prediabetes risk in offspring born to mothers with hyperandrogenism |
| topic | Hyperandrogenism Offspring Prediabetes Epigenetics |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417300154 |
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