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Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism.
Tian, Shen; Lin, Xian-Hua; Xiong, Yi-Meng; Liu, Miao-E; Yu, Tian-Tian; Lv, Min; Zhao, Wei; Xu, Gu-Feng; Ding, Guo-Lian; Xu, Chen-Ming; Jin, Min; Feng, Chun; Wu, Yan-Ting; Tan, Ya-Jing; Gao, Qian; Zhang, Jian; Li, Cheng; Ren, Jun; Jin, Lu-Yang; Chen, Bin; Zhu, Hong; Zhang, Xue-Ying; Chen, Song-Chang; Liu, Xin-Mei; Liu, Ye; Zhang, Jun-Yu; Wang, Li; Zhang, Ping; Chen, Xiao-Jun; Jin, Li; Chen, Xi; Meng, Yi-Cong; Wu, Dan-Dan; Lin, Hui; Yang, Qian; Zhou, Cheng-Liang; Li, Xin-Zhu; Wang, Yi-Yu; Xiang, Yu-Qian; Liu, Zhi-Wei; Gao, Ling; Chen, Lu-Ting; Pan, Hong-Jie; Li, Rong; Zhang, Fang-Hong; Xing, Lan-Feng; Zhu, Yi-Min; Klausen, Christian; Leung, Peter C K; Li, Ju-Xue.
Afiliación
  • Tian S; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China; Department of Reproductive Medicine, The Second Affiliated Hospital, Sc
  • Lin XH; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Xiong YM; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Liu ME; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Yu TT; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Lv M; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Zhao W; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Xu GF; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Ding GL; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Xu CM; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Jin M; Department of Reproductive Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Feng C; Department of Reproductive Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Wu YT; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Tan YJ; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Gao Q; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China.
  • Zhang J; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Li C; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Ren J; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
  • Jin LY; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
  • Chen B; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Zhu H; The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, 310006, China; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Zhang XY; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Chen SC; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Liu XM; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Liu Y; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Zhang JY; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Wang L; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Zhang P; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Chen XJ; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Jin L; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Chen X; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Meng YC; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Wu DD; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Lin H; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Yang Q; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Zhou CL; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Li XZ; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Wang YY; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Xiang YQ; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Liu ZW; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Gao L; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Chen LT; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Pan HJ; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Li R; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
  • Zhang FH; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Xing LF; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Zhu YM; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
  • Klausen C; Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
  • Leung PCK; Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
  • Li JX; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200
EBioMedicine ; 16: 275-283, 2017 Feb.
Article en En | MEDLINE | ID: mdl-28111236
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 5years. 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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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Estado Prediabético / Hiperandrogenismo / Epigénesis Genética / Madres Tipo de estudio: Etiology_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Animals / Child / Child, preschool / Female / Humans / Male / Pregnancy País/Región como asunto: Asia Idioma: En Revista: EBioMedicine Año: 2017 Tipo del documento: Article País de afiliación: Seychelles
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Estado Prediabético / Hiperandrogenismo / Epigénesis Genética / Madres Tipo de estudio: Etiology_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Animals / Child / Child, preschool / Female / Humans / Male / Pregnancy País/Región como asunto: Asia Idioma: En Revista: EBioMedicine Año: 2017 Tipo del documento: Article País de afiliación: Seychelles