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首页> 外文期刊>EBioMedicine >Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism
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Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism

机译：高雄激素症母亲的后代患糖尿病前风险的普遍性

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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.
机译：背景：在动物模型中，怀孕期间过度暴露雄激素已被认为可诱发后代糖尿病表型。这项研究的目的是研究人的孕前母体高雄激素是否通过从母亲卵母细胞到孩子体细胞的表观遗传记忆影响后代的葡萄糖代谢。方法：2005年至2010年间，在1782名检测到孕前血清雄激素的育龄妇女中，有1406人怀孕。在分娩的1198名妇女中，招募了1116名合格的母亲（147名高雄激素血症和969名正常）。对1216名儿童（156名患有高雄激素血症的母亲所生，1060名正常母亲的孩子）进行了糖代谢试验，平均年龄为5岁。检查了母亲的卵母细胞和儿童淋巴细胞的印迹基因。还建立了妊娠高雄激素血症大鼠模型。研究结果：高雄激素血症女性所生的孩子表现出血清空腹血糖和胰岛素水平升高，并且更容易发生糖尿病前期（经调整的RR：3.98（95％CI 1.16-13.58））。高雄激素血症女性的卵母细胞显示胰岛素样生长因子2（IGF2）表达增加。他们孩子的淋巴细胞还显示出IGF2表达增加和IGF2甲基化降低。用二氢睾丸激素治疗人卵母细胞可上调IGF2和下调DNMT3a水平。在大鼠中，孕前雄激素过多症会诱发糖尿病表型，并且后代的胰岛素分泌受损。与人类的发现一致，高雄激素血症也增加了大鼠卵母细胞中Igf2的表达并降低了DNMT3a。重要的是，在后代胰岛中鉴定出相同的Igf2甲基化标记改变。解释：妊娠高雄激素血症可能是通过表观遗传的卵母细胞遗传使后代易患葡萄糖代谢异常。临床试验注册号：ChiCTR-OCC-14004537; www.chictr.org。

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