卵子母源效应在肥胖诱发出生缺陷过程中的作用

项目名称： 卵子母源效应在肥胖诱发出生缺陷过程中的作用

项目编号： No.31301181

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 王强

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 肥胖已成为备受中国社会关注的重大公共健康问题。流行病学调查表明，肥胖会导致女性不孕不育、胎儿发育迟缓以及先天畸形等生殖问题。到目前为止，人们对于母源肥胖引起后代出生缺陷及跨代影响机理尚不明确。我们的工作基础表明，卵母细胞质量受损是母源肥胖诱发相关生殖问题的一个关键因素。而且，这种卵母细胞效应直到胚胎发育晚期才有所表现，提示表观机制可能介导了该过程。印记基因在控制胎儿生长、胎盘发育和大脑功能形成等方面发挥着重要作用。因此，我们推测，肥胖代谢环境改变了卵母细胞内相关mRNA/蛋白的表达水平，然后经由母源效应干扰了胚胎发生过程中印记基因的甲基化状态，并最终导致胎儿生长迟缓及发育异常。本研究将以高脂食物诱导和遗传肥胖小鼠为模型，应用遗传学、分子生物学和细胞生物学等学科交叉手段,拟对上述设想予以验证，以揭示卵母细胞的母源效应在肥胖对生殖结果影响过程中的介导作用,为预防出生缺陷提供理论基础和分子靶标。

中文关键词： 卵子质量；母源肥胖；出生缺陷；表观遗传；

英文摘要： Obesity is becoming a major public health problem in China. Women with poorly controlled obesity often suffered from infertility, pregnancy loss, fetal growth retardation and congenital malformations. However, so far, the mechanism by which maternal obesity causes birth defects and induces transgenerational effects remains unclear. Our preliminary data suggests that impaired oocyte quality is a critical origin of reproductive problems induced by obesity. Furthermore, such oocyte specific-maternal effects are manifested at the late stage of embryonic development, indicating the involvement of epigenetic regulation. Imprinting genes have been shown to play crucial roles in controlling fetus growth, placenta development and brain function. We therefore propose that mRNA/protein expression is altered in oocytes exposed to obesity environment, and such maternal effects further disrupt the methylation status of imprinting gene during embryogenesis, contributing to the fetus growth retardation and malformation. Here by using HFD and genetic obese mouse model, we will perform molecular, cellular and biochemical analysis to test the above hypothesis and uncover the role of oocyte specific-maternal effects in obesity induced-birth defects.

英文关键词： Oocyte quality；Maternal obesity；Birth defect；Epigenetics；