糖尿病影响小鼠卵母细胞组蛋白乙酰化的机制

糖尿病低龄化现象日趋严重，对生殖健康造成诸多不利影响，甚至导致大量不良妊娠结局，这些都与卵母细胞质量降低有关，但至今关于糖尿病影响卵母细胞质量的机制仍未阐明。我们用STZ诱导的糖尿病模型小鼠进行了前期实验，结果表明：糖尿病小鼠卵母细胞减数分裂成熟过程中组蛋白H3、H4的六个赖氨酸位点的去/乙酰化水平显著升高，组蛋白乙酰化转移酶（HAT）和组蛋白去乙酰化酶（HDAC）的表达异常。本项目将以Ins2基因突变和STZ诱导的糖尿病小鼠为实验模型，①找出糖尿病引起小鼠卵母细胞组蛋白乙酰化的异常规律；②探索晚期糖基化终末产物（AGEs）对小鼠卵母细胞组蛋白乙酰化异常的影响及最终导致卵母细胞质量降低的机制。实现从源头上揭示糖尿病影响卵母细胞质量的原因，以期为解决糖尿病患者的生殖问题提供较好的理论依据和实践基础。

Diabetes is becoming more and more serious and emerge a younger age trend. It causes many adverse effects on reproductive health and even leads to adverse pregnancy outcomes. This may be related to the low oocyte quality. However, how diabetes affects oocyte quality remains unclear. In our preliminary experiments, STZ-induced diabetic mice were used as the research model. The result shows that the acetylation/deacetylation level of six histone H3 and H4 core lysine sites was increased significantly in diabetic mouse oocyte and histone acetylase and histone deacetylase system exhibits expression disorder. In this program, we will further employ Ins2 gene mutation and STZ-induced diabetic mice as the experiment model to ① identify how diabetes would cause abnormal histone acetylation in mouse oocytes. ② explore the effect of advanced glycation end products (AGEs) on histone acetylation and how it ultimately lead to poor oocyte quality. Our study will find out how diabetes affects mouse oocyte quality and this may provide a good theoretical and practical basis to solve problems of diabetes.