Whole transcriptome analysis of the effects of type I diabetes on mouse oocytes.

Abstract

In mouse ovarian follicles, granulosa cells but not oocytes take up glucose to provide the oocyte with nourishments for energy metabolism. Diabetes-induced hyperglycemia or glucose absorption inefficiency consistently causes granulosa cell apoptosis and further exerts a series of negative impacts on oocytes including reduced meiosis resumption rate, low oocyte quality and preimplantation embryo degeneration. Here we compared the transcriptome of mouse oocytes from genetically derived NOD diabetic mice or chemically induced STZ diabetic mice with that of corresponding normal mice. Differentially expressed genes were extracted from the two diabetic models. Gene set enrichment analysis showed that genes associated with metabolic and developmental processes were differentially expressed in oocytes from both models of diabetes. In addition, NOD diabetes also affected the expression of genes associated with ovulation, cell cycle progression, and preimplantation embryo development. Notably, Dnmt1 expression was significantly down-regulated, but Mbd3 expression was up-regulated in diabetic mouse oocytes. Our data not only revealed the mechanisms by which diabetes affects oocyte quality and preimplantation embryo development, but also linked epigenetic hereditary factors with metabolic disorders in germ cells.