Fig. 1
From: Oocyte TET3: an epigenetic modifier responsible for maternal inheritance of glucose intolerance
Oocyte TET3 mediates maternal inheritance of glucose intolerance. The mature sperm genome undergoes active demethylation after fertilization. Oocyte TET3 is responsible for demethylation of the paternal genome by catalyzing the conversion of 5mC into 5hmC and other high-oxidation products. In fertilized oocytes from healthy mice, TET3 demethylates the promoter of several genes involved in insulin secretion such as Gck, leading to normal expression of these genes and insulin secretion in the pancreas at the adult stage. In contrast, Tet3 mRNA is reduced in oocytes from hyperglycemic mice, resulting in hypermethylation of the paternal-derived Gck promoter. This leads to decreased Gck expression and lower levels of insulin secretion in the pancreatic islets of the offspring in adulthood. Furthermore, injection of exogenous Tet3 mRNA in oocytes from hyperglycemic mice could rescue impaired insulin secretion, and thus glucose intolerance in offspring
