Transgenerational Glucose Intolerance With Igf2 / H19 Epigenetic Alterations in Mouse Islet Induced by Intrauterine Hyperglycemia

摘要: Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of in offspring. However, the mechanisms involved and possibilities transgenerational transmission are still unclear. We intercrossed male female adult control first-generation offspring GDM (F1-GDM) mice obtain second-generation (F2) four groups: C♂-C♀, C♂-GDM♀, GDM♂-C♀, GDM♂-GDM♀. found that birth weight significantly increased F2 through paternal line impaired glucose tolerance (IGT). Regardless from F1-GDM or without IGT, IGT appeared as early 3 weeks progressed both parental lineages, especial line. was more obvious than females, characteristics sex-specific transmission. In F1 GDM, expression imprinted genes Igf2 H19 downregulated pancreatic islets, caused by abnormal methylation status differentially methylated region, which may one for islet ultrastructure function. Furthermore, altered gene sperm F1-GDM, regardless presence indicating changes epigenetics germ cells contributed