Paternal Diabetes Contributed To Metabolic Disorders In The Offspring

Aims:Paternal and maternal diabetes is one of the most important risk factors in diabetes mellitus of the offspring. Diabetes in maternal and pregnancy has been systematically researched in offspring, however, little is unknown about the effect of paternal diabetes on the metabolic disorder in offspring. A number of epidemiological studies demonstrated that paternal diabetes is more correlated to the metabolic disorder of the offspring. Therefore, the aim of this study is to investigate the influence of paternal diabetes on metabolism of the offspring.Methods:Male SD rats were intraperitoneally injected with streptozotocin (STZ,35 mg/kg), and those rats whose blood glucose ranged from 16.7 mM to 26.0 mM were selected as paternal diabetes, and then mated with healthy female SD rats. Body weight, fed and fasting blood glucose, glucose tolerance test (GTT) were determined in the offspring. Hyperinsulinemic-euglycemic clamp were performed to assess insulin sensitivity in the aged offspring. Animals were sacrificed, serum and liver were collected. HE staining, oil-red O staining, transmission electron microscopy, analysis of triglycerides content, gene methylation was operated in liver tissue.Results:Blood glucose levels in STZ-treated male rats (DM) were significantly higher than the control male rats (CT). Body weight in offspring of paternal diabetic rats(DM-O) was significantly higher than in the offspring of control rats (CT-O). Fasting and fed blood glucose was similar between two groups. GTT showed that glucose tolerance was impaired in the DM-O rats. Hyperinsulinemic-euglycemic clamp test showed that the glucose infusion rate was significantly lower in aging DM-O than that in the CT-O. Additionally, ALT and AST were similar in two groups, TC, TG and LDL were significantly higher in DM-O than those in CT-O, HDL was significantly lower in DM-0 than that in CT-O. HE and Oil red O staining revealed that liver tissues lipidosis was more serious in DM-O than that in CT-O. Liver TG content was significantly increased in DM-O, compared to that in CT-O. Methylation analysis of gene showed that many genes methylation level markedly changed in liver tissue.Conclusion:Paternal diabetes mellitus induced metabolic disorders in the offspring, which was caused by epigenetic change in the liver.