Reproduction Abstracts

Introduction: Obesity and diabetes have adverse effects on germ cell quality, embryo development, fertility, and the health of offspring. However, the underlying mechanisms responsible for the negative effects of obesity and diabetes are little known.

Materials and methods: A high-fat-diet (HFD)-induced maternal obese mouse model, streptozotocin (STZ)-induced and nonobese diabetic (NOD) maternal diabetic mouse models, and HFD combined with STZ-induced paternal prediabetic mouse model were employed. We investigated the DNA methylation status of imprinted genes and/or metabolism-related genes in germ cells and offspring by using combined bisulfite restriction analysis and bisulfite sequencing, as well as MeDIP-Seq analysis.

Results and discussion: DNA methylation of imprinted genes in oocytes was not altered in either obese dams or their offspring; however, DNA methylation of metabolism-related genes was changed not only in oocytes of obese mice but also in oocytes and liver of their offspring. The methylation pattern of maternall imprinted gene Peg3 differential methylation regions (DMR) was affected in a time-dependent manner, and evident demethylation was observed on day 35 after STZ injection. In NOD mice, the methylation pattern of Peg3 was similar to that of STZ-induced mice. Embryo development was adversely affected by maternal diabetes; however, no evident imprinting abnormality was observed in oocytes from female offspring derived from a diabetic mother. Offspring of prediabetic fathers exhibited altered gene expression patterns in the pancreatic islets, with down-regulation of several genes involved in glucose metabolism and insulin signaling pathways. Paternal prediabetes altered overall methylome patterns in sperm, with a large portion of differentially methylated genes overlapping with that of pancreatic islets in offspring. Our data may contribute to the understanding of adverse effects of obesity and diabetes on reproduction and health of the offspring.