DNA Methylation in Oocytes and Liver of Female Mice and Their Offspring: Effects of High-Fat-Diet-Induced Obesity

BACKGROUND: Maternal obesity has adverse effects on oocyte quality, embryo development, and the health of the offspring. OBJECTIVES: To understand the underlying mechanisms responsible for the negative effects of maternal obesity, we investigated the DNA methylation status of several imprinted genes and metabolism- related genes. METHODS: Using a high-fat-diet (HFD)-induced mouse model of obesity, we analyzed the DNA methylation of several imprinted genes and metabolism-related genes in oocytes from control and obese dams and in oocytes and liver from their offspring. Analysis was performed using combined bisulfite restriction analysis (COBRA) and bisulfite sequencing. RESULTS: 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. In oocytes of obese mice, the DNA methylation level of the leptin (Lep) promoter was significantly increased and that of the Ppar-alpha promoter was reduced. Increased methylation of Lep and decreased methylation of Ppar-a was also observed in the liver of female offspring from dams fed the high-fat diet (OHFD). mRNA expression of Lep and Ppar-a was also significantly altered in the liver of these OHFD. In OHFD oocytes, the DNA methylation level of Ppar-a promoter was increased. CONCLUSIONS: Our results indicate that DNA methylation patterns of several metabolismrelated genes are changed not only in oocytes of obese mice but also in oocytes and liver of their offspring. These data may contribute to the understanding of adverse effects of maternal obesity on reproduction and health of the offspring.