Effects of obesity and diabetes on the epigenetic modification of mammalian gametes.

Obesity and diabetes are closely associated with numerous reproductive disorders, including termination of ovulation, irregular menstruation, low fertility, abortion, and risky pregnancy, which are now regarded as global health problems. Paternal/maternal obesity and diabetes can also be transmitted to the subsequent generation via gametes, suggesting the association of epigenetic inheritance with obesity and diabetes, particularly for its effects on offspring. Recent studies indicate that both obesity and diabetes change DNA and histone methylation levels, histone acetylation, and noncoding RNAs such as microRNAs (miRNAs) in oocytes and sperm. Several important genes, such as PPAR-α, Igf2, H19, Fyn, Stella, Sirt3, Sirt6, and Peg3 as well as miRNAs, such as let-7c, reportedly participate in the regulation of epigenetic modifications in mammalian gametes. This review summarizes the recent progress that links obesity/diabetes and reproductive disorders from the perspective of gamete epigenetic modifications.