Maternal obesity may disrupt offspring metabolism by inducing oocyte genome hyper-methylation via increased DNMTs

Maternal obesity has deleterious effects on oocyte genome methylation establishment, yet the underlying mechanisms remain unclear. In the present study, we first find that maternal obesity induced by high-fat diet (HFD) disturbs genomic methylation in oocytes, and at least a part of the altered methylation is transmitted to F2 oocytes and livers via females. We further identified that altered metabolites such as methionine and melatonin may play a key role in the re-methylation establishment in oocytes of obese mice. Exogenous melatonin treatment significantly reduces the hyper-methylation of HFD oocytes. The higher expression of DNMT3a and DNMT1 in HFD oocytes is also decreased by melatonin supplement, which may be mediated by cAMP/PKA/CREB pathway. These results suggest that maternal obesity-induced genomic methylation alterations in oocytes, can be partly transmitted to F2 in females, and that melatonin is involved in regulating the hyper-methylation of HFD oocytes via increasing the expression of DNMTs mediated by cAMP/PKA/CREB pathway.