The present study has provided evidence showing that female germline methylation changes may mediate the transgenerational inheritance of the perturbed metabolism; the DNA methylation changes in F1 oocytes induced by malnutrition in utero may mediate, at least partly, the abnormal expression of metabolism-related genes, causing dysfunction of insulin and metabolic disorders of F2 offspring (Additional file 1: Fig. S8). Here, INS is linked to metabolic disease.