Here, we demonstrated an early Jph2 promoter hypermethylation in VO-exposed hearts, which occurs before functional deterioration and is associated with downregulated cardiac Jph2 expression, suggesting a plausible role for hypermethylated Jph2 promoter in the progression of pathological remodeling and transition to HF upon VO exposure. The gene discussed is JPH2; the disease is hydrops fetalis.