Many studies have shown that TGF-β1/Smad-2 and Smad-3 are major downstream regulators promoting TGF-β-mediated HF, while Smad-7 is a negative feedback regulator of the TGF-β1 signaling pathway which has a protective effect on TGF-β-mediated HF (Xu et al., 2016; Hu H. H. et al., 2018; Dewidar et al., 2019). This evidence concerns the gene SMAD2 and hydrops fetalis.