In vitro, metformin alleviated phosphate- and TGFβ-induced osteogenic differentiation of human VICs through activating the PI3K/AKT pathway and β-catenin pathway which emerged as important regulatory axis in the pathological process of CAVD (En et al., 2021; Liu et al., 2018). Here, TGFB1 is linked to congenital bilateral aplasia of vas deferens from CFTR mutation.