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PPE can lead to chondrodysplasia and increase susceptibility to adult OA in female offspring. Intrauterine Pred (rather than prednisone) exposure activated glucocorticoid receptor (GR) and recruited DNMT3B, resulting in DNA hypermethylation in the PGC-1α promoter region, thereby downregulating its expression, in articular cartilage. This leads to impaired mitochondrial biogenesis and decreased glutamine metabolic flux, the latter further leads to the downregulation of histone acetylation levels and expression of cartilage marker genes. Furthermore, intrauterine Pred exposure also increased oxidative stress, ultimately resulting in impairments in cartilage ECM synthesis.
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