Glucocorticoid exposure induces preeclampsia via dampening 1,25-dihydroxyvitamin D₃

The pathogenesis of preeclampsia (PE) involves a number of biological processes that may be directly or indirectly affected by glucocorticoid (GC) and vitamin D. GC exposure increases the risk of PE, and 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) deficiency may result in PE. The purpose of the present study was to confirm the involvement of GC/1,25-(OH)₂D₃ axis in the pathogenesis of PE. In the study, cortisol levels of PE patients were found to be higher than that of non-complicated pregnancies, while 1,25-(OH)₂D₃ were decreased in both PE women and GC-induced PE rats. Mechanically, GC reduced 1,25-(OH)₂D₃ levels via disturbing its biosynthetic and catabolic enzymes, including Cyp3a1,Cyp24a1 and Cyp27b1, especially enhancing the expressions of Cyp3a1, the dominant enzyme for vitamin D degeneration. Moreover, replenishing 1,25-(OH)₂D₃ ameliorated the symptoms and placental oxidative stress of GC-induced rat PE. The protective actions of 1,25-(OH)₂D₃ might be explained by its roles in antagonizing the effects of GC on trophoblast proliferation and apoptosis. Together, these findings suggest that GC exposure could lead to PE via dampening 1,25-(OH)₂D₃ biosynthesis, and GC/1,25-(OH)₂D₃ axis might represent a common pathway through which PE occurs.