Placental vitamin D malnutrition induced by vitamin D deficiency during pregnancy causes placenta dysplasia by regulating GSK-3β/β-catenin and CD44 as well as interfering their feedback interaction in rats.

Vitamin D deficiency (VDD) is highly prevalent during pregnancy, which can lead to poor placental development and functional abnormalities, and may trigger a series of pregnancy-related diseases in severe cases. The Wnt/β-catenin signaling pathway and its downstream target gene, cluster of differentiation 44 (CD44), play key roles in regulating the proliferation, migration, and invasion of placental trophoblast cells. In this study, we found that VDD before and during Sprague Dawley rats' pregnancy can lead to maternal placental vitamin D malnutrition, placental dysplasia, and impaired placental invasion, migration, proliferation, and nutrient transport capabilities of placenta in vivo and in vitro. Importantly, we clarified VDD impaired placental function via regulation of phospho-glycogen synthase kinase 3 β (GSK-3β/β)-catenin and cluster of differentiation 44, and that there is a feedback regulation between phospho-glycogen synthase kinase 3 β/β-catenin and cluster of differentiation 44 in regulating VDD-induced placental dysfunction. This study once again emphasizes the importance of vitamin D for placental development and provides a theoretical basis for the prevention and treatment of placental dysplasia caused by VDD during pregnancy.