1,25(OH)2D3 Protects Trophoblasts Against Insulin Resistance and Inflammation Via Suppressing mTOR Signaling

Gestational diabetes mellitus (GDM) is the primary cause of maternal and fetal morbidity and mortality. Insulin resistance (IR) is pivotal to GDM pathogenesis, and mammalian target of rapamycin (mTOR) is a critical regulator of GDM. An increasing amount of evidence indicates that vitamin D deficiency is a risk factor for GDM. However, there are few reports on the effect of IR on GDM placentas. The present study aims to verify that 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃) can ameliorate trophoblast IR by suppressing mTOR signaling. An IR BeWo cell model was established in the presence of high insulin and glucose medium. The IR level and mTOR activation with or without 1,25(OH)₂D₃ treatment were evaluated. The IR cells exhibited excessive mTOR signaling activation, upregulated inflammatory factor levels, and extensive lipid infiltration. However, 1,25(OH)₂D₃ reversed mTOR activation and reduced the IR level and lipid infiltration. In addition, 1,25(OH)₂D₃ treatment in GDM placental explants blocked the aberrant, increased levels of leptin, TNF-α, and IL-6. Therefore, 1,25(OH)₂D₃ treatment protects trophoblasts against high IR mainly through suppressing mTOR signaling, and this mechanism may serve as a potential therapy for patients with GDM.