Nicotinamide Riboside Mitigates Antiphospholipid Antibody-Induced Dysfunction in Human Trophoblast Cells

Obstetric antiphospholipid syndrome (APS) is characterized by the presence of circulating anti-phospholipid antibodies (aPL), which disrupt early placentation and contribute to adverse pregnancy outcomes including pregnancy loss and preterm birth. aPL, specifically those targeting beta 2 glycoprotein 1 (β₂GPI), interact with placental trophoblast cells and induce inflammation, disrupt angiogenic factor production, and reduce cell migration. In addition, aPL have been shown to promote a state of oxidative stress in trophoblast cells and in APS patients. This study aimed to investigate if the antioxidant, nicotinamide riboside (NR), could mitigate the negative effects of aPL on trophoblast cells.

The human first-trimester trophoblast cell line, Sw.71, was treated with or without aPL in the presence or absence of NR. Trophoblast supernatants were measured by ELISA for pro-inflammatory cytokines/chemokines and angiogenic factors. Cell migration was measured using a two-chamber colorimetric assay. ROS production was measured using a fluorescence assay.

NR blocked aPL-induced trophoblast inflammation and ROS production, and reversed the effects of aPL on trophoblast angiogenic factor production. However, NR was unable to rescue aPL-induced trophoblast migratory dysfunction.

NR mitigated some, but not all, aPL-induced trophoblast dysfunction. This provides new insight into the role of antioxidant therapies on aPL-induced pregnancy complications, and a possible new avenue of managing obstetric APS to explore further.