The Protective Effect of Vitamin D Against Necroptosis in Preeclampsia

OBJECTIVE: Preeclampsia is correlated with an inflammatory condition. Necroptosis is a programmed cell death with an inflammatory state. Vitamin D has anti-inflammatory properties; however, there has been no study linking vitamin D and necroptosis in preeclampsia. This study is aimed at evaluating vitamin D status and necroptosis activity in preeclampsia. METHODS: A cross-sectional study was conducted in Jakarta during 2021-2023. Subjects were grouped into normal and preeclampsia. Following delivery, venous blood and placental samples were taken. Serum and placental 25(OH)D assays were performed by LC-MS/MS. Immunohistochemistry was performed to measure necrosomes RIPK1, RIPK3, and MLKL in trophoblast and endothelial. RESULTS: A total of 60 subjects participated (31 normal and 29 preeclampsia). The preeclampsia group had lower gestational age (35 vs. 38 weeks), lower birth weight (3080.33 ± 454.62 g vs. 2283.27 ± 833.63 g), lower placental weight (580.40 ± 129.36 g vs. 453.06 ± 173.65 g), lower placental 25(OH)D (15.00 [3.50-58.00] vs. 26.50 [5.00-153.00] ng/mL, p = 0.014), and higher trophoblast RIPK3 (93.88 [23.94] vs. 76.20 [20.59], p = 0.003). A mild to moderate negative correlation between placental 25(OH)D and trophoblast RIPK3 (-0.352, p = 0.003), endothelial RIPK3 (r = -0.244, p = 0.03), and trophoblast MLKL (r = -0.296, r - 0.011) were observed. CONCLUSION: Lower placental 25(OH)D concentration is associated with an increased placental necroptosis activity in preeclampsia.