Comparative proteomic analysis of placental trophoblasts from normotensive and preeclamptic pregnancies in response to vitamin D

Background

Vitamin D deficiency/insufficiency is a risk factor for preeclampsia. Vitamin D is known to support placental trophoblast function, yet the cellular and molecular mechanisms underlying trophoblast responses to vitamin D remain largely unclear. This study aims to characterize the protein expression profiles, signaling pathways, and cellular networks modulated by vitamin D in trophoblasts derived from normal and preeclamptic placentas.

Study design

Fourteen placentas were included in this study—seven from normal pregnancies and seven from preeclamptic cases. Trophoblasts were isolated and cultured with or without vitamin D. Vitamin D receptor expression was assessed using Western blot analysis. A gel-based proteomic assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze protein expression profiles. Functional enrichment and pathway analysis were performed using the PANTHER database.

Results

Distinct protein expression profiles and signaling pathways were observed between trophoblasts from normal and preeclamptic placentas in response to vitamin D. In normal trophoblast cells, vitamin D upregulated proteins associated with amino acid and fatty acid metabolism, etc. In preeclamptic trophoblasts, vitamin D upregulated proteins related to cytoskeletal dynamics and ATP metabolism. Notably, vitamin D downregulated MHC class I receptor-associated proteins in both normal and preeclamptic trophoblasts.

Conclusion

Vitamin D modulates a wide range of protein expression profiles and signaling pathways in trophoblasts, impacting key biological processes such as energy production, biosynthesis, metabolism, cell motility, and respiration. Importantly, vitamin D-mediated downregulation of MHC class I receptor activity suggests a potential role of vitamin D in promoting immune tolerance at the maternal-fetal interface.