The overview of lactylation in the placenta of preeclampsia

Preeclampsia is a major challenge for obstetricians due to its severe impacts on maternal and fetal health. Lysine lactylation (Kla) derived from lactate is a novel type of post-translational modification which has been confirmed to affect the malignant progression of diseases as an epigenetic modifier. However, the systemic lactylome profiling of preeclampsia is still unclear.

Immunohistochemistry and protein immunoassay were performed on placenta tissues from preeclamptic patients and control pregnancies to compare lactylation levels between the groups. Then liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized for quantitative lactylomic analysis and proteomic assessment for proteins with differentially lactated modification. Bioinformatics analyses were applied to reveal the conserved motif sequences and enrichment pathways.

Significant differences in protein lactylation levels were evident in the placenta between preeclamptic and control groups, with modifications observed in both histone and non-histone proteins. Lactylome analysis showed significant downregulation of 59 Kla proteins and 69 Kla sites in preeclamptic placentas, whereas 44 proteins and 60 sites were upregulated. These differentially lactylated proteins were primarily mitochondrial and associated with the citrate cycle (TCA cycle). Enriched metabolic pathways linked to lactylation included those important for vascular muscle contraction, platelet activation, and several signaling pathways like PI3K-Akt, PPAR, and cholesterol metabolism.

Preeclamptic placentas exhibit distinct lactylation profiles compared to normal pregnancies, primarily affecting mitochondrial and TCA cycle-related energy metabolism. These changes contribute to the pathophysiology of preeclampsia by involving metabolic pathways critical for angiogenesis and endothelial function.