The role of lactate metabolism in uterine spiral artery remodelling.

Lactate is a key metabolite of glycolysis. Since the proposal of the lactate shuttle hypothesis, accumulating evidence indicates that lactate is not only an essential energy substrate but also a key signalling molecule that regulates cellular functions under both physiological and pathological conditions. Uterine spiral artery (SpA) remodelling is a critical event in successful pregnancy. It involves complex interactions among trophoblasts, vascular smooth muscle cells (VSMCs), decidual immune cells, and endothelial cells (ECs). Similar to the tumour microenvironment, physiological hypoxia at the maternal-foetal interface during early pregnancy drives decidual cells, blastocysts, trophoblasts, and immune cells to undergo aerobic glycolysis, leading to local lactate accumulation and the formation of an acidic microenvironment. This review systematically elucidates the role and molecular mechanisms of lactate metabolism in SpA remodelling. It explores the association between dysregulated lactate metabolism and recurrent pregnancy loss (RPL), preeclampsia (PE), and foetal growth restriction (FGR). The findings of this review indicate that targeting lactate metabolism may represent a promising strategy for the management of pregnancy complications. Further in-depth mechanistic research and clinical obstetric research are warranted.