Elevated galectin-3 levels detected in women with hyperglycemia during early and mid-pregnancy antagonizes high glucose − induced trophoblast cells apoptosis via galectin-3/foxc1 pathway

OBJECTIVE: This study was to evaluate plasma galectin-3 levels from early pregnancy to delivery and explore the effects of galectin-3 on the function of trophoblast cells under high glucose exposure. METHODS: The plasma galectin-3 levels were quantified by enzyme-linked immunosorbent assay (ELISA) in the China National Birth Cohort (CNBC) at Peking University First Hospital, and the underlying signaling pathway was identified by protein–protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), quantitative PCR (qPCR), western blotting, small interfering RNA (siRNA) transfections, and flow cytometry. RESULTS: Significantly higher galectin-3 levels were found in patients with gestational diabetes mellitus (GDM group; n = 77) during the first and second trimesters than that in healthy pregnant women (HP group; n = 113) (P < 0.05). No significant differences in plasma galectin-3 levels were detected between GDM and HP groups in maternal third-trimester blood and cord blood. PPI analysis suggested potential interactions between galectin-3 and foxc1. The findings of GSEA showed that galectin-3 was involved in the cytochrome P450-related and complement-related pathways, and foxc1 was associated with type I diabetes mellitus. Additionally, high glucose (25 mM) significantly increased the expression levels of galectin-3 and foxc1 and induced apoptosis in HTR-8/SVneo cells. Further in vitro experiments showed that galectin-3/foxc1 pathway could protect HTR-8/SVneo cells against high glucose − induced apoptosis. CONCLUSION: Future studies were required to validate whether plasma galectin-3 might become a potential biomarker for hyperglycemia during pregnancy. Elevated galectin-3 levels might be a vital protective mechanism among those exposed to hyperglycemia during pregnancy. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-023-00707-5.