Adverse effects of gestational diabetes mellitus on fetal monocytes revealed by single-cell RNA sequencing

Gestational diabetes mellitus (GDM), the most prevalent metabolic disorder during pregnancy, has long-term risks of metabolic diseases in offspring. However, the underlying mechanisms remain unclear. Here, we analyzed single-cell transcriptional data of cord blood mononuclear cells (CBMCs) from fetuses of healthy and GDM mothers, peripheral blood mononuclear cells from children and adolescents, and coronary plaques myeloid cells from atherosclerosis. Our results demonstrated that monocytes in cord blood were characterized with down-regulated proinflammatory-related pathways and up-regulated proliferation-related pathways. And monocytes in cord blood from GDM mothers were featured with expanded CXCL8+IL1B+ subclusters, enhanced crosstalk with neutrophil granulocytes and augmented adhesive and phagocytic abilities. Interestingly, CXCL8+IL1B+ monocytes influenced by GDM had transcriptome similarity with those of coronary plaques myeloid cells from individuals with atherosclerotic cardiovascular disease. Collectively, our data reveal adverse impact of maternal GDM environment on fetal monocytes and propose potential mechanisms between maternal GDM and offspring atherosclerosis.