Placental dysfunction influences fetal monocyte subpopulation gene expression in preterm birth

Purpose: Identify differences in gene expression profiles in fetal monocytes - cells that persist and differentiate postnatally - according to distinct placental histologic domains. Methods: We first isolated classical and intermediate monocyte subsets via FACS and performed transcriptomic profiling of 140 samples (70 classical and 70 intermediate monocyte samples) using bulk RNA-Seq. Results: We report that placental lesions are associated with gene expression changes in fetal monocyte subsets. Specifically,fetal monocytes exposed to acute placental inflammation upregulate biological processes related to monocyte activation, monocyte chemotaxis, and platelet function while monocytes exposed to maternal vascular malperfusion lesions downregulate these processes. Additionally, we show that intermediate monocytes might be a source of mitogens, such as HBEGF, NRG1, and VEGFA, implicated in different outcomes related to prematurity. Conclusions: This is the first study to show that placental lesions are associated with unique changes in fetal monocytes and monocyte subsets. As fetal monocytes persist and differentiate into various phagocytic cells following birth, our study may provide insight into morbidity related to prematurity and ultimately potential therapeutic targets. Overall design: Gene expression profiles of sorted fetal monoctyes.