Multi-organ transcriptomic atlas reveals hallmarks of labor

Pregnancy and labor are dynamic processes involving various rapid biological changes. Previous studies found that during pregnancy there are gradual alterations in immune and metabolic pathways. In contrast, changes linked to labor are less well-known, generally limited to reports on specific differentially expressed genes, lacking a more comprehensive overview of changes of the overall signalling landscapes. Moreover, most previous works were standalone, based on individual organs. Here, we aimed to present a more systematic and holistic overview of the impacts of labor on both the maternal and fetal aspects. For this purpose, we collated a multi-organ transcriptomic atlas to decipher the influences of labor on multiple maternal and fetal compartments, covering the maternal adipose tissues (subcutaneous and visceral fat), peripheral blood, myometrium and placenta and fetal cord blood mononuclear cells (CBMCs), and spanning both physiological and pathological conditions. During labor, activation of pro-inflammatory TNF signaling was found in all maternal compartments except adipose tissues, which, along with myometrium, showed upregulation in glycolysis. Myc signaling, as a critical nexus within the intracellular signaling network, was generally enhanced in labor. Contrarily, fetal CBMCs in labor upregulated the anti-inflammatory TGF{beta} pathway. Importantly, changes in the maternal TNF signaling were conserved across the spectrum of healthy pregnancy of different parities, and pathological conditions like preterm pregnancy and smoking-affected pregnancy. Mechanistically, it might be explained by the reduction in progestin hormonal signals during labor but not by the mechanical stress. Collectively, we present a comprehensive multi-organ transcriptomic atlas elucidating the maternal and fetal immune and metabolic landscapes associated with labor, shedding light on the complex physiology.