Assuming an intimate crosstalk between the vascular endothelium and the circulating RBCs, any endothelial dysfunction altering NO production/bioavailability can be sensed by fetal RBCs acting as a biosensor; however, in the RBC-S population, the NOS3-NO production is most likely unavailable as a compensatory mechanism to improve the blood flow to the fetus. Here, NOS3 is linked to endothelial dysfunction.