Fetal oxygen supply can be improved by an effective cross-talk between fetal erythrocytes and vascular endothelium

In twin/multiple pregnancy, siblings experience an adverse intrauterine environment which forms the major etiological factor leading to pathological conditions. The status of the developing fetus is highly determined by the nitric oxide (NO) level, that facilitates vasodilation which in turn modulates the oxygen and nutrition supply. As the umbilical cord (UC) lacks innervation, activation of the endothelial nitric oxide synthase (NOS3) is fundamental to maintain adequate NO production. Recent ground breaking fact showed that under stress conditions, circulating red blood cells (RBCs) can actively produces NO as a "rescue mechanism". Therefore, this study majorly focused on the molecular mechanisms that affected the redox environment by altering NOS3 activation - both in the UC arteries and vein endothelium and RBCs - that have impacts on developmental parameters, like birth weight. In connection to that, we pursued the communication efficiency between the vessels' endothelium and the circulating RBCs in demand of bioavailable NO. Our results indicated that twinning itself at stage 33-35 weeks, does not reduce the NOS3 level and its phosphorylation status in the cord vessels. However, RBC-NOS3 activation is highly upregulated during this period - providing additional evidence for the active regulatory role of fetal RBCs in the rate of blood flow - and this functional activity highly correlates with the birth weight of the fetuses. Detailed analysis on NOS3 signalling at different time points of gestation could establish a benchmark in understanding of the pathophysiological mechanisms involved in the process of developing neonatal vascular diseases.