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.

在双胞胎/多胎妊娠中，兄弟姐妹经历不利的宫内环境，这是导致病理状况的主要病因。胎儿发育状态高度取决于一氧化氮 (NO) 水平，一氧化氮 (NO) 水平促进血管舒张，进而调节氧气和营养供应。由于脐带 (UC) 缺乏神经支配，内皮一氧化氮合酶 (NOS3) 的激活对于维持足够的 NO 产生至关重要。最近的突破性事实表明，在压力条件下，循环红细胞 (RBC) 可以主动产生 NO 作为“救援机制”。所以，这项研究主要关注通过改变 NOS3 激活（在 UC 动脉和静脉内皮和红细胞中）影响氧化还原环境的分子机制，这对发育参数（如出生体重）有影响。与此相关，我们追求血管内皮和循环红细胞之间的通信效率，以满足生物可利用 NO 的需求。我们的结果表明，在第 33-35 周阶段孪生本身不会降低脐带血管中的 NOS3 水平及其磷酸化状态。然而，在此期间，RBC-NOS3 激活高度上调——为胎儿红细胞在血流速率中的积极调节作用提供了额外的证据——并且这种功能活动与胎儿的出生体重高度相关。