Molecular Background of Toxic-Substances-Induced Morphological Alterations in the Umbilical Cord Vessels and Fetal Red Blood Cells

The relationship between smoking and human health has been investigated mostly in adults, despite the fact that the chemicals originating from sustained maternal smoking disrupt the carefully orchestrated regulatory cascades in the developing fetus. In this study, we followed molecular alterations in the umbilical cord (UC) vessels and fetal red blood cells (RBCs), which faithfully reflect the in vivo status of the fetus. We showed evidence for the decreased level of DNA-PKcs-positive nuclei in samples with smoking origin, which is associated with the impaired DNA repair system. Furthermore, we pointed out the altered ratio of MMP-9 metalloproteinase and its endogenous inhibitor TIMP-1, which might be a possible explanation for the morphological abnormalities in the UC vessels. The presented in vivo dataset emphasizes the higher vulnerability of the veins, as the primary target for the toxic materials unfiltered by the placenta. All these events become amplified by the functionally impaired fetal RBC population via a crosstalk mechanism between the vessel endothelium and the circulating RBCs. In our ex vivo approach, we looked for the molecular explanation of metal-exposure-induced alterations, where expressions of the selected genes were upregulated in the control group, while samples with smoking origin showed a lack of response, indicative of prior long-term in utero exposure

Elevated levels of macromolecular damage are correlated with increased nitric oxide synthase expression in erythrocytes isolated from twin neonates

Pregnancy is a state associated with an enhanced metabolism and demand for O2 , which may lead to the overproduction of reactive oxygen species (ROS) and hence to oxidative stress. An elevated ROS level may result in delayed development and a low birth weight. The aim of this study was to reveal the consequences of multiple pregnancies on the redox status of neonatal human red blood cells (RBCs) and evaluate the role of endothelial nitric oxide synthase (NOS3) - expressing RBCs in the generation of oxidative stress. The study presents evidence of higher levels of production of hydrogen peroxide, peroxynitrite and nitrate content in the RBCs of twin neonates, clearly reflected by an elevated level of protein and lipid damages. This phenotype appears to be a consequence of multiple pregnancies, regardless of the level of maturity or the birth weight of the twins. Besides the higher level of ROS, there was a general decrease in the expression of genes coding for antioxidants. The first data are presented on NOS3-expressing neonatal human RBCs. The number of RBCs producing NOS3 was more than twice as high in twin neonates compared to singletons, with no correlation to maturity