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

Abstract

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.

Stress-Induced Changes in Nucleocytoplasmic Localization of Crucial Factors in Gene Expression Regulation

“…In addition to the UC vascular system, the circulating fetal red blood cells (RBCs) are also directly affected by the unfiltered toxic materials and become a source of reactive oxygen and nitrogen species [6]. As we hypothesized and proved in our latest publications, there is an active communication between the vessel endothelial cells and RBC population; thus, changes in the structure and molecular network of any affect the functionality of the other [7,8].…”

“…Veins were always affected to a greater extent, probably due to their primary exposition to toxic materials, unfiltered by the placenta [23]. Along with the morphological changes, altered gene expression profiles were also detected with significant correlation to damage of red blood cell populations [8].…”