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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Umbilical Cord* ; Placenta*; Pregnancy ; Adult ; Female ; Humans ; Fetus ; Smoking/adverse effects ; Erythrocytes/chemistry ; Fetal Blood/metabolism

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.

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GINOP-2.3.2-15-2016-00040 European Union and the Hungarian Government

Keywords: DNA double-strand break; ex vivo metal treatment; fetal red blood cells (RBCs); maternal smoking; matrix metallopeptidase-9/metallopeptidase inhibitor-1 (MMP-9/TIMP-1); umbilical cord (UC)

Date Created: 20221211 Date Completed: 20221216 Latest Revision: 20221221

20231215

PMC9736329

10.3390/ijms232314673

36499001