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

Author:

Zahorán SzabolcsORCID,Márton Ágnes,Dugmonits Krisztina,Chakraborty Payal,Khamit AliORCID,Hegyi Péter,Orvos Hajnalka,Hermesz Edit

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.

Funder

European Union and the Hungarian Government

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference53 articles.

1. Oxidants in Cigarette Smoke Radicals, Hydrogen Peroxide, Peroxynitrate, and Peroxynitrite;Ann. N. Y. Acad. Sci.,1993

2. Nitric oxide, oxidants, and protein tyrosine nitration;Proc. Natl. Acad. Sci. USA,2004

3. Bartesaghi, S., Romero, N., and Radi, R. (2020, September 16). Nitric Oxide and Derived Oxidants. Available online: http://www.novapublishers.org/catalog/product_info.php?products_id=30902.

4. Lipid peroxidation—DNA damage by malondialdehyde;Mutat. Res. Mol. Mech. Mutagen.,1999

5. The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart;Basic Res. Cardiol.,1982

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