Back to Search
Start Over
Gestational exposure to air pollutants perturbs metabolic and placenta-fetal phenotype.
- Source :
-
Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2024 Sep; Vol. 128, pp. 108657. Date of Electronic Publication: 2024 Jul 16. - Publication Year :
- 2024
-
Abstract
- Air pollution (AP) is detrimental to pregnancies including increasing risk factors of gestational diabetes mellitus. We hypothesized that exposure to AP causes cardiovascular and metabolic disruption thereby altering placental gene expression, which in turn affects the placental phenotype and thereby embryonic/fetal development. To test this hypothesis, we investigated the impact of intra-nasal instilled AP upon gestational day 16-19 maternal mouse cardiovascular and metabolic status, placental nutrient transporters, and placental-fetal size and morphology. To further unravel mechanisms, we also examined placental total DNA 5'-hydroxymethylation and bulk RNA sequenced gene expression profiles. AP exposed pregnant mice and fetuses were tachycardic with a reduction in maternal left ventricular fractional shortening and increased uterine artery with decreased umbilical artery systolic peak velocities. In addition, they were hyperglycemic, glucose intolerant and insulin resistant, with changes in placental glucose (Glut3) and fatty acid (Fatp1 & Cd36) transporters, and a spatial disruption of cells expressing Glut10 that imports L-dehydroascorbic acid in protecting against oxidative stress. Placentas revealed inflammatory cellular infiltration with associated cellular edema and necrosis, with dilated vascular spaces and hemorrhage. Placental and fetal body weights decreased in mid-gestation with a reduction in brain cortical thickness emerging in late gestation. Placental total DNA 5'-hydroxymethylation was 2.5-fold higher, with perturbed gene expression profiles involving key metabolic, inflammatory, transcriptional, cellular polarizing and processing genes and pathways. We conclude that gestational exposure to AP incites a maternal inflammatory response resulting in features mimicking maternal gestational diabetes mellitus with altered placental DNA 5'-hydroxymethylation, gene expression, and associated injury.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Female
Pregnancy
Animals
Maternal Exposure adverse effects
Phenotype
Mice, Inbred C57BL
DNA Methylation drug effects
Mice
5-Methylcytosine analogs & derivatives
5-Methylcytosine metabolism
Fetus drug effects
Fetus metabolism
Fetal Development drug effects
Placenta metabolism
Placenta drug effects
Air Pollutants toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1873-1708
- Volume :
- 128
- Database :
- MEDLINE
- Journal :
- Reproductive toxicology (Elmsford, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 39002939
- Full Text :
- https://doi.org/10.1016/j.reprotox.2024.108657