Micro and nanoplastic inhalation during pregnancy elicits uterine endothelial dysfunction in Sprague Dawley rats by impeding nitric oxide signaling

Abstract

Micro and nanoplastic (MNP) detection in human tissues demonstrates that exposure at any life stage is inevitable. We have previously demonstrated that pulmonary exposure to this emerging environmental contaminant impairs endothelial function in the uterine vasculature of nonpregnant and pregnant rats. However, neither the mechanism of this dysfunction nor the role of the endothelial-derived vasodilator, nitric oxide (NO), have been interrogated. Therefore, we assessed uterine macro- and microvascular reactivity in Sprague Dawley rats to determine the mechanistic role of NO signaling in endothelial dysfunction after repeated (gestational day 5-19) MNP inhalation during pregnancy. Results identified that MNP exposure reduced fetal growth and impaired endothelial-dependent dilation in the uterine microcirculation, which control placental perfusion and resource availability to the fetus. Levels of activated endothelial nitric oxide synthase (eNOS), phosphorylated on Ser 1176 , were substantially decreased (<50%) in uterine vessels from exposed rats. This suggests MNP inhalation limited NO production and bioavailability. Endothelial function was partially restored by supplementation of arterial segments with the eNOS cofactor tetrahydrobiopterin (BH 4 ), demonstrating that exposed vessels were BH 4 -deficient. Partial restoration was also achieved by incubation with the reducing agent, DTT, suggesting that exposed vessels contained physiologically relevant levels of reactive oxygen and nitrogen species. Increased 3-nitrotyrosine residues and decreased thioredoxin protein expression further suggest MNP fosters nitrosative and oxidative stress in the uterine vasculature, impairing eNOS and endothelial-dependent dilation. These findings implicate eNOS uncoupling as a mechanistic basis for the vascular toxicity of MNPs and the adverse impact of MNPs on fetal development.

Affiliated Institutions

• Environmental and Occupational Health Sciences Institute US
• Rutgers, The State University of New Jersey US

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