Single pulmonary nanopolystyrene exposure in late-stage pregnancy dysregulates maternal and fetal cardiovascular function

Abstract

Large-scale production and waste of plastic materials have resulted in widespread environmental contamination by the breakdown product of bulk plastic materials to micro- and nanoplastics (MNPs). The small size of these particles enables their suspension in the air, making pulmonary exposure inevitable. Previous work has demonstrated that xenobiotic pulmonary exposure to nanoparticles during gestation leads to maternal vascular impairments, as well as cardiovascular dysfunction within the fetus. Few studies have assessed the toxicological consequences of maternal nanoplastic (NP) exposure; therefore, the objective of this study was to assess maternal and fetal health after a single maternal pulmonary exposure to polystyrene NP in late gestation. We hypothesized that this acute exposure would impair maternal and fetal cardiovascular function. Pregnant rats were exposed to nanopolystyrene on gestational day 19 via intratracheal instillation. 24 h later, maternal and fetal health outcomes were evaluated. Cardiovascular function was assessed in dams using vascular myography ex vivo and in fetuses in vivo function was measured via ultrasound. Both fetal and placental weight were reduced after maternal exposure to nanopolystyrene. Increased heart weight and vascular dysfunction in the aorta were evident in exposed dams. Maternal exposure led to vascular dysfunction in the radial artery of the uterus, a resistance vessel that controls blood flow to the fetoplacental compartment. Function of the fetal heart, fetal aorta, and umbilical artery after gestational exposure was dysregulated. Taken together, these data suggest that exposure to NPs negatively impacts maternal and fetal health, highlighting the concern of MNPs exposure on pregnancy and fetal development.

Keywords: DOHaD; cardiac ultrasound; fetal growth restriction; intratracheal instillation; micro- and nanoplastics.

Figure 1.

Vascular reactivity in the maternal aorta and uterine artery was assessed by establishing concentration response curves with the endothelial-dependent vasodilator methacholine (A and D), the endothelial-independent vasodilator sodium nitroprusside (B and E), and the vasoconstrictor phenylephrine (C and F). Four-parameter nonlinear regression models were used to assess significant differences in overall reactivity between groups. Data are presented as mean ± SEM, n = 8–9. *Significantly different (p < .05) from saline controls.

Figure 2.

Vascular reactivity in the uterine radial artery was assessed by establishing drug response curves with the endothelial-dependent vasodilator, methacholine (A), the endothelial independent-vasodilator, sodium nitroprusside (B), and the vasoconstrictor, phenylephrine (C). Four-parameter nonlinear regression models were used to assess significant differences in overall reactivity between groups. Data are presented as mean ± SEM, n = 7–8. *Significantly different (p < .05) from saline controls.

Figure 3.

Maternal cardiovascular function was assessed through ultrasound. The maternal aorta and pulmonary artery were examined for diameter (A and C) and velocity (B and D). Data are presented as mean ± SEM, n = 6. *Significantly different (p < .05) from control dams as determined by a two-tailed t-test assuming equal variance between groups.

Figure 4.

Fetal cardiac function was assessed through ultrasound. Fetal heart rate is shown in beats per minute (A). Within the left ventricular outflow tract (LVOT), velocity (B), pressure gradient (C), and stroke distance (D) were measured. The measured parameters represent the average of 3 fetuses for each dam. Data are presented as mean ± SEM, n = 6. *Significantly different (p < .05) from control dams as determined by a two-tailed t-test assuming equal variance between groups.

Figure 5.

Fetoplacental vascular functionality of the fetal aorta and umbilical artery was assessed through ultrasound. Fetal aorta and umbilical artery were examined for diameter (A and C) velocity (B and D). Pressure gradient (E) and stroke distance (F) were measured in the umbilical artery. The measured parameters represent the average of 3 fetuses for each dam. Data are presented as mean ± SEM, n = 12. *Significantly different (p < .05) from control dams as determined by a two-tailed t-test assuming equal variance between groups.