Sex differences in cardiac fibrosis induced by gestational exposure to polystyrene nanoplastics in mice offspring†

Abstract

The increasing accumulation of plastics in the environment has raised concerns regarding their potential health hazards. Nanoplastics (NPs) can get transported across the placental barrier, resulting in detrimental effects on developing offspring. To date, the effects of maternal exposure to NPs during pregnancy on the cardiac toxicity in adult offspring have not been conclusively evaluated. Herein, the potential for cardiac injury in the progeny of adult mice that were gestationally exposed to 80 nm polystyrene NPs (PS-NPs) at different doses (0, 0.5, 1, and 5 µg µL⁻¹) through oropharyngeal aspiration was investigated. Gestational exposure to PS-NPs resulted in cardiac fibrosis and cardiomyocyte apoptosis, and induced an increase in malondialdehyde (MDA) levels in adult offspring hearts, which were sex-specific and dose-dependent. The mRNA expression levels of estrogen receptor (ER)-related genes, such as Esr1, Esr2, and GPER1, were found to be significantly decreased on exposure to low-dose PS-NPs but elevated on exposure to high-dose PS-NPs in offspring hearts. Furthermore, the magnitude of this elevation in male offspring significantly exceeded compared to that of the female offspring. Additionally, the expression levels of Esr2 and GPER1 in male offspring that were gestationally exposed to high-dose PS-NPs were found to be higher than those observed in female offspring. The observed sex difference in cardiac fibrosis may be correlated with oxidative stress and changes in ER-related gene expression in the offspring's heart. Overall, our study demonstrated that gestational PS-NP exposure induces significant cardiac injury in adult offspring, providing crucial data on the transgenerational effects of PS-NP exposure in mice.