Maternal exposure to ambient PM 2.5 exaggerates fetal cardiovascular maldevelopment induced by homocysteine in rats.

Maternal exposure to airborne particulate matter with aerodynamic diameter <2.5 µm (PM _2.5 ) during pregnancy and lactation periods is associated with filial congenital cardiovascular diseases. This study aimed to investigate the toxic effects of maternal exposure to ambient levels of PM _2.5 on filial cardiovascular maldevelopment induced by homocysteine. Using a 2 × 2 factorial design, rats were randomized into four groups and were exposed to ambient PM _2.5 or filtered air (FA) throughout the pregnancy and lactation periods coupled with the administration of either homocysteine (HCY) or normal saline (NS) daily from gestation days 8-10. Morphological changes in the heart, myocardial apoptosis, expressions of cardiac progenitor transcriptional factors, and levels of cytokines were investigated in the offspring. The apoptosis-like changes in the myocardium were seen in the FA plus HCY-treated group and more obviously in the PM _2.5 plus HCY-treated group, which was in accordance with an increased myocardial apoptosis rate in the two groups. PM _2.5 exposure resulted in significantly decreased Nkx2-5 protein level and GATA4 and Nkx2-5 mRNA expressions, and significantly increased TNF-α and IL-1β levels. There were significant interactions between PM _2.5 exposure and HCY-treatment that PM _2.5 exposure reduced Nkx2-5 protein levels and GATA4 and Nkx2-5 mRNA expressions in the HCY-treated groups. These results suggest that maternal exposure to PM _2.5 , even at the ambient levels in urban regions in China, exaggerates filial cardiovascular maldevelopment induced by HCY in a murine model, exacerbating structural abnormalities in the filial cardiac tissue, which is possibly associated with oxidative stress and reduced GATA4 and Nkx2-5 transcription factor expressions. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 877-889, 2017.
(© 2016 Wiley Periodicals, Inc.)