The Effects Of Prenatal Exposure To PM_2.5 Extractable Organic Materials On Cardiovascular Development In Offspring

Along with the rapid development of society,the health issues induced by environmental pollution are valued by people.Due to the small particle diameter,PM2.5 enters the alveoli easily through the respiratory system and then scatters over the circulation system,exerting harmful effect on human body.There have been many reports on the effect of PM2.5 on cardiomyogenesis development of offspring.But the effects of the organic components mainly PAHs in PM2.5 on the cardiomyogenesis development of offspring have been less studied.To explore the effects of PM2.5 extractable organic materials(EOM)on fetal heart development,and on adulthood susceptibility to cardiovascular diseases,mice were exposed to the EOM by intra-tracheal administration during 3 weeks before pregnancy and pregnancy period.Three concentrations were set in the experiment,which were 0.18,0.36 and 0.72 μg/pl,respectively.The low concentration corresponds to the second standard of PM2.5 by China’s environmental quality standard,75 μg/m3.The research parameters include general indications of their offspring:litter size and weight of mice,and the sex number of the offspring.Heart HE staining for the offspring in postnatal day 3 and 21 was observed to evaluate the histopathology change,and then transcription factors related to anti-oxidative stress、apoptosis and heart development mRNA expression of the postnatal day 3(PND3)mice were tested.Finally,RNA sequencing was used to screen for differentially expressed genes of four-month-old mice offspring,followed by enrichment of function analysis.The results showed that the general parameters did not change significantly.HE staining of heart tissue showed that the arrangement of ventricular muscle fibers was loose in the PND3 experiment group,aslo the disorganized myocardium and congested blood vessels can be seen in the high concentration group.PND21 offspring in the experimental group had larger ventricular muscle fibers than the control group,and disordered myocardial arrangement can be seen in the middle and high concentration group.The mRNA expression level showed no significant changes in anti-oxidative stress(SOD2,GSH-Px,CAT,HO-1,Nrf2,KEAP1)and apoptotic genes(Caspase3,Caspase8,Bax),But the heart development related genes mRNA expression levels of Hand1 and Hand2 and Gata4 in the low concentration group were decreased,the mRNA expression levels of Tbx20 in the middle concentration group was increased.RNA sequencing showed that the different genes in the experimental group were mainly concentrated in multiple metabolic pathways,which were mainly represented by the down-regulation of endogenous metabolic enzymes in cytochrome P450(CYP)and apolipoprotein genes,and the up-regulation of cyplal.Conclusion:PM2.5 extractable organic materials had adverse effects on the cardiomyogenesis development of mice offspring.Organic extracts induce the heart histopathology change and alter the mRNA expression levels of the related transcription factors in heart development,which suggest that after being exposed on matrix,EOM exerts an influence on fetal heart through placenta and fetal prenatal environment,and derange fetal heart developmental regulation,leading an abnormal structure and function of the fetal heart.Prenatal exposure to EOM also causes inflammation,resulting in decreased myocardial protective function.Prenatal exposure to EOM may also increase the susceptibility to heart diseases and metabolic diseases at adult period,suggesting a far reaching and long term effect.