Prenatal Exposure To Airborne Particulate Matter On Congenital Cardiac Abnormalities In Fetal Rats

ObjectiveThe present study was to investigate the relationship between intrauterineexposure to different levels of PM suspension（the standard SRM1649a）on thedevelopment of heart in the fetal rat.MethodsOne hundred and twenty five female SD rats were randomized into one ofthe control, low, medium, high and overdose PM exposure groups (n=25),respectively. Rats in Each group were administered with30μl of phosphatebuffered solution (PBS) or resuspended standard PM SRM1649a at0.28,0.74,1.58,5.6μg/μl once every three days for a total of24-26times. Seven weeksafter exposure male and female rats were caged separately by l:2to get access topregnancy. At pregnant d13,15,17,19and postpartum d0.5the fetal hearts weretaken, and the microstructural changes in the fetal heart tissue were observed bylight microscopy and electron microscopy. The mRNA and protein expressionlevels of transcription factor GATA-4and NKX2.5were measured by real-timePCR and Western blotting, resepctively.Results①Under light microscopy, high and overdose PM exposure groupsexhibited abnormally changes in cardiac myocardial cells, nucleus, andchromatin structure. Under electron microscopy, high and overdose PM exposuregroups exhibited abnormal changes in cell membrane, mitochondria, glycogen tocertain degree. In the low and middle PM exposure groups no obvious structuralchanges in the fetal cardiac tissue were seen. ②Compared with the control group, the protein expression levels ofGATA-4and NKX2.5transcription factors in the high and overdose PM exposuregroups were significantly decreased (P<0.05). By multivariate analysis ofvariance, it was shown that the time and dose factors had significant effects onthe levels of GATA-4and NKX2.5transcription factors (P<0.05), but nointeraction between time and dose was found (P>0.05).③Compared with the control group, similarly, the mRNA levels of GATA-4and NKX2.5transcription factors in the high and overdose PM exposure groupshad a significant decline (P<0.05). By multivariate analysis of variance, it wasshown that the time and the dose factors had significant effects on the the mRNAlevels of GATA-4and NKX2.5transcription factors (P<0.05), however, there wasan interaction between the time and dose factors (P<0.05).Conclusions①Intrauterine exposure to different levels of PM can lead pathologicalchanges in heart tissue in the fetal rat. Suggesting that PM exposure may causechanges to the of fetal rat heart mitochondria in structure or function, by thatmethod increasing the oxidative stress and myocardial ischemia, directly orindirectly lead hypoxic-ischemic changes to heart tissue, causing structuralabnormalities to the fetal cardiac tissue.②High to overdose PM exposure may reduce the mRNA and protein levelsof GATA-4and NKX2.5transcription factor. This suggests that PM exposure mayaffect the development of the fetal rat heart, resulting in congenital heart disease,The mechanism may rely on the changes of protein levels of GATA-4andNKX2.5transcription factors through restraining their mRNA expressions.