Genome-wide DNA Methylation Status In Neonates Affected By Maternal Organochlorine Pesticides Exposure During Pregnancy

Background2,2 bis chlorophenyl-1,1,1-trichloroethane(DDTs)is a kind of common Organochlorine pesticides(OCPs)around environment,and it has a long half-life,which can accumulate in adipose tissue and has biological amplification effect.It is a critical period for the development of fetus during pregnancy,and the epigenome is particularly vulnerable to environmental pollutants in early stages of pregnancy,chemical pollutants exposure may be have adverse impact on the development of fetal immune,nervous,reproductive systems,and so on.However,whether DDTs exposure during pregnancy is one of the earliest etiology of these complex diseases,and whether epigenetic mechanisms can serve as one of the key pathways through exposure to DDTs,whether it will have long-term health consequences for the offspring,the current knowledge of this aspect is still very lack.ObjectivesIn the current study,for the combination of epidemiology,epigenetics and bioinformatics methods,we investigate if different patterns of genome-wide DNA methylation can be detected in the umbilical cord blood of neonates exposed to maternal high level DDTs.Methods1.Participants in this study were selected from Lianhua Hospital.in Xiamen city,China.Pregnant women were asked to complete a questionnaire and be collected samples from umbilical cord and placenta after delivery.2.Capillary gas chromatography(GC)with electron capture detection(ECD)was employed to determine the serum concentrations of DDTs residues concentration in the pregnant women’s peripheral blood and umbilical cord blood.3.According to the detecting results of DDTs levels,we chose 12 mother-child pairs of the highest exposure concentration as case group,and then chose another 12 mother-child pairs who have lowest level DDTs exposure as control group.Then DNA was isolated and the DNA methylation status were analysized by BeadChip.Differential methylation gene analysis was conducted by R software to rasearch the relationship between DDTs exposure during pregnancy and neonates’ health outcome.Results1.The DDTs exposure levels of pregnant women and neonates:(1)150 pregnant women venous serum were detected for the six kind of DDTs.The detection rate of op’-DDT,pp’-DDT,op’-DDE,pp’-DDE,op’-DDD and pp’-DDD,were 29.3%,83.3%,34.7%,82.0%,24.0%and 58.0%.The venous serum median concentration of pp’-DDT,pp’-DDE and pp’-DDD were 1.555ug/ml,0.932ug/ml and 0.072ug/ml;(2)150 umbilical cord serum were detected for the six DDTs.The detection rate of p’-DDT,pp’-DDT,op’-DDE,pp’-DDE,op’-DDD and pp’-DDD were 10.7%,69.3%,45.3%,81.3%,20.7%and 29.3%.The umbilical cord serum median concentration of pp’-DDT and pp’-DDE were 0.406ug/ml and 0.417ug/ml.2.Differential DNA methylation between case group and control group:We identified 1131 CpG sites with significantly different DNA methylation levels in case group relative to control group.The identified sites represented 538 unique genes,12%of these sites were immune-associated genes,which included 689 hypermethylation sites and 442 hypomethylation sites.Gene ontology analysis showed that theses differential methylaiton CpG sites were participated in 7 kind of biological process passages,10 kind of cellular function passages and 8 kind of cellular component passages.Pathway analysis showed a total of five cell pathways related to DDTs prenatal exposure(P value<0.05),including Ribosome biogenesis in eukaryotes,Olfactory transduction,Metabolism of xenobiotics by cytochrome P450,Neurotrophin signaling pathway and Base excision repair.ConclusionsOur study demonstrates a extensive methylation change associated with prenatal DDTs exposure.This DDTs exposure-related methylome exhibits a potential epigenetic regulation involved in the immune regulation,insulin resistance,Olfactory cell signaling pathways,cell cycle and tumorigenesis related gene,ect.It may predict to various complex diseases of these children delivered by mothers who exposed to DDTs during pregnancy.Further research on account of the results obtained from this study will provide more information for identifying specific epigenetic biomarkers in the exploration of these prenatal DDTs exposure-induced diseases.