Analysis Of Placental Genomic DNA Methylation And Risk Factors Of Large For Gestational Age

Objective:Birth weight for gestational age can reflect the nutritional status in uterus and the level of development,is the important indicators commonly used for growth,development and health evaluation,sensitive and easy to obtain,some studies have shown that large for gestational(LGA)or small for gestational age(AGA)all can not only increase the risk of the adults with chronic disease(obesity and type 2 diabetes,high blood pressure,etc.),also can have adverse consequences for neonatal physical and cognitive development.Many hypothesized mechanisms have been proposed to contribute to the impaired glucose tolerance or later diabetes in the later of LGA.Similar with SGA,the contribution of epigenetic modifications may be an important mechanism.Such modifications can alter the expression patterns of genes which ultimately work in concert to influence fetal growth.Unlike our genome,the'epigenome' is modifiable by the environment.These epigenetic changes,such as DNA methylation,alterations in the histone code or non-coding RNA,can alter the patterns of gene expression.This study by comparing the factors of family and pregnancy forappropriate for gestational age(AGA)and large for gestational(LGA),and analyzing the change of DNA methylation in placenta,to explore the family and perinatal high-risk factors for birth weight,investigate the epigenetic mechanism of later metabolic change health in LGA infant,provides the basis for the prenatal care and pregnancy management.Methods:A total of 343 pregnant mothers and their 343 newborns were enrolled.Questionnaire was designed and filled by pregnant mothers or fathers.The questionnaires included the basic information of parents and pregnancy details,the informations of the newborns were completed by the obstetrician.According to the gestational age and birth weight of newborn,they were divided into appropriate for gestational age(AGA)group(176 newborns)and LGA group(167 newborns).6 AGA and 6 LGA placenta samples were collected.Analysis the factors of large for gestational age and the total methylation levels between the LGA and AGA groups were analyzed.Results:The differences of fathers' age,mothers' age,pre-gestational weight,weight gain during pregnancy,pre-gestational BMI,BMI gain during pregnancy,gravida,para,and amniotic fluid volume among three groups were significant(p<0.05,respectively).The multiple linear regression analysis showed that LGA was positively correlated with mother's prenatal BMI,BMI gain during pregnancy,para,and amniotic fluid volume.Analysis the methylation levels with 853 307 probes,methylation levels in 17 244 MVPs was significantly different(p<0.05,respectively)between the LGA and AGA groups,and 705 were hypermethylated(>1.7-fold increase)and 351 were hypomethylated(<0.5-fold increase)in LGA samples compared to AGA samples with significantly different.Bump hunting were used to analysis the DMRs between the LGA and AGA groups.We found that revealed 117 DMRs between LGA and AGA groups,among them 54 were hypermethylated and 63 were hypomethylated in LGA samples compared to AGA samples with significantly different(p<0.05).Conclusions:Older parents' age,multiparity,overnutrition before and during pregnancy were the risk factors of LGA.The intrauterine environment may change the gene expression by affecting the gene methylation of the placenta,affecting the fetal development and neonatal weight,and thereby affecting the metablolism after birth.