Methylation levels at IGF2 and GNAS DMRs in infants born to preeclamptic pregnancies

Jing He,Yuan Jiang,Hefeng Huang,Hong Zhang,Cong Han,Min Fang,Danqing Yu,Jiamei Ge,Rong Fang,Xiaoqun Ye,Aiping Zhang,Yun Liu,Minyue Dong

doi:10.1186/1471-2164-14-472

Abstract

BackgroundOffspring of pregnancy complicated with preeclampsia are at high risk for hypertension, stroke and possibly obesity. The mechanisms behind the association of intrauterine exposure to preeclampsia and high risk of health problems in the later life remain largely unknown. The aims of the current investigation were to determine the changes in DNA methylation at IGF2 and GNAS DMR in offspring of preeclamptic pregnancy and to explore the possible mechanisms underlying the association between maternal preeclampsia and high risk for health problems in the later life of their offspring.ResultsUmbilical cord blood was taken from infants born to women of preeclampsia (n=56), gestational hypertension (n=23) and normal pregnancy (n=81). DNA methylation levels of IGF2 and GNAS DMR were determined by Massarray quantitative methylation analysis. Methylation levels at IGF2 DMR were significantly lower in preeclampsia than normal pregnancy. The average methylation level at IGF2 DMR was significantly correlated with preeclampsia even after birth weight, maternal age, gestational age at delivery and fetal gender were adjusted. The difference in methylation level was not significantly different between mild and severe preeclampsia. The methylation level at GNAS DMR was not significantly correlated with birth weight, maternal age, gestational age at delivery, fetal gender, preeclampsia or gestational hypertension.ConclusionsWe concluded preeclampsia induced a decrease in methylation level at IGF 2 DMR, and this might be among the mechanisms behind the association between intrauterine exposure to preeclampsia and high risk for metabolic diseases in the later life of the infants.

Highlights

Offspring of pregnancy complicated with preeclampsia are at high risk for hypertension, stroke and possibly obesity
We found that maternal preeclampsia induced a decrease in DNA methylation level at Insulin-like growth factor2 (IGF2) differentially methylated region (DMR) in infants
The methylation levels at sites 3, 6 and 7 of IGF2 DMR were significantly lower in preeclampsia than normal pregnancy (P=0.045, 0.009 and 0.048, respectively), but the methylation levels at site 4, 9 and 10 did not significantly differ (P>0.05 for all)

Summary

Introduction

Offspring of pregnancy complicated with preeclampsia are at high risk for hypertension, stroke and possibly obesity. The mechanisms behind the association of intrauterine exposure to preeclampsia and high risk of health problems in the later life remain largely unknown. The aims of the current investigation were to determine the changes in DNA methylation at IGF2 and GNAS DMR in offspring of preeclamptic pregnancy and to explore the possible mechanisms underlying the association between maternal preeclampsia and high risk for health problems in the later life of their offspring. Low birth weight is associated with the increased risk of arterial hypertension, carotid arteriosclerosis and mortality caused by coronary heart disease or stroke in adulthood more than 20 years ago [9]. Some investigations indicate that the association of preeclampsia with health problems in later life of offspring is independent of birth weight [3] The mechanisms underlying this association attracted the attention of scientists. Alterations in cardiac structure [10], vascular structure and function [11], sympatho-adrenal function [12], renal function [13], immune function and inflammation [14], and endocrine status [15] have been proposed to be involved in the longterm programming of cardio-vascular diseases in the late life of offspring of preeclamptic pregnancies [1,2], the molecular mechanism remains largely unknown

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Conclusion