Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310006, China.
BMC Genomics. 2013 Jul 12;14:472. doi: 10.1186/1471-2164-14-472.
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.
Umbilical 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.
We 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.
患有子痫前期的孕妇所生后代患高血压、中风和肥胖的风险较高。胎儿在子宫内暴露于子痫前期与后期生命中健康问题高风险之间的关联的机制在很大程度上仍然未知。目前研究的目的是确定子痫前期妊娠后代中 IGF2 和 GNAS DMR 的 DNA 甲基化变化,并探索母体子痫前期与后代后期生活中健康问题高风险之间关联的可能机制。
从患有子痫前期(n=56)、妊娠期高血压(n=23)和正常妊娠(n=81)的孕妇所生婴儿的脐带血中采集了 DNA。通过 Massarray 定量甲基化分析测定 IGF2 和 GNAS DMR 的 DNA 甲基化水平。与正常妊娠相比,子痫前期 IGF2 DMR 的甲基化水平显著降低。IGF2 DMR 的平均甲基化水平在出生后即使在调整了出生体重、母亲年龄、分娩时的胎龄和胎儿性别后,与子痫前期仍显著相关。轻度和重度子痫前期之间的甲基化水平差异无统计学意义。GNAS DMR 的甲基化水平与出生体重、母亲年龄、分娩时的胎龄、胎儿性别、子痫前期或妊娠期高血压均无显著相关性。
我们得出结论,子痫前期诱导 IGF2 DMR 甲基化水平降低,这可能是胎儿在子宫内暴露于子痫前期与后期生命中代谢疾病高风险之间关联的机制之一。