Lesseur Corina, Armstrong David A, Paquette Alison G, Li Zhigang, Padbury James F, Marsit Carmen J
Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH.
Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH.
Am J Obstet Gynecol. 2014 Dec;211(6):654.e1-9. doi: 10.1016/j.ajog.2014.06.037. Epub 2014 Jun 19.
In this study, we aimed to investigate relationships between maternal prepregnancy obesity and gestational diabetes mellitus and placental leptin DNA methylation.
This study comprises data on 535 mother-infant dyads enrolled in the Rhode Island Child Health Study, a prospective cohort study of healthy term pregnancies. Prepregnancy body mass index was calculated from self-reported anthropometric measures and gestational diabetes mellitus diagnoses gathered from inpatient medical records. DNA methylation of the leptin promoter region was assessed in placental tissue collected at birth using quantitative bisulfite pyrosequencing.
In a multivariable regression analysis adjusted for confounders, infants exposed to gestational diabetes mellitus had higher placental leptin methylation (β = 1.89, P = .04), as did those demonstrating prepregnancy obesity (β = 1.17, P = .06). Using a structural equations model, we observed that gestational diabetes mellitus is a mediator of the effects of prepregnancy obesity on placental leptin DNA methylation (β = 0.81, 95% confidence interval, 0.27-2.71).
Our results suggest that the maternal metabolic status before and during pregnancy can alter placental DNA methylation profile at birth and potentially contribute to metabolic programming of obesity and related conditions.
在本研究中，我们旨在调查孕前肥胖与妊娠期糖尿病以及胎盘瘦素DNA甲基化之间的关系。
本研究纳入了罗德岛儿童健康研究中的535对母婴数据，该研究是一项关于健康足月妊娠的前瞻性队列研究。孕前体重指数根据自我报告的人体测量数据计算得出，妊娠期糖尿病诊断则取自住院病历。使用定量亚硫酸氢盐焦磷酸测序法评估出生时采集的胎盘组织中瘦素启动子区域的DNA甲基化情况。
在对混杂因素进行调整的多变量回归分析中，暴露于妊娠期糖尿病的婴儿胎盘瘦素甲基化水平较高（β = 1.89，P = 0.04），孕前肥胖的婴儿也是如此（β = 1.17，P = 0.06）。使用结构方程模型，我们观察到妊娠期糖尿病是孕前肥胖对胎盘瘦素DNA甲基化影响的中介因素（β = 0.81，95%置信区间，0.27 - 2.71）。
我们的结果表明，孕期前后的母亲代谢状态可改变出生时胎盘的DNA甲基化谱，并可能导致肥胖及相关疾病的代谢编程。
