Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA.
School of Medicine, University of California, San Francisco, San Francisco, California, USA.
Environ Mol Mutagen. 2021 Aug;62(7):388-398. doi: 10.1002/em.22452. Epub 2021 Jul 31.
Maternal fat intake during pregnancy affects fetal growth, but mechanisms underlying this relationship are unclear. We performed an exploratory study of the associations of fat consumption during pregnancy with cord blood DNA methylation of the insulin-like growth factor 2 (IGF2) and H19 genes. We used data from 96 uncomplicated full-term pregnancies of mothers of whom majority had normal body mass index (BMI) (66%) in Project Viva, a prospective pre-birth cohort. We assessed maternal diet with validated food frequency questionnaires during the first and second trimesters and measured DNA methylation in segments of the IGF2- and H19-differentially methylated regions (DMRs) by pyrosequencing DNA extracted from umbilical cord blood samples. Mean (SD) age was 32.8 (4.1) years and prepregnancy BMI was 24.0 (4.4) kg/m . Mean DNA methylation was 56.3% (3.9%) for IGF2-DMR and 44.6% (1.9%) for H19-DMR. Greater first trimester intake of omega-6 polyunsaturated fat (effect per 1% of calories at the expense of carbohydrates) was associated with lower DNA methylation of IGF2-DMR (-1.2%; 95% confidence interval [CI]: -2.2%, -0.2%) and higher DNA methylation at H19-DMR (0.8%; 95% CI: 0.3%, 1.3%). On the other hand, greater first trimester intake of omega-3 polyunsaturated fat was associated with lower DNA methylation of the H19-DMR (-4.3%; 95% CI: -7.9%, -0.8%). We did not find significant associations of IGF2 and H19 methylation with IGF2 cord blood levels. Our findings suggest that early prenatal fat intake (omega-3, omega-6, and saturated fatty acids) may influence DNA methylation at the IGF2 and H19 locus, which could impact fetal development and long-term health.
孕妇在怀孕期间的脂肪摄入量会影响胎儿的生长，但这种关系的机制尚不清楚。我们对怀孕期间脂肪消耗与脐带血中胰岛素样生长因子 2 (IGF2)和 H19 基因的 DNA 甲基化之间的关联进行了探索性研究。我们使用了来自 Viva 项目的 96 例无并发症的足月妊娠母亲的数据，这些母亲大多数的体重指数 (BMI) 在正常范围内 (66%)。我们使用经过验证的食物频率问卷在妊娠的第一和第二阶段评估了母亲的饮食，并用焦磷酸测序法测量了从脐带血样中提取的 IGF2-和 H19-差异甲基化区域 (DMR) 中的 DNA 甲基化程度。平均（SD）年龄为 32.8（4.1）岁，孕前 BMI 为 24.0（4.4）kg/m。IGF2-DMR 的平均 DNA 甲基化程度为 56.3%（3.9%），H19-DMR 的平均 DNA 甲基化程度为 44.6%（1.9%）。第一孕期消耗的多不饱和脂肪酸（每消耗 1%的卡路里，以牺牲碳水化合物为代价）与 IGF2-DMR 的 DNA 甲基化程度降低（-1.2%；95%置信区间 [CI]：-2.2%，-0.2%）和 H19-DMR 的 DNA 甲基化程度升高（0.8%；95%CI：0.3%，1.3%）相关。另一方面，第一孕期摄入的更多的 ω-3 多不饱和脂肪酸与 H19-DMR 的 DNA 甲基化程度降低有关（-4.3%；95%CI：-7.9%，-0.8%）。我们没有发现 IGF2 和 H19 甲基化与 IGF2 脐带血水平之间存在显著关联。我们的研究结果表明，早期产前脂肪摄入（ω-3、ω-6 和饱和脂肪酸）可能会影响 IGF2 和 H19 基因座的 DNA 甲基化，从而影响胎儿的发育和长期健康。
