Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans
Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans
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DOI：
10.1096/fj.12-207894
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发表时间：
2012-08-01
期刊：
影响因子：
4.8
通讯作者：
Caudill, Marie A.
中科院分区：
文献类型：
--
作者：
Jiang, Xinyin;Yan, Jian;Caudill, Marie A.
甲基供体的宫内可获得性，如胆碱，可能会改变胎儿的表观遗传标记，并导致整个生命过程中可持续的功能改变。下丘脑-垂体-肾上腺(HPA)轴调节皮质醇的产生，对围产期的表观遗传程序敏感。作为对妊娠晚期妇女进行的12周剂量-反应胆碱喂养研究的延伸，我们调查了母亲摄入胆碱(930 mg/d比480 mg/d)对胎盘和脐带静脉血中皮质醇调节基因的表观遗传状态及其表达的影响。孕妇胆碱摄入量越高，胎盘促肾上腺皮质激素释放激素和糖皮质激素受体基因启动子甲基化水平越高，胎盘促肾上腺皮质激素释放激素转录丰度越低(P=0.002.0 4)，脐血白细胞促肾上腺皮质激素释放激素和糖皮质激素受体启动子甲基化水平越低(P=0.0 5，P=0.0 4)，脐血皮质醇甲基化水平降低33%(P=0.0 7)。此外，930 mg胆碱/d组胎盘整体DNA甲基化和组蛋白H3赖氨酸9(H3K9me2)甲基化水平较高(P=0.02)，部分胎盘甲基转移酶的表达也较高(P=0.02)。这些数据共同表明，人类母体胆碱摄入调节调节胎儿HPA轴反应性的基因的表观遗传状态以及胎儿衍生组织的表观基因组状态。-酱，X.，严，J.，West，A.，Perry，C.A.，Malysheva，OV.，Dcomamatla，S.，Pressman，E.，Vermeylen，F.，Caudill，M.A.母体胆碱摄入改变了人类胎儿皮质醇调节基因的表观遗传状态。FASE B J.26,3563-3574(2012)。Www.fasebj.org
The in utero availability of methyl donors, such as choline, may modify fetal epigenetic marks and lead to sustainable functional alterations throughout the life course. The hypothalamic-pituitary-adrenal (HPA) axis regulates cortisol production and is sensitive to perinatal epigenetic programming. As an extension of a 12-wk dose-response choline feeding study conducted in third-trimester pregnant women, we investigated the effect of maternal choline intake (930 vs. 480 mg/d) on the epigenetic state of cortisol-regulating genes, and their expression, in placenta and cord venous blood. The higher maternal choline intake yielded higher placental promoter methylation of the cortisol-regulating genes, corticotropin releasing hormone (CRH; P = 0.05) and glucocorticoid receptor (NR3C1; P = 0.002); lower placental CRH transcript abundance (P = 0.04); lower cord blood leukocyte promoter methylation of CRH (P = 0.05) and NR3C1 (P = 0.04); and 33% lower (P = 0.07) cord plasma cortisol. In addition, placental global DNA methylation and dimethylated histone H3 at lysine 9 (H3K9me2) were higher (P = 0.02) in the 930 mg choline/d group, as was the expression of select placental methyltransferases. These data collectively suggest that maternal choline intake in humans modulates the epigenetic state of genes that regulate fetal HPA axis reactivity as well as the epigenomic status of fetal derived tissues.-Jiang, X., Yan, J., West, A. A., Perry, C. A., Malysheva, O. V., Devapatla, S., Pressman, E., Vermeylen, F., Caudill, M. A. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J. 26, 3563-3574 (2012). www.fasebj.org