Nakanishi Misao, Funahashi Nobuaki, Fukuoka Hideoki, Nammo Takao, Sato Yuichi, Yoshihara Hajime, Oishi Hajime, Tanaka Mamoru, Yano Tetsu, Minoura Shigeki, Kato Norihiro, Yasuda Kazuki
Department of Obstetrics and Gynecology, Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan.
Department of Obstetrics and Gynecology, Keio University Graduate School of Medicine, Tokyo, Japan.
J Obstet Gynaecol Res. 2021 Feb;47(2):734-744. doi: 10.1111/jog.14599. Epub 2020 Dec 9.
We performed a birth cohort study involving 124 mother-infant pairs to investigate whether placental DNA methylation is associated with maternal choline status and fetal development.
Plasma choline concentration was assayed longitudinally in the 1st and 3rd trimesters and at term-pregnancy in mothers and cord blood. Placental DNA methylation was measured for 12 target candidate genes that are related to fetal growth, adipogenesis, lipid and energy metabolism, or long interspersed nuclear elements.
Higher maternal plasma and cord blood choline levels at term tended to associate with lower birthweight (r = -0.246, P < 0.013; r = -0.290, P < 0.002) and body mass index (BMI) at birth (r = 0.344, P < 1E-3; r = -0.360, P < 1E-3). The correlation between maternal plasma choline level and cord blood choline level was relatively modest (r = 0.049, P = 0.639). There was an inverse correlation between placental DNA methylation at the retinoid X receptor alpha (RXRA) gene and maternal plasma choline level (r = -0.188 to r = -0.452, P = 0.043 to P < 1E-3 at three points). RXRA methylation level was positively associated with birthweight and BMI at birth (r = 0.306, P = 0.001; r = 0.390, P < 1E-3). Further, RXRA methylation was inversely correlated with RXRA gene expression level (r = 0.333, P < 1E-3).
Our results suggest that the association between maternal choline status and placental RXRA methylation represents a potential fetal programing mechanism contributing to fetal growth.
我们开展了一项涉及124对母婴的出生队列研究，以调查胎盘DNA甲基化是否与母亲胆碱状态及胎儿发育相关。
在孕早期、孕晚期及足月时纵向检测母亲血浆和脐血中的胆碱浓度。对12个与胎儿生长、脂肪生成、脂质和能量代谢或长散在核元件相关的目标候选基因进行胎盘DNA甲基化检测。
足月时母亲血浆和脐血中较高的胆碱水平往往与较低的出生体重（r = -0.246，P < 0.013；r = -0.290，P < 0.002）及出生时的体重指数（BMI）相关（r = 0.344，P < 1E-3；r = -0.360，P < 1E-3）。母亲血浆胆碱水平与脐血胆碱水平之间的相关性相对较弱（r = 0.049，P = 0.639）。维甲酸X受体α（RXRA）基因的胎盘DNA甲基化与母亲血浆胆碱水平呈负相关（三个时间点的r值分别为-0.188至-0.452，P值分别为0.043至P < 1E-3）。RXRA甲基化水平与出生体重及出生时的BMI呈正相关（r = 0.306，P = 0.001；r = 0.390，P < 1E-3）。此外，RXRA甲基化与RXRA基因表达水平呈负相关（r = 0.333，P < 1E-3）。
我们的结果表明，母亲胆碱状态与胎盘RXRA甲基化之间的关联代表了一种潜在的胎儿编程机制，有助于胎儿生长。
