母亲早期生活暴露于低或高叶酸对后代结局和DNA甲基化模式的影响

IF 4.8 Q1 GENETICS & HEREDITY Environmental Epigenetics Pub Date : 2020-11-18 eCollection Date: 2020-01-01 DOI:10.1093/eep/dvaa018
Lundi Ly, Donovan Chan, Mylène Landry, Camille Angle, Josée Martel, Jacquetta Trasler
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引用次数: 11

摘要

卵母细胞发育过程中DNA和组蛋白甲基化的动态模式,由于未来母亲的早期生活环境暴露,呈现出潜在的表观遗传破坏易感时间。我们研究了母体在子宫内暴露于叶酸缺乏和叶酸补充饮食是否会影响卵母细胞,并对下一代后代造成不利的发育和表观遗传影响。雌性BALB/c小鼠(F0)在怀孕前4周以及整个妊娠期和哺乳期被置于四种氨基酸限定饮食中的一种:叶酸控制(啮齿动物推荐每日摄入量;对照)、7倍叶酸缺乏、10倍叶酸补充或20倍叶酸补充的饮食。F1母鼠断奶饲喂Ctrl饲粮,交配产生F2代,并在E18.5检查F2后代的发育和表观遗传异常。20倍叶酸添加组提高了F2 ~ 18.5日龄仔猪的吸收率,减少了产仔数。在所有三个叶酸缺乏和补充组中观察到异常胚胎结局的增加。在7倍叶酸缺乏组、10倍叶酸补充组和20倍叶酸补充组F2后代的胎盘和大脑中发现了细微的全基因组DNA甲基化改变;相比之下,整体和印迹基因甲基化不受影响。研究结果表明,早期女性在卵母细胞成熟之前暴露于低叶酸和高叶酸的环境中,会损害卵母细胞的质量,对下一代的后代产生不利影响,部分原因是DNA甲基化模式的改变。
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Impact of mothers' early life exposure to low or high folate on progeny outcome and DNA methylation patterns.

The dynamic patterning of DNA and histone methylation during oocyte development presents a potentially susceptible time for epigenetic disruption due to early life environmental exposure of future mothers. We investigated whether maternal exposure to folic acid deficient and supplemented diets starting in utero could affect oocytes and cause adverse developmental and epigenetic effects in next generation progeny. Female BALB/c mice (F0) were placed on one of four amino acid defined diets for 4 weeks before pregnancy and throughout gestation and lactation: folic acid control (rodent recommended daily intake; Ctrl), 7-fold folic acid deficient, 10-fold folic acid supplemented or 20-fold folic acid supplemented diets. F1 female pups were weaned onto Ctrl diets, mated to produce the F2 generation and the F2 offspring were examined at E18.5 for developmental and epigenetic abnormalities. Resorption rates were increased and litter sizes decreased amongst F2 E18.5-day litters in the 20-fold folic acid supplemented group. Increases in abnormal embryo outcomes were observed in all three folic acid deficient and supplemented groups. Subtle genome-wide DNA methylation alterations were found in the placentas and brains of F2 offspring in the 7-fold folic acid deficient , 10-fold folic acid supplemented and 20-fold folic acid supplemented groups; in contrast, global and imprinted gene methylation were not affected. The findings show that early life female environmental exposures to both low and high folate prior to oocyte maturation can compromise oocyte quality, adversely affecting offspring of the next generation, in part by altering DNA methylation patterns.

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来源期刊
Environmental Epigenetics
Environmental Epigenetics GENETICS & HEREDITY-
CiteScore
6.50
自引率
5.30%
发文量
0
审稿时长
17 weeks
期刊最新文献
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