Effect of folate deficiency on placental DNA methylation in hyperhomocysteinemic rats
Effect of folate deficiency on placental DNA methylation in hyperhomocysteinemic rats
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DOI：
10.1016/j.jnutbio.2008.01.010
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发表时间：
2009-03-01
影响因子：
5.6
通讯作者：
Chang, Namsoo
中科院分区：
文献类型：
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作者：
Kim, Ji-Myung;Hong, Kyungju;Chang, Namsoo
我们报道了母体叶酸水平可以影响叶酸介导的一碳代谢和胎盘DNA甲基化。将36只雌性Sprague-Dawley大鼠分为以下三个饮食组：补充叶酸（FS; 8 mg/kg叶酸，n=12）、补充同型胱氨酸和叶酸（HFS; 0.3%同型胱氨酸和8 mg/kg叶酸，n=12）和补充同型胱氨酸和叶酸缺乏（HFD; 0.3%同型胱氨酸和无叶酸，n=12）。从交配前4周至妊娠第20天，对动物饲喂实验饲料（每组n=7-9）。HFS饮食增加血浆同型半胱氨酸和胎盘DNA甲基化，但不影响血浆叶酸，维生素B-12，S-腺苷甲硫氨酸（SAM）或S-腺苷同型半胱氨酸（SAH）水平，或SAM/SAH比在肝脏和胎盘相比，FS饮食。HFD饮食诱导血浆叶酸浓度严重降低，血浆同型半胱氨酸水平升高至100 μ mol/L，肝脏SAH增加，胎盘SAM水平和两种组织中SAM/SAH比值降低，同时胎盘DNA甲基化降低。胎盘DNA甲基化与胎盘（γ =0.819）、肝脏（γ =0.7）和血浆（γ =0.752）叶酸水平;血浆同型半胱氨酸水平（γ =-0.688）;肝脏SAH水平（γ =-0.662）和肝脏SAM/SAH比值（γ =0.494）显著相关。这些结果表明，高同型半胱氨酸血症大鼠的母体叶酸状态影响叶酸介导的一碳代谢和甲基库的稳态，这反过来又会通过改变肝脏的甲基化潜力来影响胎盘DNA甲基化。(C)2009 Elsevier Inc. All rights reserved.
We report that the maternal folate status can influence folate-mediated one-carbon metabolism and DNA methylation in the placenta. Thirty-six female Sprague-Dawley rats were divided into the following three dietary groups: folate-supplemented (FS; 8 mg/kg folic acid, n=12), homocystine- and folate-supplemented (HFS; 0.3% homocystine and 8 mg/kg folic acid, n=12) and homocystine-supplemented and folate-deficient (HFD; 0.3% homocystine and no folic acid, n=12). The animals were fed their experimental diets from 4 weeks prior to mating until Day 20 of pregnancy (n=7-9 per group). The HFS diet increased the plasma homocysteine and placental DNA methylation but did not affect plasma folate, vitamin B-12, S-adenosyl methionine (SAM) or S-adenosyl homocysteine (SAH) levels, or the SAM/SAH ratio in the liver and placenta compared with the FS diet. The HFD diet induced severely low plasma folate concentrations, with plasma homocysteine levels increasing up to 100 mu mol/L, and increased hepatic SAH and decreased placental SAM levels and SAM/SAH ratio in both tissues, with a concomitant decrease in placental DNA methylation. Placental DNA methylation was significantly correlated with placental (gamma=0.819), hepatic (gamma=0.7) and plasma (gamma=0.752) folate levels; plasma homocysteine level (gamma=-0.688); hepatic SAH level (gamma=-0.662) and hepatic SAM/SAH ratio (gamma=0.494). These results suggest that the maternal folate status in hyperhomocysteinemic rats influences the homeostasis of folate-mediated one-carbon metabolism and the methyl pool, which would, in turn, affect placental DNA methylation by altering the methylation potential of the liver. (C) 2009 Elsevier Inc. All rights reserved.