Maternal one carbon metabolism and arsenic methylation in a pregnancy cohort in Mexico.
Maternal one carbon metabolism and arsenic methylation in a pregnancy cohort in Mexico.
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DOI：
10.1038/s41370-018-0041-1
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发表时间：
2018-09
影响因子：
4.5
通讯作者：
Fry RC
中科院分区：
文献类型：
--
作者：
Laine JE;Ilievski V;Richardson DB;Herring AH;Stýblo M;Rubio-Andrade M;Garcia-Vargas G;Gamble MV;Fry RC
产前是接触受污染饮用水中无机砷(IAS)的关键窗口。摄入的IAS经历肝脏甲基化生成单甲基和二甲基砷化合物(分别为MMA和DMAS)，这一过程有助于尿砷(As)的消除。孕妇AS代谢的差异表现为尿中较大比例的MMA和较小比例的DMA是不良分娩结局的危险因素。一碳代谢(OCM)是供应甲基所必需的营养调节途径，在AS代谢中发挥作用，在产前阶段尚未得到充分研究。在这项来自墨西哥戈麦斯帕拉西奥(Gómez Palacio)孕期砷暴露生物标记物的横断面研究中，我们评估了OCM指标(如母亲血清B12、叶酸和同型半胱氨酸(Hcys))与母亲尿液和新生儿脐带血清中IAS及其代谢物水平之间的关系。队列中叶酸充足(叶酸水平和9nmol/L)的患病率很高，99%，而高同型半胱氨酸血症(Hcys水平和GT；10.4μ/L)很低(8%)。然而，74%的妇女表现出B12缺乏(血清水平和148pmol/L)。相关分析证实，与叶酸充足的母亲相比，血清叶酸水平最低三分位数的母亲所生婴儿脐带血清中的%MMA平均水平显著更高。此外，母血Hcys升高与母血总砷、脐血总砷及脐血MMAS%有关。本研究结果提示，母体OCM状态可能影响脐血AS代谢物的分布。
The prenatal period represents a critical window of susceptibility to inorganic arsenic (iAs) exposure from contaminated drinking water. Ingested iAs undergoes hepatic methylation generating mono and di-methyl arsenicals (MMAs and DMAs, respectively), a process that facilitates urinary arsenic (As) elimination. Differences in pregnant women’s metabolism of As as indicated by greater proportions of MMAs and smaller proportions of DMAs in urine are a risk factor for adverse birth outcomes. One carbon metabolism (OCM), the nutritionally-regulated pathway essential for supplying methyl groups, plays a role in As metabolism and is understudied during the prenatal period. In this cross-sectional study from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, we assessed the relationships among OCM indicators (e.g. maternal serum B12, folate, and homocysteine (Hcys)), and levels of iAs and its metabolites in maternal urine and in neonatal cord serum. The prevalence of folate sufficiency (folate levels > 9 nmol/L) in the cohort was high 99%, and hyperhomocysteinemia (Hcys levels > 10.4 μmol/L) was low (8%). However, 74% of the women displayed a deficiency in B12 (serum levels < 148 pmol/L). Association analyses identified that infants born to mothers in the lowest tertile of serum folate had significantly higher mean levels of %MMA in cord serum relative to folate replete women. In addition, elevated maternal Hcys was associated with total As in maternal urine and cord serum as well as cord serum %MMAs. The results from this study indicate that maternal OCM status may influence the distribution of As metabolites in cord serum.
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通讯作者：
Dědina J