Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity.
Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity.
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DOI：
10.1016/j.taap.2013.12.014
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发表时间：
2014-02-15
影响因子：
3.8
通讯作者：
Finnell, Richard H.
中科院分区：
文献类型：
--
作者：
Wlodarczyk, Bogdan J.;Zhu, Huiping;Finnell, Richard H.
关键词：
已知宫内暴露于砷会对生殖结果产生不利影响。砷致畸性的证据差异很大，取决于个体基因型差异的敏感性。在这项研究中，我们研究了潜在的相互作用之间的5，10-亚甲基四氢叶酸还原酶（Mthfr）基因型和砷胚胎毒性使用Mthfr基因敲除小鼠模型。妊娠母鼠接受砷酸钠治疗，并在E18.5时记录生殖结局，包括：着床、吸收、先天畸形和胎仔出生体重。当Mthfr+/− x Mthfr+/−交配的母鼠接受7.2mg/kg As治疗时，吸收率从背景频率7.2%增加到43.4%。砷处理还引起外部畸形（40.9%），并显着降低平均胎儿出生体重的胎儿，没有任何明显的毒性作用的母兽。当比较不同交配场景（Mthfr+/+ x Mthfr+/−、Mthfr+/− x Mthfr+/−和Mthfr−/− x Mthfr+/−）和砷暴露导致的妊娠结局时，吸收率与Mthfr母体中无效等位基因（0、1或2）的数量呈线性关系。来自无效接合母鼠的胎仔具有最高的外部畸形率（43%）和最低的平均出生体重。当比较As处理后的相互交配（空合子x野生型与野生型x空合子）的结果时，无效母鼠显示出显著更高的吸收和畸形率，沿着较低的胎仔出生体重。母体基因型有助于Mthfr小鼠模型中As胚胎毒性的敏感性。胎儿基因型，但是，似乎并没有影响生殖结果后，在子宫内作为曝光。
In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity vary widely and depend on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. When the dams in Mthfr+/− x Mthfr+/− matings were treated with 7.2mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr+/+ x Mthfr+/−, Mthfr+/− x Mthfr+/− and Mthfr−/− x Mthfr+/−) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote x wild-type versus wild-type x nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure.
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影响因子：
1.9
作者：
Yin, Meng;Dong, Lingyan;Xu, Zhiwei
通讯作者：
Xu, Zhiwei
影响因子：
3.5
作者：
Chen, ZT;Karaplis, AC;Rozen, R
通讯作者：
Rozen, R
影响因子：
168.9
作者：
Muñoz-Moran, E;Dieguez-Lucena, JL;Reyes-Engel, A
通讯作者：
Reyes-Engel, A
DOI：
10.1007/bf01922340
发表时间：
1977-01-01
期刊：
EXPERIENTIA
影响因子：
--
作者：
HANLON, DP;FERM, VH
通讯作者：
FERM, VH
与砷毒性有关的机制。
影响因子：
--
作者：
Singh AP;Goel RK;Kaur T
通讯作者：
Kaur T