Embryonic arsenic exposure reduces intestinal cell proliferation and alters hepatic IGF mRNA expression in killifish (Fundulus heteroclitus).
Embryonic arsenic exposure reduces intestinal cell proliferation and alters hepatic IGF mRNA expression in killifish (Fundulus heteroclitus).
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胚胎砷暴露会降低鳉鱼（Fundulusheteroclitus）的肠细胞增殖并改变肝脏 IGF mRNA 表达。
DOI：
10.1080/15287394.2019.1571465
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Bain,LisaJ
中科院分区：
文献类型：
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作者：
Sims,KaleighC;Schwendinger,KateyL;Szymkowicz,DanaB;Swetenberg,JonathanR;Bain,LisaJ
砷（As）是一种在世界各地的食物和水中发现的有毒物质，研究表明，在生命早期暴露会降低生长。因此，本研究的目标是研究机制，其中作为影响生物体的生长。刀鱼（底heteroclitus）暴露于0，10，50，或200 ppb的作为胚胎，孵化后，饲养在干净的水长达40周。代谢研究表明，鳉鱼生物转化砷，使单甲基化和二甲基化砷分别占总金属的15-17%和45- 61%。通过条件因子（CF）测量的生长在8周龄时显著且呈剂量依赖性降低，但在40周龄时与对照组相似。为了确定观察到的初始降低的潜在机制，检查了肠增殖和形态。砷暴露的鱼表现出显着的1.3至1.5倍减少肠绒毛高度和1.4至1.6倍减少增殖细胞核抗原（PCNA+）肠细胞在所有检查周。此外，CF、PCNA+细胞与肠绒毛高度之间存在显著相关性。在检查鱼是否可以补偿肠道变化时，发现肝脏胰岛素样生长因子1（IGF-1）及其结合蛋白（IGFBP-1）的mRNA表达呈剂量依赖性增加。这些结果表明，胚胎暴露最初减少了生长，而肠细胞增殖仍然减少，鱼似乎通过提高肝脏IGF-1和IGFBP-1的转录水平进行补偿。
Arsenic (As) is a toxicant found in food and water throughout the world, and studies suggested that exposure early in life reduces growth. Thus, the goal of this study was to examine mechanisms by which As impacted organismal growth. Killifish(Fundulus heteroclitus) were exposed to 0, 10, 50, or 200 ppb As as embryos and, after hatching, were reared in clean water for up to 40 weeks. Metabolism studies revealed that killifish biotransform As such that monomethylated and dimethylated arsenicals account for 15–17% and 45–61%, respectively, of the total metal. Growth, as measured by condition factor (CF), was significantly and dose-dependently reduced at 8 weeks of age but was similar to controls by 40 weeks. To determine mechanisms underlying the observed initial decrease, intestinal proliferation and morphology were examined. Arsenic-exposed fish exhibited significant 1.3- to 1.5-fold reduction in intestinal villus height and 1.4- to 1.6-fold decrease in proliferating cell nuclear antigen (PCNA+) intestinal cells at all weeks examined. In addition, there were significant correlations between CF, PCNA+ cells, and intestinal villus height. Upon examining whether fish might compensate for the intestinal changes, it was found that hepatic mRNA expression of insulin-like growth factor 1 (IGF-1) and its binding protein (IGFBP-1) were dose-dependently increased. These results indicate that embryonic exposure initially diminished growth, and while intestinal cell proliferation remained reduced, fish appear to compensate by enhancing transcript levels of hepatic IGF-1 and IGFBP-1.