Environmental Toxicology Graduate Program, Clemson University, Clemson, SC, United States.
Department of Biological Sciences, Clemson University, Clemson, SC, United States.
Aquat Toxicol. 2018 May;198:276-286. doi: 10.1016/j.aquatox.2018.03.015. Epub 2018 Mar 19.
Arsenic is a contaminant found worldwide in drinking water and food. Epidemiological studies have correlated arsenic exposure with reduced weight gain and improper muscular development, while in vitro studies show that arsenic exposure impairs myogenic differentiation. The purpose of this study was to use Fundulus heteroclitus or killifish as a model organism to determine if embryonic-only arsenic exposure permanently reduces the number or function of muscle satellite cells. Killifish embryos were exposed to 0, 50, 200, or 800 ppb arsenite (As) until hatching, and then juvenile fish were raised in clean water. At 28, 40, and 52 weeks after hatching, skeletal muscle injuries were induced by injecting cardiotoxin into the trunk of the fish just posterior to the dorsal fin. Muscle sections were collected at 0, 3 and 10 days post-injury. Collagen levels were used to assess muscle tissue damage and recovery, while levels of proliferating cell nuclear antigen (PCNA) and myogenin were quantified to compare proliferating cells and newly formed myoblasts. At 28 weeks of age, baseline collagen levels were 105% and 112% greater in 200 and 800 ppb groups, respectively, and at 52 weeks of age, were 58% higher than controls in the 200 ppb fish. After cardiotoxin injury, collagen levels tend to increase to a greater extent and take longer to resolve in the arsenic exposed fish. The number of baseline PCNA(+) cells were 48-216% greater in 800 ppb exposed fish compared to controls, depending on the week examined. However, following cardiotoxin injury, PCNA is reduced at 28 weeks in 200 and 800 ppb fish at day 3 during the recovery period. By 52 weeks, there are significant reductions in PCNA in all exposure groups at day 3 of the recovery period. Based on these results, embryonic arsenic exposure increases baseline collagen levels and PCNA(+) cells in skeletal muscle. However, when these fish are challenged with a muscle injury, the proliferation and differentiation of satellite cells into myogenic precursors is impaired and instead, the fish appear to be favoring a fibrotic resolution to the injury.
砷是一种在饮用水和食物中普遍存在的污染物。流行病学研究表明，砷暴露与体重增加减少和肌肉发育不当有关，而体外研究表明，砷暴露会损害成肌分化。本研究旨在使用美洲鱚作为模型生物，确定胚胎期仅暴露于砷是否会永久性地减少肌肉卫星细胞的数量或功能。将美洲鱚胚胎暴露于 0、50、200 或 800 ppb 亚砷酸盐（As）中，直至孵化，然后将幼鱼在清洁水中饲养。在孵化后 28、40 和 52 周时，通过在鱼背鳍后面的躯干内注射心脏毒素诱导骨骼肌损伤。在 0、3 和 10 天伤后收集肌肉切片。胶原水平用于评估肌肉组织损伤和恢复情况，而增殖细胞核抗原（PCNA）和 myogenin 的水平则用于比较增殖细胞和新形成的成肌细胞。在 28 周龄时，200 和 800 ppb 组的基线胶原水平分别高 105%和 112%，而在 52 周龄时，200 ppb 鱼的胶原水平比对照组高 58%。心脏毒素损伤后，暴露于砷的鱼中的胶原水平倾向于增加更多，并且需要更长的时间才能解决。与对照组相比，800 ppb 暴露的鱼中的基线 PCNA（+）细胞数量高 48-216%，具体取决于检查的周数。然而，在心脏毒素损伤后，28 周龄时 200 和 800 ppb 鱼在恢复期间的第 3 天 PCNA 减少。到 52 周时，所有暴露组在恢复期间的第 3 天 PCNA 均显著减少。基于这些结果，胚胎期砷暴露会增加骨骼肌中的基线胶原水平和 PCNA（+）细胞。然而，当这些鱼受到肌肉损伤的挑战时，卫星细胞的增殖和分化为成肌前体受到损害，相反，鱼似乎更倾向于通过纤维化来解决损伤。
