Embryonic-only arsenic exposure alters skeletal muscle satellite cell function in killifish (Fundulus heteroclitus)

Abstract

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.

Expression profile analysis of muscle growth regulation genes and effects of water flow stress on their expression levels in zebrafish

“…The high expression of the MyoD gene may be involved in the regulation of the normal structure and motor function of the tail handle muscle. Desmin is an intermediate lament protein closely related to muscle tissue development and structural stability (Szymkowicz et al, 2018). The high expression of Desmin in zebra sh myocardium, dorsal muscle, and tail handle muscle may be involved in the tissue structure.…”

Chronic arsenite exposure induced skeletal muscle atrophy by disrupting angiotensin II‐melatonin axis in rats

“…Studies have demonstrated that arsenic exposure induced skeletal muscle injury via generating more reactive oxygen species as well as restraining mitophagy and mitochondrial function in mice and duck 10–12 . Moreover, in vivo studies, arsenic exposure reduced the function of muscle satellite cells and thus impaired myogenic differentiation, which maybe mediated by NF‐κB 13,14 . In vitro studies have also confirmed that inorganic arsenic induced cytotoxicity to skeletal muscle cells by inhibiting myogenic differentiation and muscle regeneration and inducing C 2 C 12 myotube atrophy 15 .…”

“…[10][11][12] Moreover, in vivo studies, arsenic exposure reduced the function of muscle satellite cells and thus impaired myogenic differentiation, which maybe mediated by NF-κB. 13,14 In vitro studies have also confirmed that inorganic arsenic induced cytotoxicity to skeletal muscle cells by inhibiting myogenic differentiation and muscle regeneration and inducing C 2 C 12 myotube atrophy. 15 However, the mechanism of skeletal muscle metabolic dysfunction in arsenic-induced skeletal muscle atrophy remains largely unknown.…”