Embryonic arsenic exposure reduces the number of muscle fibers in killifish (Fundulus heteroclitus)

D’Amico, Angela; Gibson, Alec W; Bain, Lisa J.

doi:10.1016/j.aquatox.2013.11.010

Cited by 13 publications

(15 citation statements)

References 45 publications

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“…When examining growth starting at 16 weeks of age, there were significant decreases of 12–18% in condition factor (growth index) in both 200 and 800ppb embryonically-exposed fish. These results are similar to those seen previously, where embryonic exposures of 800ppb led to an 11% reduction in weight at 16 weeks (D’Amico et al, 2014). These reductions in size continue through 28 weeks of age, are seen in both sexes, and reduction in growth occurs at even lower arsenic concentrations, down to 50ppb arsenic.…”

Section: Discussionsupporting

confidence: 92%

“…That study indicated that arsenic reduced weight in the 8 and 16 week old juvenile fish (D’Amico et al, 2014). The current study was designed to examine the persistence of the weight gain reductions by examining the fish up to 1 year of age, at reproductive maturity.…”

Section: Discussionmentioning

confidence: 92%

“…Appropriate concentrations of arsenic for an embryonic-only exposure were determined previously (D’Amico et al, 2014). The fertilization success (defined as viable embryos 3 days post-fertilization) ranged from 93–97%, and was not significantly different between groups (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…In comparison to rodent models, they can produce large numbers of offspring, allowing for a greater statistical power. Killifish have been previously exposed to 800ppb either during embryogenesis alone or during embryogenesis along with a 16 week grow period had significant reductions in weight (11–17%), and a 14.3% reduction in muscle fiber density (D’Amico et al , 2014). Exposure of killifish to 25ppm arsenic during embryogenesis revealed significant upregulation of skeletal myosin light and heavy chains expression (2.1- and 1.6-fold, respectively) that was coupled with reduced muscle fiber organization and fewer large muscle fibers (1.6- to 7.5-fold reduction) (Gaworecki et al ., 2012).…”

Section: Introductionmentioning

confidence: 99%

“…If arsenic is reducing the number of myofibers formed by impairing proper myogenesis, this may manifest itself in reduced birth weight and weight gain following an embryonic exposure. Indeed, killifish exposed embryonically to 0–5ppm As III were 8–13% smaller at 16 weeks old compared to controls, and their muscle fiber density was decreased by 14–26% (D’Amico et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

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Embryonic-only arsenic exposure in killifish (Fundulus heteroclitus) reduces growth and alters muscle IGF levels one year later

et al. 2017

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Arsenic is a contaminant of drinking water and crops in many parts of the world. Epidemiological studies have shown that arsenic exposure is linked to decreased birth weight, weight gain, and proper skeletal muscle function. The goal of this study was to use killifish (Fundulus heteroclitus) as a model to determine the long-term effects of embryonic-only arsenic exposure on muscle growth and the insulin-like growth factor (IGF) pathway. Killifish embryos were exposed to 0, 50, 200 or 800ppb AsIII from fertilization until hatching. Juvenile fish were reared in clean water and muscle samples were collected at 16, 28, 40 and 52 weeks of age. There were significant reductions in condition factors, ranging from 12–17%, in the fish exposed to arsenic at 16, 28 and 40 weeks of age. However, by 52 weeks, no significant changes in condition factors were seen. Alterations in IGF-1R and IGF-1 levels were assessed as a potential mechanism by which growth was reduced. While there no changes in hepatic IGF-1 transcripts, skeletal muscle cells can also produce their own IGF-1 and/or alter IGF-1 receptor levels to help enhance growth. After a 200 and 800ppb embryonic exposure, fish grown in clean water for 16 weeks had IGF-1R transcripts that were 2.8-fold and 2-fold greater, respectively, than unexposed fish. Through 40 weeks of age, IGF1-R remained elevated in the 200ppb and 800ppb embryonic exposure groups by 1.8–3.9-fold, while at 52 weeks of age, IGF-1R levels were still significantly increased in the 800ppb exposure group. Skeletal muscle IGF-1 transcripts were also significantly increased by 1.9–5.1 fold through the 52 weeks of grow-out in clean by water in the 800ppb embryonic exposure group. Based on these results, embryonic arsenic exposure has long-term effects in that it reduces growth and increases both IGF-1 and IGF-1R levels in skeletal muscle even 1 year after the exposure has ended.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Embryonic-only arsenic exposure in killifish (Fundulus heteroclitus) reduces growth and alters muscle IGF levels one year later

et al. 2017

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Arsenic Promotes NF-Κb-Mediated Fibroblast Dysfunction and Matrix Remodeling to Impair Muscle Stem Cell Function

et al. 2016

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Arsenic is a global health hazard that impacts over 140 million individuals worldwide. Epidemiological studies reveal prominent muscle dysfunction and mobility declines following arsenic exposure; yet, mechanisms underlying such declines are unknown. The objective of this study was to test the novel hypothesis that arsenic drives a maladaptive fibroblast phenotype to promote pathogenic myomatrix remodeling and compromise the muscle stem (satellite) cell (MuSC) niche. Mice were exposed to environmentally relevant levels of arsenic in drinking water before receiving a local muscle injury. Arsenic-exposed muscles displayed pathogenic matrix remodeling, defective myofiber regeneration and impaired functional recovery, relative to controls. When naïve human MuSCs were seeded onto three-dimensional decellularized muscle constructs derived from arsenic-exposed muscles, cells displayed an increased fibrogenic conversion and decreased myogenicity, compared with cells seeded onto control constructs. Consistent with myomatrix alterations, fibroblasts isolated from arsenic-exposed muscle displayed sustained expression of matrix remodeling genes, the majority of which were mediated by NF-κB. Inhibition of NF-κB during arsenic exposure preserved normal myofiber structure and functional recovery after injury, suggesting that NF-κB signaling serves as an important mechanism of action for the deleterious effects of arsenic on tissue healing. Taken together, the results from this study implicate myomatrix biophysical and/or biochemical characteristics as culprits in arsenic-induced MuSC dysfunction and impaired muscle regeneration. It is anticipated that these findings may aid in the development of strategies to prevent or revert the effects of arsenic on tissue healing and, more broadly, provide insight into the influence of the native myomatrix on stem cell behavior.

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Toxicology of arsenic in fish and aquatic systems

et al. 2016

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Embryonic arsenic exposure reduces the number of muscle fibers in killifish (Fundulus heteroclitus)

Cited by 13 publications

References 45 publications

Embryonic-only arsenic exposure in killifish (Fundulus heteroclitus) reduces growth and alters muscle IGF levels one year later

Embryonic-only arsenic exposure in killifish (Fundulus heteroclitus) reduces growth and alters muscle IGF levels one year later

Arsenic Promotes NF-Κb-Mediated Fibroblast Dysfunction and Matrix Remodeling to Impair Muscle Stem Cell Function

Toxicology of arsenic in fish and aquatic systems

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