Toward an adverse outcome pathway for impaired growth: Mitochondrial dysfunction impairs growth in early life stages of the fathead minnow (Pimephales promelas)

Comp Biochem Physiol C Toxicol Pharmacol. 2018 Jul:209:46-53. doi: 10.1016/j.cbpc.2018.03.009. Epub 2018 Apr 3.

Abstract

Chemical contaminants present in the environment can affect mitochondrial bioenergetics in aquatic organisms and can have substantial effects on individual fitness. As early life stages of fish are particularly vulnerable to environmental contaminants, they are ideal models for examining the relationship between impaired mitochondrial bioenergetics (ATP-dependent respiration, basal oxidative respiration) and apical endpoints such as growth. Here, early life stages of the fathead minnow (Pimephales promelas), an ecologically relevant North American species, were used to investigate the relationship between mitochondrial bioenergetics and growth following perturbation with model mitochondrial toxicants 2,4-dinitrophenol and octylamine. Fathead minnows were exposed to 2,4-dinitrophenol and octylamine at 3 concentrations for 24 h and endpoints related to mitochondrial bioenergetics were measured with the Agilent Seahorse XFe24 Bioanalyzer. In order to link changes in mitochondrial bioenergetics to growth, fathead minnows were exposed to the same chemical contaminants for 7-14 days and growth was measured by measuring total length on a weekly basis. There was a significant correlation between decrease in average length at 14 days and basal respiration (r = 0.997, p = 0.050, n = 3), as well as maximal respiration (r = 0.998, p-value = 0.043, n = 3) for embryos exposed to 2,4 dinitrophenol. For octylamine, ATP production was highly correlated with average length at 7 days (p-value = 0.1) and spare respiratory capacity and average length at 14 days were highly correlated (p-value = 0.1). These data improve understanding of how mitochondrial toxicants impair growth in fish larvae and may be useful for developing an adverse outcome pathway for growth.

Keywords: 2,4-dinitrophenol and octylamine; ATP production; Adverse outcome pathway; Fish early life stages; Growth; Mitochondrial dysfunction.

Publication types

  • Comparative Study

MeSH terms

  • 2,4-Dinitrophenol / toxicity*
  • Adenosine Triphosphate / metabolism
  • Amines / toxicity*
  • Animals
  • Aquaculture
  • Body Size / drug effects
  • Cluster Analysis
  • Cyprinidae / embryology
  • Cyprinidae / growth & development
  • Cyprinidae / physiology*
  • Electron Transport / drug effects
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / physiology
  • Embryonic Development / drug effects*
  • Energy Metabolism / drug effects
  • Hydrogen-Ion Concentration
  • Larva / drug effects*
  • Larva / growth & development
  • Larva / physiology
  • Mitochondria / drug effects*
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Osmolar Concentration
  • Oxygen Consumption / drug effects
  • Reproducibility of Results
  • Toxicity Tests, Acute
  • Water Pollutants, Chemical / toxicity*

Substances

  • Amines
  • Water Pollutants, Chemical
  • Adenosine Triphosphate
  • 2,4-Dinitrophenol
  • octylamine