Scales Tell a Story on the Stress History of Fish

PLoS One. 2015 Apr 29;10(4):e0123411. doi: 10.1371/journal.pone.0123411. eCollection 2015.


Fish faced with stressful stimuli launch an endocrine stress response through activation of the hypothalamic-pituitary-interrenal (HPI-) axis to release cortisol into the blood. Scientifically validated biomarkers to capture systemic cortisol exposure over longer periods of time are of utmost importance to assess chronic stress in governmental, wildlife, aquaculture and scientific settings. Here we demonstrate that cortisol in scales of common carp (Cyprinus carpio L.) is the long-sought biomarker for chronic stress. Undisturbed (CTR) and daily stressed (STRESS) carp were compared. Dexamethasone (DEX) or cortisol (CORT) fed fish served as negative and positive controls, respectively. Scale cortisol was quantified with a validated ultra-performance liquid chromatography tandem mass spectrometry method. An increase in scale cortisol content was found in STRESS and CORT but not in CTR and DEX fish. Scale cortisol content reflects its accumulation in a stressor and time dependent manner and validates the scale cortisol content as biomarker for chronic stress. Plasma analyses confirmed that (i) CTR, DEX and CORT treatments were effective, (ii) plasma cortisol of STRESS fish showed no signs of chronic HPI-axis activation, and (iii) plasma cortisol is a poor predictor for chronic stress. The expression of HPI key genes crf, pomc, and star were up-regulated in STRESS fish in the absence of a plasma cortisol response, as was the target gene of cortisol encoding subunit α1 of the Na+/K+-ATPase in gills. When lost, scales of fish regenerate fast. Regenerated scales corroborate our findings, offering (i) unsurpassed time resolution for cortisol incorporation and as such for stressful events, and (ii) the possibility to investigate stress in a well defined and controlled environment and time frame creating novel opportunities for bone physiological research. We conclude that the cortisol content in ontogenetic and regenerated scales is an innovative biomarker for chronic stress offering ample applications in science and industry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carps / blood
  • Carps / genetics
  • Carps / physiology*
  • Dexamethasone / analysis
  • Dexamethasone / blood
  • Dexamethasone / metabolism
  • Fish Proteins / genetics
  • Gene Expression Regulation
  • Hydrocortisone / analysis
  • Hydrocortisone / blood
  • Hydrocortisone / metabolism*
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Stress, Physiological*


  • Fish Proteins
  • Dexamethasone
  • Sodium-Potassium-Exchanging ATPase
  • Hydrocortisone

Grant support

This research was financially supported by the Institute for Agricultural and Fisheries Research, the Laboratory of Food Analysis of the Faculty of Pharmaceutical Sciences of Ghent University, the Department of Morphology of the Faculty of Veterinary Medicine of Ghent University, and the Department of Animal Physiology of Radboud University Nijmegen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.