Chronic Cortisol Exposure Reshapes Chromatin Accessibility and Gene Expression: Implications for Growth and Welfare in Rainbow Trout (Oncorhynchus mykiss).
- 1Laboratorio de Biotecnología Molecular, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile.
- 2Interdisciplinary Center for Aquaculture Research-Applied Research (INCAR2), Universidad Andres Bello, Santiago 8370186, Chile.
- 3Centro de Investigacion Marina Quintay (CIMARQ), Universidad Andres Bello, Quintay 2340000, Chile.
Abstract
Cortisol, the principal glucocorticoid in teleosts, coordinates the physiological response to stress by regulating metabolism, protein turnover, and growth. Although the molecular effects of acute cortisol exposure have been extensively characterized, the epigenomic mechanisms underlying skeletal muscle remodeling during prolonged cortisol elevation remain poorly understood. Here, we investigated how chronic cortisol reshapes chromatin accessibility and gene expression in rainbow trout (Oncorhynchus mykiss) skeletal muscle using an integrative ATAC-seq and RNA-seq approach. Fish received a single intraperitoneal injection of cortisol (50 μg g⁻¹ body weight) formulated in coconut oil for sustained hormone release and were sampled after 14 days. Cortisol treatment significantly increased plasma cortisol levels, reduced specific growth rate, and increased skeletal muscle protein carbonylation, indicating impaired growth and oxidative protein damage. ATAC-seq revealed extensive chromatin remodeling, including 126,780 cortisol-specific accessible regions and 3393 genes associated with increased accessibility. These genes were enriched in pathways related to FoxO signaling, autophagy, and apoptosis, whereas regions with reduced accessibility were associated with TGF-β signaling, extracellular matrix interactions, and muscle structural maintenance. RNA-seq identified 2170 differentially expressed genes (844 upregulated and 1326 downregulated), revealing a parallel transcriptional shift toward protein turnover, autophagy, and metabolic adaptation, together with repression of extracellular matrix organization, focal adhesion, integrin signaling, and cytoskeletal organization. Integrative analysis identified 113 genes with coordinated increases and 46 genes with coordinated decreases in chromatin accessibility and transcript abundance, highlighting ubiquitin-mediated proteolysis, mitophagy, FoxO signaling, and metabolic pathways as core components of the chronic cortisol response. Collectively, these findings demonstrate that sustained cortisol elevation drives coordinated epigenomic and transcriptomic remodeling of skeletal muscle, promoting a catabolic phenotype characterized by enhanced protein turnover, oxidative protein damage, and impaired structural maintenance, ultimately contributing to reduced growth and potentially compromising fish welfare under aquaculture conditions.
Related
- Integration of cell-specific gene expression and chromatin accessibility facilitates localization of neurodegenerative risk in microglia
- An autoencoder outperforms two transformers on prediction of gene expression from chromatin accessibility
- Genome-wide loss of chromatin accessibility coexists with selectively elevated RNA abundance in nutrient-starved U2OS cells
- An expanded evolutionary landscape of H3 histones with variants that destabilize nucleosomes and promote chromatin accessibility
- ATACofthesnake: A scalable framework for analyzing multifactorial and time course chromatin accessibility data
BibTeX
@article{larrondo2026chronic,
title = {{Chronic Cortisol Exposure Reshapes Chromatin Accessibility and Gene Expression: Implications for Growth and Welfare in Rainbow Trout (Oncorhynchus mykiss).}},
author = {Leonidas Larrondo and Cristian Reyes and Katalina Llanos-Azócar and Rodrigo Zuloaga and Daniela Aravena-Canales and Camila Godoy-Diaz and Alfredo Molina and Giorgia Daniela Ugarte and Juan Antonio Valdés},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198482},
url = {https://europepmc.org/article/MED/42883731},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chronic Cortisol Exposure Reshapes Chromatin Accessibility and Gene Expression: Implications for Growth and Welfare in Rainbow Trout (Oncorhynchus mykiss).
AU - Leonidas Larrondo
AU - Cristian Reyes
AU - Katalina Llanos-Azócar
AU - Rodrigo Zuloaga
AU - Daniela Aravena-Canales
AU - Camila Godoy-Diaz
AU - Alfredo Molina
AU - Giorgia Daniela Ugarte
AU - Juan Antonio Valdés
PY - 2026
DA - 2026/09/23
JO - International journal of molecular sciences
DO - 10.3390/ijms27198482
UR - https://europepmc.org/article/MED/42883731
AB - Cortisol, the principal glucocorticoid in teleosts, coordinates the physiological response to stress by regulating metabolism, protein turnover, and growth. Although the molecular effects of acute cortisol exposure have been extensively characterized, the epigenomic mechanisms underlying skeletal muscle remodeling during prolonged cortisol elevation remain poorly understood. Here, we investigated how chronic cortisol reshapes chromatin accessibility and gene expression in rainbow trout (Oncorhynchus mykiss) skeletal muscle using an integrative ATAC-seq and RNA-seq approach. Fish received a single intraperitoneal injection of cortisol (50 μg g⁻¹ body weight) formulated in coconut oil for sustained hormone release and were sampled after 14 days. Cortisol treatment significantly increased plasma cortisol levels, reduced specific growth rate, and increased skeletal muscle protein carbonylation, indicating impaired growth and oxidative protein damage. ATAC-seq revealed extensive chromatin remodeling, including 126,780 cortisol-specific accessible regions and 3393 genes associated with increased accessibility. These genes were enriched in pathways related to FoxO signaling, autophagy, and apoptosis, whereas regions with reduced accessibility were associated with TGF-β signaling, extracellular matrix interactions, and muscle structural maintenance. RNA-seq identified 2170 differentially expressed genes (844 upregulated and 1326 downregulated), revealing a parallel transcriptional shift toward protein turnover, autophagy, and metabolic adaptation, together with repression of extracellular matrix organization, focal adhesion, integrin signaling, and cytoskeletal organization. Integrative analysis identified 113 genes with coordinated increases and 46 genes with coordinated decreases in chromatin accessibility and transcript abundance, highlighting ubiquitin-mediated proteolysis, mitophagy, FoxO signaling, and metabolic pathways as core components of the chronic cortisol response. Collectively, these findings demonstrate that sustained cortisol elevation drives coordinated epigenomic and transcriptomic remodeling of skeletal muscle, promoting a catabolic phenotype characterized by enhanced protein turnover, oxidative protein damage, and impaired structural maintenance, ultimately contributing to reduced growth and potentially compromising fish welfare under aquaculture conditions.
SN - 1422-0067
ER -