Elevated cortisol concentration in preterm sheep fetuses impacts heart development
Files
(Published version)
Date
2025
Authors
Amanollahi, R.
Holman, S.L.
Bertossa, M.R.
Meakin, A.S.
Clifton, V.L.
Thornburg, K.L.
McMillen, I.C.
Wiese, M.D.
Lock, M.C.
Morrison, J.L.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Experimental Physiology, online, 2025; 110(12):1928-1947
Statement of Responsibility
Reza Amanollahi, Stacey L. Holman, Melanie R. Bertossa, Ashley S. Meakin, Vicki L. Clifton, Kent L. Thornburg, I. Caroline McMillen, Michael D. Wiese, Mitchell C. Lock, Janna L. Morrison
Conference Name
DOI
Abstract
The prepartum rise in cortisol promotes cardiac development and maturation. Here, we investigated the impact of elevated circulating cortisol during mid-late gestation on cardiac growth and metabolism in fetal sheep. Saline or cortisol (2–3 mg in 4.4 mL/24 h) was infused into the fetal jugular vein from 109 to 116 days gestation (dG, term = 150 dG), and fetal heart tissue was collected at 116 dG. Glucocorticoid concentrations, gene and protein expression were measured in fetal left ventricle (LV) tissue. Intrafetal cortisol infusion increased cardiac cortisol concentration but downregulated the protein abundance of glucocorticoid receptor (GR) isoforms (GRα-A, GR-P, GR-A, GRα-D2 and GRα-D3). The gene and protein expression of markers of cardiac hyperplastic growth (IGF1, IGF-1R, TGFβ and AGT) were downregulated, while a protein marker of DNA replication (proliferating cell nuclear antigen) was upregulated by cortisol infusion. Cardiac protein and/or gene expression of complex I of the electron transport chain, SOD2, GLUT-4 (gene and protein), and phosphorylated IRS-1, were upregulated in response to elevated fetal cortisol concentration. Intrafetal cortisol infusion downregulated gene expression of PDK4, which mediates the metabolic switch from glucose to fatty acid metabolism. Cardiac expression of molecular markers involved in cardiovascular protection (SIRT-1, HO1, LAMP1 and SK1) were also downregulated in the cortisol group. In conclusion, these findings suggest that chronic cortisol exposure in preterm fetuses alters heart development, promoting cardiac maturation and potentially increasing the risk of cardiovascular disease later in life if these changes persist into adulthood.
School/Discipline
Dissertation Note
Provenance
Description
First published: 28 April 2025
Access Status
Rights
© 2025 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.