Fetal glucose availability: a key regulator of the metabolic, hormonal and contractility profiles of the fetal sheep heart
Date
2025
Authors
Bertossa, M.R.
Darby, J.R.T.
Holman, S.L.
Cho, S.K.S.
Meakin, A.S.
Lock, M.C.
Minns, J.A.
Wiese, M.D.
Macgowan, C.K.
Seed, M.
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Journal article
Citation
Journal of Physiology, 2025; 1-23
Statement of Responsibility
Melanie R. Bertossa, Jack R. T. Darby, Stacey L. Holman, Steven K. S. Cho, Ashley S. Meakin, Mitchell C. Lock, Jordan A. Minns, Michael D. Wiese, Christopher K. Macgowan, Mike Seed, and Janna L. Morrison
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DOI
Abstract
There is an association between fetal growth restriction (FGR) and a poor lifetime cardiac health trajectory. Defining the underlying mechanisms will aid in developing interventions to decrease the contribution of FGR-born offspring to the global burden of cardiovascular disease. One cause of FGR is maternal undernutrition. In late-gestation undernutrition (LGUN) fetal glucose supply, a main energy source for the fetal heart, is reduced. This may be a key contributor to altered fetal cardiac development; thus restoration of fetal glucose availability in the LGUN setting may be a viable target for intervention. To investigate the role of glucose availability in fetal heart development, we utilized an established pregnant sheep model of LGUN (50% global nutrient restriction) with or without a continuous intrafetal glucose infusion. LGUN reduced fetal plasma glucose concentrations, resulting in brain sparing that was normalized by intrafetal glucose infusion. LGUN decreased the protein abundance of oxidative phosphorylation complexes 1 and 3; however glucose infusion returned complex 3 abundance to that of controls. LGUN increased the phosphorylation of contractility and hypertrophy marker CAMKII, which was associated with increased left ventricular cardiac output; however intrafetal glucose infusion normalized CAMKII. Our findings demonstrate that glucose plays a specific role in regulating cardiac development in utero, highlighting the importance of adequate maternal nutrition in late gestation.
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© 2025 The Author(s). 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.