Maternal late gestation undernutrition in sheep is associated with increased ductus venosus shunting and reduced cerebral oxygen consumption
Date
2026
Authors
Cho, S.K.S.
Saini, B.S.
Darby, J.R.T.
Holman, S.L.
Lock, M.C.
Williams, G.K.
Perumal, R.
Macgowan, C.
Seed, M.
Morrison, J.L.
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Journal article
Citation
Journal of Physiology, 2026; 604(5):2250-2275
Statement of Responsibility
Steven K. S. Cho, Brahmdeep S. Saini, Jack R. T. Darby, Stacey L. Holman, Mitchell C. Lock, Georgia K.Williams, Raj Perumal, ChristopherMacgowan, Mike Seed and Janna L. Morrison
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Abstract
Placental restriction and models of maternal hypoxia result in fetal growth restriction (FGR) with fetal circulatory redistribution, including increased ductus venosus shunting and brain sparing. In contrast, there are limited reports on the effects of fetal nutrient restriction on circulatory redistribution, with data on acute hypoglycaemic challenges or end-organ weights following chronic nutrient restriction. Fetal cardiovascular magnetic resonance (CMR) was employed to define fetal haemodynamics in utero following 25 days of maternal late gestation undernutrition (LGUN). Control ewes received 100% metabolizable energy requirements (MER), whereas LGUN and LGUN + intrafetal glucose supplementation (LGUN + G) ewes received 50% of MER. Fetal CMR was conducted after the dietary regime, and fetal liver was collected the following day. All fetuses were normoxaemic, whereas mean gestational fetal plasma glucose concentrations were lower in both LGUN and LGUN + G fetuses compared to control. There was a negative relationship between relative brain weight and fetal plasma glucose concentration. Biventricular ejection fraction and ductus venosus shunting were increased in LGUN compared to control but were normalized in LGUN + G. Relative left liver lobe weight demonstrated a negative linear relationship with fetal glucose, whereas right-lobe weight revealed a positive relationship. Cerebral oxygen delivery was lower in LGUN compared to control, whereas cerebral oxygen consumption (VO₂) was diminished in both LGUN and LGUN + G compared to control. Cerebral VO₂ correlated positively with fetal glucose. Although intrafetal glucose infusion did not normalize fetal glucose, cardiovascular changes were normalized, providing support for the role of glucose in mediating aspects of FGR physiology in normoxaemic but hypoglycaemic fetuses of LGUN ewes.
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© 2026 The Authors. The Journal of Physiology © 2026 The Physiological Society.