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Peri-implantation and late gestation maternal undernutrition differentially affect fetal sheep skeletal muscle development

Costello, Paula M., Rowlerson, Anthea, Astaman, Nur Aida, Anthony, Fred Erick W., Sayer, Avan Aihie, Cooper, Cyrus, Hanson, Mark A.. and Green, Lucy R. (2008) Peri-implantation and late gestation maternal undernutrition differentially affect fetal sheep skeletal muscle development The Journal of Physiology, 586, (9), pp. 2371-2379. (doi:10.1113/jphysiol.2008.150987).

Record type: Article


Poor prenatal nutrition is associated with a greater risk of adult glucose intolerance and insulin insensitivity in the offspring. Skeletal muscle is the primary tissue for glucose utilization, and insulin resistance in muscle is the earliest identifiable abnormality in the pre-diabetic patient. We investigated the effect of early and late gestation undernutrition on structure and markers of growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow- and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri-implantation (PI, n = 9; 40%, 1-31 days gestation (dGA) (term approximately 147)) or in late gestation (L, n = 6; 50%, 104-127 dGA). At 127 +/- 1 dGA we measured myofibre and capillary density in the fetal TB and soleus muscles, and mRNA levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary densities were lower in the TB, but not the soleus, of PI and L fetuses. The predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT-4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced myofibre density is consistent with a redistribution of resources at the expense of specific peripheral tissues by early and late gestation undernutrition which may be mediated by a decrease in capillary density. The increase in key regulatory components of glucose uptake following late gestation undernutrition may constitute a short-term compensation to maintain glucose homeostasis in the face of fewer type I (insulin-sensitive) myofibres. However, together these adaptations may influence the risk of later metabolic disease and thus our findings have implications for future strategies aimed at improving maternal diet.

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Published date: 1 May 2008
Organisations: Dev Origins of Health & Disease


Local EPrints ID: 61025
ISSN: 0022-3751
PURE UUID: 3ad70bd1-40e6-41ba-9887-c87f6cc38535
ORCID for Cyrus Cooper: ORCID iD
ORCID for Lucy R. Green: ORCID iD

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Date deposited: 24 Sep 2008
Last modified: 17 Jul 2017 14:22

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Author: Paula M. Costello
Author: Anthea Rowlerson
Author: Nur Aida Astaman
Author: Fred Erick W. Anthony
Author: Avan Aihie Sayer
Author: Cyrus Cooper ORCID iD
Author: Mark A.. Hanson
Author: Lucy R. Green ORCID iD

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