Effect of maternal nutrient restriction in sheep on the development of fetal skeletal muscle

Mei-Jun Zhu; Stephen P Ford; Peter W Nathanielsz; Min Du

doi:10.1095/biolreprod.104.034561

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Effect of maternal nutrient restriction in sheep on the development of fetal skeletal muscle

Journal article

Open access

Peer reviewed

Effect of maternal nutrient restriction in sheep on the development of fetal skeletal muscle

Mei-Jun Zhu, Stephen P Ford, Peter W Nathanielsz and Min Du

Biology of reproduction, Vol.71(6), pp.1968-1973

12/2004

DOI: https://doi.org/10.1095/biolreprod.104.034561

Handle:

https://hdl.handle.net/2376/115575

PMID: 15317692

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Abstract

Calcium-Binding Proteins - metabolism

Protein Kinases - metabolism

Signal Transduction

Pregnancy, Animal - physiology

Fetus - metabolism

Ubiquitin - metabolism

Pregnancy

Animals

Animal Nutritional Physiological Phenomena

Muscle Fibers, Skeletal - ultrastructure

Female

Fetus - ultrastructure

Food Deprivation

Sheep

TOR Serine-Threonine Kinases

Muscle, Skeletal - embryology

The effect of maternal nutrient restriction on mTOR (mammalian target of rapamyosin) signaling and the ubiquitin system as well as their possible relation to growth of fetal muscle was determined. Ewes were fed to 50% (nutrient-restricted) or 100% (control-fed) of total digestible nutrients (National Research Council requirement) from Days 28 to 78 of gestation. Ewes were killed at Day 78 of gestation, and the fetal longissimus dorsi muscle was sampled for the measurement of mTOR, ribosomal protein S6, AMP-activated protein kinase (AMPK), calpastatin, and protein ubiquitylation. No difference was observed in the content of mTOR and ribosomal protein S6, but the phosphorylation of mTOR at Ser2448 and ribosomal protein S6 at Ser235/336 were reduced (P <0.05) in muscle from nutrient-restricted fetuses. Because phosphorylation of mTOR and ribosomal protein S6 up-regulates protein translation, these results show that nutrient restriction down-regulates protein synthesis in fetal muscle. No difference in AMPK activity was detected. The lack of difference in calpastatin and ubiquitylized protein content shows that nutrient restriction did not affect degradation of myofibrillar proteins in fetal muscle. Fetuses of nutrient-restricted ewes showed retarded development of muscles and skeleton. Muscle from nutrient-restricted fetuses contained fewer secondary myofibers than muscle from control fetuses, and the average area of fasciculi was smaller (P <0.05). The decreased number of secondary myofibers in nutrient-restricted fetuses may result from the decreased mTOR signaling. Lower activation of mTOR signaling in nutrient-restricted fetuses may reduce the proliferation of myoblasts and, thus, reduce the formation of secondary myofibers. This decrease in secondary myofibers in fetuses may predispose fetuses to metabolic diseases, such as diabetes and obesity, in their postnatal lives.

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Title: Effect of maternal nutrient restriction in sheep on the development of fetal skeletal muscle
Creators: Mei-Jun Zhu - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, Wyoming 82071, USA
Stephen P Ford
Peter W Nathanielsz
Min Du
Publication Details: Biology of reproduction, Vol.71(6), pp.1968-1973
Academic Unit: Animal Sciences, Department of
Publisher: United States
Grant note: HD21350 / NICHD NIH HHS
Identifiers: 99900547628001842
Language: English
Resource Type: Journal article