Costello, P., Rowlerson, A., Braddick, L., Burrage, D., Cooper, C., Hanson, M.A., Ahie Sayer, A. and Green, L.R. (2006) Fetal skeletal muscle fibre number and type are altered by early and late gestation matetrnal undernutrition in sheep. Procedings of the Physiological Society, 3 (C116).
Abstract
Epidemiological studies have shown that small size at birth is associated with reduced muscle strength (Sayer et al. 2004) and type 2 diabetes (Hales et al. 1991) in adulthood. In sheep, reduced early gestation maternal nutrient intake reduces fetal skeletal muscle fibre number (Zhu et al. 2004) and alters myofibre composition in postnatal life (Fahey et al. 2005). Insulin resistance is associated with a shift towards a higher proportion of the relatively insulin-resistant type 2 fast-twitch fibres at the expense of the insulin-sensitive type 1 slow-twitch fibres (Marin et al. 1994). In this study we investigated the effect of early or late gestation nutrient restriction on muscle fibre number and type in late gestation fetal sheep. Pregnant Welsh Mountain ewes of uniform body weight were housed individually, and received either, 100% of total nutrient requirements throughout gestation (C, n=6: female (f)=3, male (m)=3), 40% for first 30 days gestation (dGA) (ER, n=8: f=3, m=5) or 50% from 104 dGA until post mortem (LR, n=7: f=3, m=4), with 100% requirements at all other times. All fetuses were singletons. At ±127 dGA (term ~147 dGA) ewes were killed by an overdose of barbiturate (i.v., 145 mg/kg) and the fetal triceps brachii removed and immersed in freezing isopentane. A 10 ?m section was cut, stained with anti-fast skeletal myosin and five random fields (magnification x40) were captured. Fibre density, type and cross-sectional area (CSA) were measured and analysed by ANOVA with Bonferroni post-hoc tests. Data are expressed as mean ± SEM. The total density of myofibres was reduced in both the ER (p<0.01) and LR (p<0.05) compared to C fetuses (C, 3869 ± 318; ER, 3013 ± 453; LR, 3075 ± 535.6 fibres mm-2). Slow fibre density was significantly lower in LR (p<0.05), but not ER fetuses (C, 603 ± 195; ER 494 ± 99; LR 370 ± 122 fibres mm-2). Fast fibre density tended to be lower in ER (p=0.07) but not LR fetuses (C, 3286 ± 402; ER 2680 ± 399; LR 2855 ± 557 fibres mm-2). Fast and slow fibre CSA was similar in all nutritional groups. These data show that reduced maternal nutrition in either the peri-implantation period or late gestation affects myofibre density, but that late gestation nutrient restriction has particularly profound effects on slow-twitch fibres. These observations may have important implications for understanding the determinants of muscle strength and glucose tolerance in later life.
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