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

Abstract

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 ∼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.

Identification of the crucial molecular events during the large-scale myoblast fusion in sheep

“…These results will provide the managers of farm animals information on when and how to manipulate the feeding during pregnancy for better postnatal growth. It has been shown that any stress or stimulus to the fetus, such as maternal nutrient constriction, would markedly affect birth weight and postnatal muscle development before 100 days (16,17,68). Around day 85, myoblast differentiation and fusion begins to accelerate, and thus more new myofibers are formed until 100 days; meanwhile the resident primary myofibers increase their size (Fig.…”

The effect of maternal nutrition level during the periconception period on fetal muscle development and plasma hormone concentrations in sheep

“…Conversely, Quigley et al (2005) showed that the cross-sectional area of secondary fibers in ST muscle of singleton fetuses (on day 75 of gestation) was unaffected by maternal feed intake during the periconception period. Similarly, Costello et al (2008) showed that maternal undernutrition during periimplantation period did not influence fiber cross-sectional area in triceps brachii muscle of sheep fetuses. Results of the present study, agreeing with the findings of Wigmore and Stickland (1983), confirm that secondary muscle fiber population in fetal muscles appear to be more sensitive to environmental impacts than primary muscle fiber populations.…”

“…muscle fiber numbers in fetuses compared to low fed ewes (0.5 × maintenance), maternal feed intake during the periconception period did not affect fetal LD, supraspinatus and semitendinosus muscle weights in fetuses. Costello et al (2008) showed that maternal undernutrition in sheep during peri-implantation period reduced total myofibers numbers in triceps brachii muscle of the fetus and fast myofiber (defined as secondary muscle fibers) numbers tended to be lower. Maxfield et al (1998a) reported that plantaris muscle weights of fetuses from co-cultured embryos were increased compared with controls at day 125 of gestation, but coculture did not alter primary fiber number in plantaris muscle at day 61; however, the secondary to primary fiber ratio was increased at both day 61 and day 125.…”

“…Although previous studies have indicated that maternal undernutrition during periconception period can influence fetal myogenesis (Quigley et al, 2005;Costello et al, 2008;Lie et al, 2015), but these studies were conducted in a comparatively wide window of periconception period (~1 month of nutritional insult). As there are reports to suggest that an insult to embryo even for a very short period of time can alter fetal myogenesis in sheep (Maxfield et al, 1998a), we hypothesized that nutritional insult for a narrower period of time during the periconception period than the periods reported in the literature may be enough to influence fetal myogenesis.…”

“…Maternal dietary level affects fetal muscle fiber growth and development during the differentiation period of myogenesis (Costello et al, 2008). Myogenesis and protein synthesis in muscle during periconception period (Lie et al, 2015) have received attention for research as muscle is one of the affected tissues by maternal nutrition level.…”