Impact of periconceptional and preimplantation undernutrition on factors regulating myogenesis and protein synthesis in muscle of singleton and twin fetal sheep

Abstract

In this study, we determined the effect of maternal undernutrition in the periconceptional (PCUN: ∼80 days before to 6 days after conception) and preimplantation (PIUN: 0–6 days after conception) periods on the mRNA and protein abundance of key factors regulating myogenesis and protein synthesis, and on the relationship between the abundance of these factors and specific microRNA expression in the quadriceps muscle of singleton and twin fetal sheep at 135–138 days of gestation. PCUN and PIUN resulted in a decrease in the protein abundance of MYF5, a factor which determines the myogenic lineage, in singletons and twins. Interestingly, there was a concomitant increase in insulin-like growth factor-1 mRNA expression, a decrease in the protein abundance of the myogenic inhibitor, myostatin (MSTN), and an increase in the mRNA and protein abundance of the MSTN inhibitor, follistatin (FST), in the PCUN and PIUN groups in both singletons and twins. These promyogenic changes may compensate for the decrease in MYF5 protein abundance evoked by early embryonic undernutrition. PCUN and PIUN also increased the protein abundance of phosphorylated eukaryotic translation initiation factor binding protein 1 (EIF4EBP1; T70 and S65) in fetal muscle in singletons and twins. There was a significant inverse relationship between the expression of miR-30a-5p, miR-30d-5p, miR-27b-3p, miR106b-5p, and miR-376b and the protein abundance of mechanistic target of rapamycin (MTOR), FST, or MYF5 in singletons or twins. In particular, the expression of miR-30a-5p was increased and MYF5 protein abundance was decreased, in PCUN and PIUN twins supporting the conclusion that the impact of PCUN and PIUN is predominantly on the embryo.

The Effect of Folic Acid Supplementation in the Ovary and Upon Embryo Development

“…Low protein diet (LPD) studies in mice have shown that exposure during the pregnancy or exclusively during preimplantation, not only increases birth and placenta weight, but also increases the blood pressure of mice in adulthood (Kwong et al, 2000;Watkins, Ursell, et al, 2008;Watkins, Wilkins, et al, 2008). Additionality, maternal undernutrition during gestation or preimplantation in sheep has been shown to delay myogenesis in the foetal quadriceps (Lie et al, 2014(Lie et al, , 2015. These studies suggest that the periconceptional period is highly sensitive to the environment, and alterations in this period lead to long-term consequences on future health.…”

Reduced fetal vitamin D status by maternal undernutrition during discrete gestational windows in sheep

“…10 Periconceptional or preimplantation maternal undernutrition disrupted the expression in fetal sheep skeletal muscle of genes regulating myoblast proliferation, differentiation and protein synthesis, insulin signalling and associated microRNA (miRNA). 11,12 While the effect of macronutrient deficiency on fetal cardiovascular control and growth has been characterized, [2][3][4][5][6][7][8] there is very little information on the role played by specific micronutrients such as vitamin D. The micronutrient vitamin D comes from diet (ergocalciferol, D 2 ; cholecalciferol, D 3 ) or the action of sunlight on skin (cholecalciferol, D 3 ). Both forms are hydroxylated in the liver to 25OHD 2 or 25OHD 3 (together in this paper they are referred to as 25OHD total ).…”

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

“…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. Recent studies have shown that maternal nutrition level during premating and early gestation period can change intrauterine conditions and maternal endocrine status (Annett and Carson, 2006;Laporte-Broux et al, 2011).…”

“…Maxfield et al (1998a) reported that early embryo manipulations may have impact on muscle development and/or growth of the fetus and may influence on fetal and neonatal or postnatal size of the offspring. Recently, Lie et al (2015) have demonstrated that maternal undernutrition during the periconception period changes expression of mRNA and/or protein abundance of factors that regulate myogenesis and protein synthesis in the fetal muscle during the late gestation. Moreover, alterations in the intrauterine environment and natural hormone status of the preimplantation embryo may result in developmental adaptations that permanently change the structure, physiology, metabolism, endocrine status and growth of the fetus (Quigley et al, 2005).…”

“…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.…”