Abstract
Skeletal muscle has a notable plasticity and its phenotype is strongly influenced by hormones, transcription factors and physical activity. However, whether the skeletal phenotype could be very prematurely oriented or not since early embryonic stages has never been investigated. Here, we report that the pyruvate as only source of carbohydrate in the culture medium of mouse one cell stage embryo influenced the establishment of the muscular phenotype in adulthood. We found that pyruvate alone, induced changes in the contractile phenotype of the skeletal muscle in a sexually dependent manner. For male mice, a switch to a more glycolytic phenotype was recorded, whereas in female, the pyruvate induced a switch to a more oxidative phenotype. In addition, the influence of pyruvate on the contractile phenotypes was confirmed in two mouse models of muscle hypertrophy: the well-known myostatin deficient mouse (Mstn-/-) and a mouse carrying a specific deletion of p43, a mitochondrial triiodothyronine receptor. Last, to question the link between these adult phenotypes and the early embryonic period, we assessed the levels of two histone H3 post24 translational modifications in presence of pyruvate alone just after the wave of chromatin reprogramming specific of the first cell cycle. We revealed that H3K4 acetylation level was decreased in Mstn-/- 2-cell embryos whereas no difference was found for H3K27 trimethylation level whatever the genotype. These findings demonstrate for the first time that changes in the access of energy substrate during the very first embryonic stage can induce a precocious orientation of skeletal muscle phenotype in adulthood.