Postnatal development of skeletal muscle in IUGR pigs: morphofunctional phenotype and molecular mechanisms

Abstract

Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of the fetus full growth potential and occurs in a natural and severe manner in pigs. Knowledge on skeletal muscle morphofunctional phenotype and its molecular regulation in IUGR pigs is important to understand postnatal muscle development and may help the establishment of therapies to improve skeletal muscle growth in those individuals. To investigate the impairment of skeletal muscle postnatal development due to IUGR, we evaluated the histomorphometrical pattern of the semitendinosus muscle, the Myosin Heavy Chain (embryonic, I, IIa, IIb and IIx MyHC) fiber composition and the relative expression of genes related to myogenesis, adipogenesis and growth during three specific periods: postnatal myogenesis (newborn to 100 days of age), postnatal development (newborn to 150 days of age), and hypertrophy (100 days to 150 days of age), comparing IUGR and normal birth weight (NW) pigs. Growth restriction in utero affected muscle fiber diameter, total fiber number and muscle cross sectional area which were smaller in IUGR pigs at birth (P < 0.05). Even though the percentage of MyHC-I myofibers was higher in IUGR females at birth (P < 0.05), in older gilts, a lower percentage of MyHC-IIx isoform (P < 0.05) and the presence of emb-MyHC were also observed in that experimental group. Regarding the pattern of gene expression in the postnatal myogenesis period, growth restriction in utero led to a down regulation of myogenic factors, which delayed the expression of signals that induces skeletal muscle myogenesis (PAX7, MYOD, MYOG, MYF5 and DES). Taken together, the muscle morphofunctional aspects described and their ontogenetic regulation define the possible molecular origins of the notorious damage to the postnatal musculature development in IUGR pigs.