Postnatal development of skeletal muscle in pigs with intrauterine growth restriction: morphofunctional phenotype and molecular mechanisms.

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 as a result of placental insufficiency. Reduced skeletal muscle mass in the fetus with IUGR persists into adulthood and may contribute to increased metabolic disease risk. To investigate skeletal muscle postnatal development, histomorphometrical patterns of the semitendinosus muscle, myosin heavy chain (MyHC; embryonic I, IIA, IIB and IIX isoforms) fiber composition and the relative expression of genes related to myogenesis, adipogenesis and growth during three specific periods: postnatal myogenesis (newborn to 100 days old), hypertrophy (100-150 days old), and postnatal development (newborn to 150 days old) were evaluated in female pigs with IUGR and normal birth weight (NW) female littermates. NW females presented higher body weights compared to their IUGR counterparts at all ages evaluated (P < 0.05). Moreover, growth restriction in utero affected the semitendinosus muscle weight, muscle fiber diameter, and muscle cross-sectional area, which were smaller in IUGR pigs at birth (P < 0.05). Notwithstanding the effects on muscle morphology, IUGR also affected muscle fiber composition, as the percentage of MyHC-I myofibers was higher at birth (P < 0.05), and, in 150-day-old gilts, a lower percentage of MyHC-IIX isoform (P < 0.05) and the presence of embryonic MyHC isoform were also observed. Regarding the pattern of gene expression in both the postnatal myogenesis and postnatal development periods, IUGR led to the downregulation of myogenic factors, which delayed skeletal muscle myogenesis (PAX7, MYOD, MYOG, MYF5 and DES). Altogether, growth restriction in utero affects muscle fiber number and size at birth and muscle fiber composition through the downregulation of myogenic factors, which determines the individual´s postnatal growth rate. This fact, associated with delayed myofiber development in growth-restricted animals, may affect meat quality characteristics in animal production. Hence, knowledge of the morphofunctional phenotype of the skeletal muscle throughout postnatal development in individuals with IUGR, and the mechanism that governs it, may provide a better understanding of the mechanisms that limit postnatal muscle growth, and help the establishment of potential strategies to improve muscle development and prevent the onset of later-life metabolic diseases.