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

Abstract

2728 Intrauterine growth restriction (IUGR) is a serious condition which impairs the 29 achievement of the fetus full growth potential and occurs in a natural and severe 30 manner in pigs. Knowledge on skeletal muscle morphofunctional phenotype and its 31 molecular regulation in IUGR pigs is important to understand postnatal muscle 32 development and may help the establishment of therapies to improve skeletal muscle 33 growth in those individuals. To investigate the impairment of skeletal muscle 34 postnatal development due to IUGR, we evaluated the histomorphometrical pattern 35 of the semitendinosus muscle, the Myosin Heavy Chain (embryonic, I, IIa, IIb and IIx 36 MyHC) fiber composition and the relative expression of genes related to myogenesis, 37 adipogenesis and growth during three specific periods: postnatal myogenesis 38 (newborn to 100 days of age), postnatal development (newborn to 150 days of age), 39 and hypertrophy (100 days to 150 days of age), comparing IUGR and normal birth 40 weight (NW) pigs. Growth restriction in utero affected muscle fiber diameter, total 41 fiber number and muscle cross sectional area which were smaller in IUGR pigs at 42 birth (P < 0.05). Even though the percentage of MyHC-I myofibers was higher in 43 IUGR females at birth (P < 0.05), in older gilts, a lower percentage of MyHC-IIx 44 isoform (P < 0.05) and the presence of emb-MyHC were also observed in that 45 experimental group. Regarding the pattern of gene expression in the postnatal 46 myogenesis period, growth restriction in utero led to a down regulation of myogenic 47 factors, which delayed the expression of signals that induces skeletal muscle 48 myogenesis (PAX7, MYOD, MYOG, MYF5 and DES). Taken together, the muscle 49 morphofunctional aspects described and their ontogenetic regulation define the 3 50 possible molecular origins of the notorious damage to the postnatal musculature 51 development in IUGR pigs.52 53 Key words: birth weight, IUGR, MyHC, myogenesis, skeletal muscle. 54 55 Introduction 56 Intrauterine growth restriction (IUGR) is defined as the impaired development 57 of the mammalian fetus, or its organs, preventing it from reaching its full growth 58 potential. This condition is characterized by low birth weight and is considered the 59 second cause of infant mortality in the world [1]. It is also associated to the 60 predisposition to certain chronic diseases (e.g. hypertension, obesity and diabetes) in 61 adulthood. The main cause of IUGR is an insufficiency of the placenta in distributing 62 enough nutrients and oxygen to the offspring [2]. 63 IUGR is a significant problem not only in human neonatology but also in swine 64 production. Breeding selection for increased litter size in this species has resulted in 65 increased number of small piglets at birth, in particular those affected by IUGR [3] [4] 66 [5]. In this species, growth restriction in utero is mainly caused by uterine crowding, 67 resulting in asymmetrical IUGR [6] [7]. Moreover, this condition may increase the risk 68 of neonatal morbidi...