Relationship of Skeletal Muscle Development and Growth to Breast Muscle Myopathies: A Review Author(s): Sandra G. Velleman Source: Avian Diseases, 59(4):525-531. Published By: American Association of Avian Pathologists DOI: http://dx.doi.org/10.1637/11223-063015-Review.1 URL: http://www.bioone.org/doi/full/10.1637/11223-063015-Review.1
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AVIAN DISEASES 59:525–531, 2015
Relationship of Skeletal Muscle Development and Growth to Breast Muscle Myopathies: A Review Sandra G. VellemanA Department of Animal Sciences, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691 Received 1 July 2015; Accepted 12 August 2015; Published ahead of print 13 August 2015 SUMMARY. Selection in meat-type birds has focused on growth rate, muscling, and feed conversion. These strategies have made substantial improvements but have affected muscle structure, repair mechanisms, and meat quality, especially in the breast muscle. The increase in muscle fiber diameters has reduced available connective tissue spacing, reduced blood supply, and altered muscle metabolism in the breast muscle. These changes have increased muscle fiber degeneration and necrosis but have limited muscle repair mechanisms mediated by the adult myoblast (satellite cell) population of cells, likely resulting in the onset of myopathies. This review focuses on muscle growth mechanisms and how changes in the cellular development of the breast muscle may be associated with breast muscle myopathies occurring in meat-type birds. RESUMEN. Relacio´n entre el desarrollo y crecimiento del mu´sculo esquele´tico y miopatı´as del mu´sculo de la pechuga: Estudio Recapitulativo. La seleccio´n de aves para carne se ha centrado en la tasa de crecimiento, en el desarrollo de la musculatura y en la conversio´n alimenticia. Estas estrategias han hecho mejoras sustanciales pero han afectado la estructura del mu´sculo, los mecanismos de reparacio´n y la calidad de la carne, especialmente del mu´sculo de la pechuga. El aumento de los dia´metros de las fibras musculares ha reducido el espacio disponible para el tejido conectivo, ha reducido el suministro de sangre y ha alterado el metabolismo muscular del el mu´sculo de la pechuga. Estos cambios han aumentado los procesos de degeneracio´n y necrosis de las fibras musculares y han limitado los mecanismos de reparacio´n del mu´sculo, que son mediados por la poblacio´n de mioblastos adultos (ce´lulas sate´lites), lo que probablemente resulta en la aparicio´n de miopatı´as. Esta revisio´n se centra en los mecanismos del crecimiento muscular y en como los cambios en el desarrollo celular del mu´sculo de la pechuga pueden estar asociados con miopatı´as musculares que se presentan en las aves productoras de carne. Key words: angiogenesis, muscle, myopathy, satellite cell Abbreviations: FG 5 fast-twitch, glycolytic; FOG 5 fast-twitch, oxidative/glycolytic; PSE 5 pale, soft, and exudative; SO 5 slow-twitch, oxidative
Consumer demand for meat with low fat and high protein levels has led to a significant increase in the consumption of poultry meat, especially the breast. To meet this consumer demand, commercial broilers and turkeys have been selected for rapid growth, the accretion of breast muscle mass, conformation of the muscle, and feed conversion. However, myopathies affecting breast meat quality in terms of visual appearance, water-holding capacity, textural properties, and fat content have been reported in both broilers and turkeys, predominantly in fast-growing lines. The focus of this review paper is to determine how changes in the cellular development of the breast muscle may be associated with breast muscle myopathies occurring in meat-type birds. Avian skeletal muscle growth is comprised of distinct and precisely regulated periods of embryonic and posthatch muscle growth. Embryonic muscle is derived from mesodermal cells in the somites located on both sides of the notochord. The mesodermal cells migrate from the somites to appropriate sites for muscle formation and will proliferate. The embryonic myoblasts fuse to form multinucleated primary muscle fibers. After primary myofiber formation, secondary muscle fibers form adjacent to the primary myofibers. This stepwise formation of muscle fiber structure is necessary to ensure proper muscle fiber orientation and function. In birds as well as mammals, muscle fiber formation is complete at the time of hatch or birth (35). The embryonic myoblast development is accomplished through hyperplasia, which leads to the formation of multinucleated muscle fibers; myoblasts are withdrawn from the cell A
Corresponding author. E-mail: [email protected]
cycle and no longer participate in muscle growth. Thus, muscle growth after hatch is dependent upon another cellular source of nuclei not derived from the embryonic myoblasts. In 1961, Mauro (21) reported the presence of cells that were located between the muscle sarcolemma and basement membrane. Mauro termed these cells “satellite cells” because of their peripheral muscle fiber location (21). The satellite cells mediate all posthatch growth of existing muscle fibers by fusing with and donating their nuclei increasing protein synthesis potential (23, 37). Thus, posthatch muscle growth results in the enlargement or hypertrophy of existing muscle fibers. Satellite cells are most active in the late-term embryo or immediately posthatch, and their ability to proliferate rapidly declines after hatch (9). During the growth phase of muscle fiber enlargement (hypertrophy), the satellite cells proliferate and add nuclei to the muscle fibers formed during embryogenesis. Satellite cells withdraw from the cell cycle posthatch and remain quiescent. Upon being stressed by factors resulting in muscle damage, satellite cells are reactivated, undergo proliferation and differentiation, and undergo fusion with existing myofibers or synthesize new myofibers, thereby regenerating the damaged muscle (13). Quiescent satellite cells can also be activated by exercise.
SATELLITE CELLS ARE MULTIPOTENTIAL STEM CELLS
Satellite cells are a multipotential mesenchymal stem cell population with plasticity to commit to myogenesis or can undergo alternative differentiation programs such as osteogenesis or adipogenesis (2,32). Satellite cells are also referred to as adult myoblasts.
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As such, satellite cells can be induced to follow other cellular lineages when they are most active immediately after hatch. In vivo studies reported by Velleman et al. (40,41,42) demonstrated that feed restrictions the first week posthatch alter the expression of genes required for muscle satellite cell proliferation and differentiation, increase necrosis, and increase the formation of extensive intramuscular fat depots characteristic of “marbling” in the breast muscle. Moving the restriction to the second week posthatch eliminated these changes. In some species (e.g., beef and swine) these types of in vivo changes have been associated with preadipocytes and may or may not directly involve the satellite cells (4). To date, preadipocytes have not been reported in chicken and turkey breast muscle. Fat is primarily contained in the fat pads under the skin, and the breast muscle is a nonmarbled low-fat meat as a result of a general absence of intramuscular fat within the muscle fiber bundles and connective tissue perimysial spacing. In support of the in vivo results suggesting the conversion of satellite cells to an adipogenic lineage, Powell et al. (28,29), using isolated chicken pectoralis major satellite cells, and Harthan et al. (10), with turkey pectoralis major satellite cells devoid of other cell types, showed that satellite cell fate, proliferation, and differentiation characteristics are affected by a nutrient restriction and are capable of expressing adipogenic specific genes. Thus, environmental conditions, including handling efficiency during the period of maximal satellite cell activity immediately posthatch, may impact long-term performance of the bird, including both the muscle fibrillar structure and muscle weight. In addition to satellite cells being a multipotential stem cell population, satellite cells are also heterogeneous in nature based upon the fiber type of the muscle they are derived from and the dynamic expression of cell surface markers. Thus, differences in satellite cell type populations can affect the ability of satellite cells to proliferate and differentiate during muscle growth and regeneration. In general, there are three predominant muscle fiber types: 1) slowtwitch, oxidative (SO), type I or red fiber; 2) fast-twitch, glycolytic (FG), type IIB or white fiber; and 3) fast-twitch, oxidative/glycolytic (FOG), type IIA or intermediate fiber (1). The fiber type of a muscle is dependent upon the type of motion required, and satellite cells, in general, are fiber-type specific. Type I fibers have a higher aerobic capacity and increased blood supply for prolonged activity. Type I fibers oxidize glucose and glycogen through glycolysis and the tricarboxylic acid cycle as well as oxidize fatty acids by b-oxidation. In contrast, type IIB fibers are composed of glycolytic fibers, which metabolize glycogen and glucose to lactate and have lower blood supply. The pectoralis major muscle of domestic chickens and turkeys is mostly composed of type IIB fibers. Pale breast meat in broilers is considered a defect and is predominantly found in lines selected for increased breast muscle yield. According to Dransfield and Sosnicki (6) with increased growth rate, there is a higher proportion of a type IIB fiber or white fibers, which predispose the muscle to the pale defect. The breast muscles are the most economically valuable muscles in commercial poultry in terms of consumer preference in the United States, and due to their anaerobic metabolism, are more prone to myopathies affecting the value of the breast meat. The remainder of this review will focus on breast muscle structure. MORPHOLOGICAL STRUCTURE OF MUSCLE
Selection for muscle growth can be based on the period of hyperplasia and/or hypertrophy. Selection for the number of muscle fibers occurs during the embryonic phase of development, and thus
Fig. 1. Representative image showing turkey pectoralis major muscle structure with well-defined myofibers (F), perimysial (P) and endomysial (*) connective tissue spacing. Capillaries are highlighted by the arrows. Scale bar 5 100 mm.
selection for muscle development is usually based on posthatch muscle mass accretion through hypertrophy and muscle conformation. Selection for hypertrophy can result in muscle fibers that are three to five times larger in cross-sectional area (6). Frequently, larger fiber diameters are referred to as giant fibers, and often these larger diameter fibers will remain in a severely contracted state (hypercontracted). Muscle structure is characterized by the formation of muscle fiber bundles (Fig. 1). The number of fibers in a fiber bundle can range between 50 and 300 fibers, and the size of the individual fibers can vary. Each muscle fiber is separated by a connective tissue layer called the endomysium, and the muscle fiber bundles are separated by the perimysial connective tissue layer. The connective tissue layers are joined together at the myotendinous junction, including the epimysium, which surrounds and separates individual muscles. The interconnection of the epimysium, perimysium, and endomysium provides a strong structural support for muscles, and these connective tissue layers contain, for example, water-holding molecules like the large proteoglycans, structural support collagens, growth factors, and capillaries. Alterations to the morphological structure of the muscle ultimately affect meat quality, since meat quality is a reflection of the morphological structure and cell biology of the muscle. EFFECT OF INCREASED MUSCLE FIBER DIAMETER ON MUSCLE DAMAGE AND BREAST MUSCLE MYOPATHIES
Selection for increased muscling that favors muscle fiber hypertrophy has resulted in muscle fibers and fiber bundles that occupy areas originally maintained by the endomysial and perimysial connective tissue layers, respectively. Wilson et al. (43) compared breast muscle characteristics in turkey lines with various growth rates. More degenerating muscle fibers as reflected by higher plasma creatine kinase concentrations were found in rapidly growing lines compared with slower growing lines. The increased plasma levels of creatine kinase are reflective of a disruption of the integrity of the muscle fibers, since creatine kinase is usually just found within the muscle fiber. Fig. 2 shows breast muscle morphological structure from a turkey selected for only 16-wk body weight with extensive fiber degeneration and almost a complete absence of perimysial and endomysial connective tissue spacing. Distinct muscle fiber bundle organization is also absent. The reduction in available connective
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Fig. 2. Representative image of a degenerating turkey pectoralis major muscle. Scale bar 5 100 mm.
tissue spacing due to increased muscle fiber hypertrophy often associated with selection for rapid growth was described by Wilson et al. (43) as the creation of muscles that have outgrown their life support systems resulting in muscle fiber damage. In growth-selected birds, the breast muscle frequently has reduced endomysial and perimysial connective tissue spacing (38,43), which limits the available space for capillaries and hence reduces the amount of lactic acid removed from the muscle. A reduction in the number of capillaries surrounding degenerating or necrotic areas has been reported in hypertrophied breast muscle (36). The glycolytic mode of respiration found in poultry breast muscle results in the formation of lactic acid. Lactic acid is predominantly removed by the circulatory system and converted into glycogen by the liver (3). Turkeys selected for increased muscle have increased anaerobic respiration levels (44), which result in higher lactic acid concentration in the breast muscle and decreased pH. A reduction in the amount of capillaries further decreases pH through the retention of lactic acid. Increased concentration of lactic acid will enhance the muscle damage process and may be involved in myopathies affecting both broilers and turkeys. In pale, soft, and exudative (PSE) meat, for example, the meat when cooked has a soft texture, poor meat binding, poor juiciness due to reduced water-holding capacity, and increased yield loss. Birds prone to PSE have an accelerated decline in muscle pH that occurs with rigor mortis. The low pH coincides with the carcass still being warm, leading to the denaturation of muscle proteins (27). The physiological pH in live birds may be low because of muscle fiber degeneration and retained lactic acid. RNAseq analysis showed the turkey with PSE involves abnormalities in calcium homeostatis, actin cytoskeleton structure, and carbohydrate metabolism (18,19). Areas of the muscle undergoing degeneration or necrosis can evoke satellite cell-mediated repair mechanisms to regenerate the muscle. Satellite cells are a dynamic population of cells that have the ability to mediate muscle growth through hypertrophy and also regenerate muscle in response to damage. During the regeneration of muscle, as in hypertrophy, the satellite cells are activated and re-enter the cell cycle, proliferate, and differentiate. The area surrounding the satellite cells, also termed the muscle stem cell niche, must contain the appropriate environment to active the satellite cells. Recent findings in systems other than poultry have shown a required presence of vascular cells in the muscle stem cell niche, and that signaling is required between satellite cells and vascular cells for
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satellite cell activation (5,31). The regeneration of skeletal muscle has been shown to require both the temporal and spatial coordination of myogenic and angiogenic events (7,30). Satellite cells proliferate close to capillaries, and regeneration of muscle requires vascularization of the tissue as both myogenesis and angiogenesis occur simultaneously (5,16,31). In adult humans, satellite cells are located within 21 mm of capillaries (5). If sufficient vascularization is not present, fibrosis of the muscle occurs (20). Angiogenesis is also stimulated by satellite cells, most likely through soluble-growth factors like hepatocyte growth factor, vascular endothelial growth factor, and fibroblast growth factor produced by the satellite cells (31). If selection for larger diameter fibers is altering the vascular nature of the stem cell niche, regeneration of the breast muscle in response to damage is suppressed, resulting in the development of myopathies. For example, the deep pectoral myopathy also known as green muscle disease is a degenerative myopathy deep in the breast muscle usually in the pectoralis minor or supracocracoidus muscles. Deep pectoral myopathy occurs in birds selected for breast muscle growth. It results in degeneration and complete necrosis, with the muscle becoming green in color at late stages of the myopathy. Blood supply to the areas of the breast muscle prone to deep pectoral myopathy is limited as a result of the occlusion of blood vessels by the size of the muscle (34). Satellite cell-mediated regeneration of the deep areas of the breast muscle is inhibited by the lack of blood supply needed for satellite cell activity. Fast-twitch muscle fibers like the pectoralis major muscle have fewer satellite cells than slow-twitch oxidative muscles typical of those found in the leg or thigh (8,17). Furthermore, vascular endothelial cells promote the proliferation of muscle cells through the secretion of growth factors (5). Satellite cells are extremely responsive to the stimulatory or inhibitory effects of growth factors like fibroblast growth factor 2, insulin-like growth factor I, hepatocyte growth factor, platelet-derived growth factor BB, and vascular endothelial cell growth factor (22). In fast-growing commercial broiler lines from two separate commercial poultry breeding companies, myofiber size and capillary density were evaluated to market age in the pectoralis major muscle (14). Myofiber diameter was found to increase with age through hypertrophy, and capillary density adjacent to the myofiber was marginalized increasing microischemia of the muscle. Taken together, these studies suggest that the pectoralis major muscle of birds with reduced vasculature, satellite cell activity is suppressed, leading to the degeneration and necrosis of the muscle. Since slow-twitch oxidative muscles have more capillaries due to being an aerobic muscle, these muscles can be less prone to rapid-growth-induced degeneration. Satellite cell-mediated muscle regeneration in response to damage is a precisely regulated process ultimately resulting in the repair or creation of new myofibers. Muscle fiber degeneration is initiated by the disruption of the myofiber plasma membrane (sarcolemma) and results in increased plasma levels of creatine kinase. After the initial degeneration, the myofiber begins to undergo necrosis due to increased influx of calcium from the sarcoplasmic reticulum and activation of the calcium-dependent protease calpain. An immune response is simultaneously activated with muscle fiber necrosis (26). The immune response starts with neutrophils and is then followed by macrophage invasion to the area of damage to phagocytize the cellular debris. The inflammatory cytokines tumor necrosis factor a and interleukin 1 are also expressed during this time. After degeneration, myofiber regeneration is initiated by the activation, proliferation, and differentiation of the satellite cells. The satellite cells can fuse with existing muscle fibers or fuse to each other to form new muscle fibers. The regenerated muscle fibers should be
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Fig. 3. Representative image of a broiler pectoralis major muscle with the wooden breast myopathy. C 5 collagen; F 5 fat cells; M 5 macrophages; and N 5 myofiber necrosis. Scale bar 5 100 mm.
functional and morphologically similar to the muscle fibers prior to degeneration in terms of diameter. The wooden breast condition is a myopathy affecting the breast muscle in fast-growing commercial broiler lines. Wooden breast– affected birds are phenotypically detected by palpation of the breast area, with affected birds having a very hard breast muscle with a wood-like phenotype. The phenotypic hardness of the breast muscle in wooden breast–affected birds is associated with the breast muscle being pale in color and often having a white-striped appearance (33). Furthermore, the wooden breast myopathy to date has only been reported in the breast muscle in predominantly fastgrowing broiler lines (33). The morphological structure of wooden breast condition found in broiler affected muscle is characterized by extensive necrosis of existing muscle fibers, invasion of macrophages, and fibrosis (Fig. 3). With fibrosis, muscle is replaced with connective tissue, and in the case of wooden breast the collagen is extensively cross-linked, which will result in the wood-like texture of the muscle (39). Collagen cross-linking is a progressive process and associated with the toughening of meat. Muscles with more crosslinking are tougher, and the meat product becomes less desirable to consumers. Since a high proportion of necrotic or hypercontracted myofibers exists with the wooden breast myopathy, activation of regeneration mechanisms to repair damaged muscle fibers will stimulate both proliferation and differentiation of satellite cells. Velleman and Clark (39) demonstrated that in wooden breast–affected muscles satellite cell-mediated regeneration is occurring as indicated by the elevated expression of myogenic transcriptional regulatory factors regulating satellite cell proliferation and differentiation. Despite the activation of satellite cell-mediated repair mechanisms, muscle fiber regeneration results in muscle fibers that are significantly smaller in diameter than unaffected muscle fibers. Although not understood at the present time, muscle fiber regeneration does not result in a morphologically similar muscle fiber with respect to diameter with the wooden breast myopathy. It is possible that increased muscle size due to growth selection in fast-growing lines has led to a reduction in vascularization of the wooden breast–affected muscles, thereby reducing muscle fiber regeneration, since satellite cell activity is directly associated with angiogenesis (5,16,31). The white striping condition in broilers is phenotypically observable in boneless skinless breast muscle fillets as white striations
Fig. 4. Morphology of pectoralis major muscle fat depots at 42 days of age in the (A) control full-fed, and (B) week 2 feed-restricted chicks. The arrows highlight the fat depots in both the control and feed-restricted pectoralis major muscle. Scale bar 5 50 mm. [Figure reproduced from Velleman et al. (40).]
running parallel to the muscle fibers (15). An emerging question is whether the white striping and wooden breast are the same or a similar myopathy. At this point, it is premature to guess whether they are the same or similar myopathies. Both of these are complex conditions affecting the breast muscle and not acceptable to consumers in terms of breast meat quality causing necrosis, fibrosis, and lipidosis (15,33,39). The cellular mechanisms resulting in these myopathies are not known. Velleman and Clark (39) suggested that the wooden breast myopathy may not have only one mechanistic cause resulting in the fibrotic changes in breast muscle morphological structure but that these changes can vary between different broiler lines. CONVERSION OF SATELLITE CELLS FROM A MYOGENIC CELL FATE TO AN ADIPOGENIC LINEAGE
Although satellite cells have been traditionally described as myogenic precursors committed to growth and regeneration of muscle after hatch, research has shown that satellite cells are a multipotential mesenchymal stem cell population with plasticity to commit to myogenesis or alternative differentiation programs such as osteogenesis or adipogenesis (2,32). Powell et al. (28,29), using isolated chicken pectoralis major satellite cells, and Harthan et al. (10), with turkey pectoralis major satellite cells, showed that satellite cell fate, proliferation, and differentiation characteristics are affected by nutritional conditions. Satellite cell mitotic activity is maximal during the first week posthatch (9,24). Halevy et al. (9) used 2-day feed deprivation to measure the effect of limiting feed on breast muscle growth and satellite cell proliferation. The timing of the 2-day feed
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Fig. 5. Morphological structure of the pectoralis major muscle from day 8 through day 30 of age in the control, and week 2 feed-restricted chicks. A, C, E, and G are representative images of the control pectoralis major muscle at days 8, 14, 22, and 30. B, D, F, and H are representative images of the week 2 feed-restricted pectoralis major muscle at days 8, 14, 22, and 30 of age. The arrow highlights endomysial connective spacing, and the asterisk indicates perimysial connective tissue spacing. Scale bar 5 50 mm. [Figure reproduced from Velleman et al. (41).]
deprivation in relation to hatch was critical in its effect on satellite cellmediated posthatch muscle growth. The closer the period of fasting was to hatch up to 4 days, satellite cell mitotic activity and number was reduced, and breast muscle weight never reached levels of the full fed birds at market age. Depriving feed from 4 to 6 days of age resulted in unaltered satellite cell mitotic activity and breast muscle weight at processing.
Feed restrictions are commonly used by the industry, as well as inadvertent delays in newly hatched chicks and poults obtaining feed during handling after hatch. In vivo studies by Velleman et al. (40,41) demonstrated that feed restrictions the first week posthatch altered the expression of genes required for breast muscle satellite cell proliferation and differentiation, and increased myofiber necrosis and the formation of intramuscular fat depots characteristic of
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“marbling” occurred (Fig. 4). Moving the restriction to the second week posthatch after the period of maximal satellite cell activity eliminated the changes in muscle-specific gene expression, increase in myofiber necrosis, and intramuscular fat deposition (Fig. 5). CONCLUSION
Growth rate, feed conversion, and muscle mass accretion have improved in commercial meat birds (11,12,25). However, in recent years myopathies affecting meat quality have arisen and may be caused by changes in the musculoskeletal system associated with selection for increased growth. Muscle growth occurs in two distinct phases: hyperplasia and hypertrophy. Hyperplasia occurs embryonically and increases the muscle cell number, whereas hypertrophy posthatch increases the muscle fiber size. Selection for breast muscle mass accretion has largely been based on hypertrophy, resulting in increased muscle fiber diameters, reduction in available connective tissue spacing, and increased myofiber degeneration. These changes to the morphological structure of the breast muscle limit blood supply, water-holding molecules, and other factors necessary for the survival of the muscle, and they affect meat quality. Management strategies need to be developed to include the morphological structure and cell biology of the breast muscle as part of selection processes to reduce the occurrence of myopathies. REFERENCES 1. Allen, R. E., and D. E. Goll. Cellular and developmental biology of skeletal muscle as related to muscle growth. In: Biology of growth of domestic animals, C. G. Scanes, ed. Iowa State Press, Ames, IA. pp. 148–169. 2003. 2. Asakura, A., M. Komaki, and M. Rudnicki. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation 68:245–253. 2001. 3. Bangsbo, J., P. D. Gollnick, T. E. Grahm, and B. Saltin. Substrates for muscle glycogen synthesis in recovery from intense exercise in man. J. Physiol. 434:423–440. 1991. 4. Bi, P., and S. Kuang. Stem cell niche and postnatal muscle growth. J. Anim. Sci. 90:924–935. 2012. 5. Christov, C., F. Chre´tien, R. Abou-Khalil, G. Bassez, G. Vallet, F.-J. Authier, Y. Bassaglia, V. Shinin, S. Tajbakhsh, B. Chazaud, and R. K. Gherardi. Muscle satellite cells and endothelial cells: close neighbors and privileged partners. Mol Biol. Cell 18:1397–1409. 2007. 6. Dransfield, E., and A. A. Sosnicki. Relationship between muscle growth and poultry meat quality. Poult. Sci. 78:743–746. 1999. 7. Flann, K. L., C. R. Rathbone, L. C. Cole, X. Liu, R. E. Allen, and R. P. Rhoads. Hypoxia simultaneously alters satellite cell-mediated angiogenesis and hepatocyte growth factor expression. J. Cell. Physiol. 229:572–579. 2014. 8. Gibson, M. C., and E. Schultz. The distribution of satellite cells and their relationship to specific fiber types in soleus and extensor digitorum longus muscles. Anat. Rec. 202:329–337. 1982. 9. Halevy, O., A. Geyra, M. Barak, Z. Uni, and D. Sklan. Early posthatch starvation decreases satellite cell proliferation and skeletal muscle growth in chicks. J. Nutr. 130:459–463. 2000. 10. Harthan, L. B., D. C. McFarland, and S. G. Velleman. The effect of nutritional status and myogenic satellite cell age on turkey satellite cell proliferation, differentiation, and expression of myogenic transcriptional regulatory factors and heparan sulfate proteoglycans syndecan-4 and glypican-1. Poult. Sci. 93:174–186. 2014. 11. Haverstein, G. B., P. R. Ferket, S. E. Scheidler, and B. Larson. Growth, livability, and feed conversion of 1957 vs 1991 broilers when fed “typical” 1957 and 1991 broiler diets. Poult. Sci. 73:1785–1794. 1994. 12. Haverstein, G. B., P. R. Ferket, S. E. Scheidler, and D. V. Rives. Carcass composition and yield of 1991 vs 1957 broilers when fed “typical” 1957 and 1991 broiler diets. Poult. Sci. 73:1795–1804. 1994.
13. Hawke, T. J., and D. J. Garry. Myogenic satellite cells: physiology to molecular biology. J. Appl. Physiol. 91:534–551. 2001. 14. Joiner, K. S., G. A. Hamlin, A. R. Lien, and S. F. Bilgili. Evaluation of capillary and myofiber density in the pectoralis major muscles of rapidly growing high-yield broiler chickens during increased heat stress. Avian Dis. 58:377–382. 2014. 15. Kuttappan, V. A., H. L. Shivaprasad, D. P. Shaw, B. A. Valentine, B. M. Hargis, F. D. Clark, S. R. McKee, and C. M. Owens. Pathological changes associated with white striping in broiler breast muscles. Poult. Sci. 92:331–338. 2013. 16. Luque, E., J. Pena, P. Martin, I. Jimena, and R. Vaamonde. Capillary supply during development of individual regenerating muscle fibers. Anat. Histol. Embryol. 24:87–89. 1995. 17. Mackey, A. L., M. Kjaer, N. Charifi, J. Henriksson, J. Bojsen-Moller, L. Holm, and F. Kadi. Assessment of satellite cell number and activity status in human skeletal muscle biopsies. Muscle Nerve 40:455–465. 2009. 18. Maliala, Y., K. M. Carr, C. W. Ernst, S. G. Velleman, K. M. Reed, and G. M. Strasburg. Deep transcriptome sequencing reveals differences in global gene expression between normal and pale, soft, and exudative (PSE) turkey meat. J. Anat. Sci. 92:1250–1260. 2014. 19. Maliala, Y., R. J. Tempelman, K. R. B. Sporer, C. W. Ernst, S. G. Velleman, K. M. Reed, and G. M. Strasburg. Microarray analysis of differential gene expression between normal and pale, soft and exudative turkey meat. Poult. Sci. 92:1621–1633. 2013. 20. Markley, J. M., J. A. Faulkner, and B. M. Carlson. Regeneration of skeletal muscle after grafting in monkeys. Plast. Reconstr. Surg. 62:415–422. 1978. 21. Mauro, A. Satellite cell of skeletal muscle fibers. J. Biophys. Biochem. Cytol. 9:493–495. 1961. 22. McFarland, D. C. Influence of growth factors on poultry myogenic satellite cells. Poult. Sci. 78:747–758. 1999. 23. Moss, F. P., and C. P. LeBlond. Satellite cells are the source of nuclei in muscles of growing rats. Anat. Rec. 170:421–435. 1971. 24. Mozdziak, P. E., T. J. Walsh, and D. W. McCoy. The effect of early posthatch nutrition on satellite cell mitotic activity. Poult. Sci. 81:1703–1708. 2002. 25. Nestor, K. E., M. G. McCartney, and N. Bachev. Relative contribution of genetics and environment to turkey improvement. Poult. Sci. 48:1944–1949. 1969. 26. Orimo, S., E. Hiyamuta, K. Arahata, and H. Sugita. Analysis of inflammatory cells and complement C3 in bupivacaine-induced myonecrosis. Muscle and Nerve 14:515–520. 1991. 27. Owens, C. M., E. M. Hirschler, S. R. McKee, R. Martinez-Dawson, and A. R. Sams. The characterization of pale, soft, exudative turkey meat in a commercial plant. Poult. Sci. 79:553–558. 2000. 28. Powell, D. J., D. C. McFarland, A. J. Cowieson, W. I. Muir, and S. G. Velleman. The effect of nutritional status on myogenic satellite cell proliferation and differentiation. Poult. Sci. 92:2163–2173. 2013. 29. Powell, D. J., D. C. McFarland, A. J. Cowieson, W. I. Muir, and S. G. Velleman. The effect of nutritional status and muscle fiber type on myogenic satellite cell fate and apoptosis. Poult. Sci. 93:163–173. 2014. 30. Rhoads, R. P., K. L. Flann, T. R. Cardinal, C. R. Rathbone, X. Liu, and R. E. Allen. Satellite cells isolated from aged or dystrophic muscle exhibit a reduced capacity to promote angiogenesis in vitro. Biochem. Biophys. Res. Comm. 440:399–404. 2013. 31. Rhoads, R. P., R. M. Johnson, C. R. Rathbone, X. Liu, C. TemmGrove, S. M. Sheehan, J. B. Hoying, and R. E. Allen. Satellite cell-mediated angiogenesis in vitro coincides with a functional hypoxia-inducible factor pathway. Am. J. Physiol. Cell Physiol. 296:C1321–C1328. 2009. 32. Shefer, G., M. Wleklinski-Lee, and Z. Yablonka-Reuveni. Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway. J. Cell Sci. 117:5393–5404. 2004. 33. Sihvo, H.-K., K. Immonen, and E. Puolanne. Myodegeneration with fibrosis and regeneration in the pectoralis major muscle of broilers. Vet. Pathol. 51:619–623. 2013. 34. Siller, W. G. Deep pectoral myopathy: a penalty of successful selection for muscle growth. Poult. Sci. 64:1591–1595. 1985. 35. Smith, J. H. Relation of body size to muscle cell size and number in the chicken. Poult. Sci. 42:283–290. 1963.
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36. Sosnicki, A. A., and B. W. Wilson. Pathology of turkey skeletal muscle: implications for the poultry industry. Food Structure 10:317–326. 1991. 37. Stockdale, F. E., and H. Holtzer. DNA synthesis and myogenesis. Exp. Cell Res. 24:508–520. 1961. 38. Velleman, S. G., J. W. Anderson, C. S. Coy, and K. E. Nestor. Effect of selection for growth rate on muscle damage during turkey breast muscle development. Poult. Sci. 82:1069–1074. 2003. 39. Velleman, S. G., and D. L. Clark. Effect of the wooden breast myopathy on fibrosis and myogenic gene expression. Avian Dis. 59: 410–418. 2015. 40. Velleman, S. G., C. S. Coy, and D. A. Emmerson. Effect of timing of posthatch feed restrictions on the deposition of fat during broiler breast muscle development. Poult. Sci. 93:1–6. 2014.
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41. Velleman, S. G., C. S. Coy, and D. A. Emmerson. Effect if the timing of posthatch feed restrictions on broiler muscle development and muscle transcriptional regulatory factor gene expression. Poult. Sci. 93:1484–1494. 2014. 42. Velleman, S. G., K. E. Nestor, C. S. Coy, I. Harford, and N. B. Anthony. Effect of posthatch feed restriction on broiler breast muscle development and muscle transcriptional regulatory factor gene and heparan sulfate proteoglycan expression. Int. J. Poult. Sci. 9:417–425. 2010. 43. Wilson, B. W., P. S. Nieberg, and R. J. Buhr. Turkey muscle growth and focal myopathy. Poult. Sci. 69:1553–1562. 1990. 44. Yost, J. K., P. B. Kenney, S. D. Slider, R. W. Russell, and J. Killefer. Influence of selection for breast muscle mass on myosin isoform composition and metabolism of deep pectoralis muscles of male and female turkeys. Poult. Sci. 81:911–917. 2002.
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AVIAN DISEASES 59:525–531, 2015
Relationship of Skeletal Muscle Development and Growth to Breast Muscle Myopathies: A Review Sandra G. VellemanA Department of Animal Sciences, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691 Received 1 July 2015; Accepted 12 August 2015; Published ahead of print 13 August 2015 SUMMARY. Selection in meat-type birds has focused on growth rate, muscling, and feed conversion. These strategies have made substantial improvements but have affected muscle structure, repair mechanisms, and meat quality, especially in the breast muscle. The increase in muscle fiber diameters has reduced available connective tissue spacing, reduced blood supply, and altered muscle metabolism in the breast muscle. These changes have increased muscle fiber degeneration and necrosis but have limited muscle repair mechanisms mediated by the adult myoblast (satellite cell) population of cells, likely resulting in the onset of myopathies. This review focuses on muscle growth mechanisms and how changes in the cellular development of the breast muscle may be associated with breast muscle myopathies occurring in meat-type birds. RESUMEN. Relacio´n entre el desarrollo y crecimiento del mu´sculo esquele´tico y miopatı´as del mu´sculo de la pechuga: Estudio Recapitulativo. La seleccio´n de aves para carne se ha centrado en la tasa de crecimiento, en el desarrollo de la musculatura y en la conversio´n alimenticia. Estas estrategias han hecho mejoras sustanciales pero han afectado la estructura del mu´sculo, los mecanismos de reparacio´n y la calidad de la carne, especialmente del mu´sculo de la pechuga. El aumento de los dia´metros de las fibras musculares ha reducido el espacio disponible para el tejido conectivo, ha reducido el suministro de sangre y ha alterado el metabolismo muscular del el mu´sculo de la pechuga. Estos cambios han aumentado los procesos de degeneracio´n y necrosis de las fibras musculares y han limitado los mecanismos de reparacio´n del mu´sculo, que son mediados por la poblacio´n de mioblastos adultos (ce´lulas sate´lites), lo que probablemente resulta en la aparicio´n de miopatı´as. Esta revisio´n se centra en los mecanismos del crecimiento muscular y en como los cambios en el desarrollo celular del mu´sculo de la pechuga pueden estar asociados con miopatı´as musculares que se presentan en las aves productoras de carne. Key words: angiogenesis, muscle, myopathy, satellite cell Abbreviations: FG 5 fast-twitch, glycolytic; FOG 5 fast-twitch, oxidative/glycolytic; PSE 5 pale, soft, and exudative; SO 5 slow-twitch, oxidative
Consumer demand for meat with low fat and high protein levels has led to a significant increase in the consumption of poultry meat, especially the breast. To meet this consumer demand, commercial broilers and turkeys have been selected for rapid growth, the accretion of breast muscle mass, conformation of the muscle, and feed conversion. However, myopathies affecting breast meat quality in terms of visual appearance, water-holding capacity, textural properties, and fat content have been reported in both broilers and turkeys, predominantly in fast-growing lines. The focus of this review paper is to determine how changes in the cellular development of the breast muscle may be associated with breast muscle myopathies occurring in meat-type birds. Avian skeletal muscle growth is comprised of distinct and precisely regulated periods of embryonic and posthatch muscle growth. Embryonic muscle is derived from mesodermal cells in the somites located on both sides of the notochord. The mesodermal cells migrate from the somites to appropriate sites for muscle formation and will proliferate. The embryonic myoblasts fuse to form multinucleated primary muscle fibers. After primary myofiber formation, secondary muscle fibers form adjacent to the primary myofibers. This stepwise formation of muscle fiber structure is necessary to ensure proper muscle fiber orientation and function. In birds as well as mammals, muscle fiber formation is complete at the time of hatch or birth (35). The embryonic myoblast development is accomplished through hyperplasia, which leads to the formation of multinucleated muscle fibers; myoblasts are withdrawn from the cell A
Corresponding author. E-mail: [email protected]
cycle and no longer participate in muscle growth. Thus, muscle growth after hatch is dependent upon another cellular source of nuclei not derived from the embryonic myoblasts. In 1961, Mauro (21) reported the presence of cells that were located between the muscle sarcolemma and basement membrane. Mauro termed these cells “satellite cells” because of their peripheral muscle fiber location (21). The satellite cells mediate all posthatch growth of existing muscle fibers by fusing with and donating their nuclei increasing protein synthesis potential (23, 37). Thus, posthatch muscle growth results in the enlargement or hypertrophy of existing muscle fibers. Satellite cells are most active in the late-term embryo or immediately posthatch, and their ability to proliferate rapidly declines after hatch (9). During the growth phase of muscle fiber enlargement (hypertrophy), the satellite cells proliferate and add nuclei to the muscle fibers formed during embryogenesis. Satellite cells withdraw from the cell cycle posthatch and remain quiescent. Upon being stressed by factors resulting in muscle damage, satellite cells are reactivated, undergo proliferation and differentiation, and undergo fusion with existing myofibers or synthesize new myofibers, thereby regenerating the damaged muscle (13). Quiescent satellite cells can also be activated by exercise.
SATELLITE CELLS ARE MULTIPOTENTIAL STEM CELLS
Satellite cells are a multipotential mesenchymal stem cell population with plasticity to commit to myogenesis or can undergo alternative differentiation programs such as osteogenesis or adipogenesis (2,32). Satellite cells are also referred to as adult myoblasts.
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As such, satellite cells can be induced to follow other cellular lineages when they are most active immediately after hatch. In vivo studies reported by Velleman et al. (40,41,42) demonstrated that feed restrictions the first week posthatch alter the expression of genes required for muscle satellite cell proliferation and differentiation, increase necrosis, and increase the formation of extensive intramuscular fat depots characteristic of “marbling” in the breast muscle. Moving the restriction to the second week posthatch eliminated these changes. In some species (e.g., beef and swine) these types of in vivo changes have been associated with preadipocytes and may or may not directly involve the satellite cells (4). To date, preadipocytes have not been reported in chicken and turkey breast muscle. Fat is primarily contained in the fat pads under the skin, and the breast muscle is a nonmarbled low-fat meat as a result of a general absence of intramuscular fat within the muscle fiber bundles and connective tissue perimysial spacing. In support of the in vivo results suggesting the conversion of satellite cells to an adipogenic lineage, Powell et al. (28,29), using isolated chicken pectoralis major satellite cells, and Harthan et al. (10), with turkey pectoralis major satellite cells devoid of other cell types, showed that satellite cell fate, proliferation, and differentiation characteristics are affected by a nutrient restriction and are capable of expressing adipogenic specific genes. Thus, environmental conditions, including handling efficiency during the period of maximal satellite cell activity immediately posthatch, may impact long-term performance of the bird, including both the muscle fibrillar structure and muscle weight. In addition to satellite cells being a multipotential stem cell population, satellite cells are also heterogeneous in nature based upon the fiber type of the muscle they are derived from and the dynamic expression of cell surface markers. Thus, differences in satellite cell type populations can affect the ability of satellite cells to proliferate and differentiate during muscle growth and regeneration. In general, there are three predominant muscle fiber types: 1) slowtwitch, oxidative (SO), type I or red fiber; 2) fast-twitch, glycolytic (FG), type IIB or white fiber; and 3) fast-twitch, oxidative/glycolytic (FOG), type IIA or intermediate fiber (1). The fiber type of a muscle is dependent upon the type of motion required, and satellite cells, in general, are fiber-type specific. Type I fibers have a higher aerobic capacity and increased blood supply for prolonged activity. Type I fibers oxidize glucose and glycogen through glycolysis and the tricarboxylic acid cycle as well as oxidize fatty acids by b-oxidation. In contrast, type IIB fibers are composed of glycolytic fibers, which metabolize glycogen and glucose to lactate and have lower blood supply. The pectoralis major muscle of domestic chickens and turkeys is mostly composed of type IIB fibers. Pale breast meat in broilers is considered a defect and is predominantly found in lines selected for increased breast muscle yield. According to Dransfield and Sosnicki (6) with increased growth rate, there is a higher proportion of a type IIB fiber or white fibers, which predispose the muscle to the pale defect. The breast muscles are the most economically valuable muscles in commercial poultry in terms of consumer preference in the United States, and due to their anaerobic metabolism, are more prone to myopathies affecting the value of the breast meat. The remainder of this review will focus on breast muscle structure. MORPHOLOGICAL STRUCTURE OF MUSCLE
Selection for muscle growth can be based on the period of hyperplasia and/or hypertrophy. Selection for the number of muscle fibers occurs during the embryonic phase of development, and thus
Fig. 1. Representative image showing turkey pectoralis major muscle structure with well-defined myofibers (F), perimysial (P) and endomysial (*) connective tissue spacing. Capillaries are highlighted by the arrows. Scale bar 5 100 mm.
selection for muscle development is usually based on posthatch muscle mass accretion through hypertrophy and muscle conformation. Selection for hypertrophy can result in muscle fibers that are three to five times larger in cross-sectional area (6). Frequently, larger fiber diameters are referred to as giant fibers, and often these larger diameter fibers will remain in a severely contracted state (hypercontracted). Muscle structure is characterized by the formation of muscle fiber bundles (Fig. 1). The number of fibers in a fiber bundle can range between 50 and 300 fibers, and the size of the individual fibers can vary. Each muscle fiber is separated by a connective tissue layer called the endomysium, and the muscle fiber bundles are separated by the perimysial connective tissue layer. The connective tissue layers are joined together at the myotendinous junction, including the epimysium, which surrounds and separates individual muscles. The interconnection of the epimysium, perimysium, and endomysium provides a strong structural support for muscles, and these connective tissue layers contain, for example, water-holding molecules like the large proteoglycans, structural support collagens, growth factors, and capillaries. Alterations to the morphological structure of the muscle ultimately affect meat quality, since meat quality is a reflection of the morphological structure and cell biology of the muscle. EFFECT OF INCREASED MUSCLE FIBER DIAMETER ON MUSCLE DAMAGE AND BREAST MUSCLE MYOPATHIES
Selection for increased muscling that favors muscle fiber hypertrophy has resulted in muscle fibers and fiber bundles that occupy areas originally maintained by the endomysial and perimysial connective tissue layers, respectively. Wilson et al. (43) compared breast muscle characteristics in turkey lines with various growth rates. More degenerating muscle fibers as reflected by higher plasma creatine kinase concentrations were found in rapidly growing lines compared with slower growing lines. The increased plasma levels of creatine kinase are reflective of a disruption of the integrity of the muscle fibers, since creatine kinase is usually just found within the muscle fiber. Fig. 2 shows breast muscle morphological structure from a turkey selected for only 16-wk body weight with extensive fiber degeneration and almost a complete absence of perimysial and endomysial connective tissue spacing. Distinct muscle fiber bundle organization is also absent. The reduction in available connective
Skeletal muscle growth and development
Fig. 2. Representative image of a degenerating turkey pectoralis major muscle. Scale bar 5 100 mm.
tissue spacing due to increased muscle fiber hypertrophy often associated with selection for rapid growth was described by Wilson et al. (43) as the creation of muscles that have outgrown their life support systems resulting in muscle fiber damage. In growth-selected birds, the breast muscle frequently has reduced endomysial and perimysial connective tissue spacing (38,43), which limits the available space for capillaries and hence reduces the amount of lactic acid removed from the muscle. A reduction in the number of capillaries surrounding degenerating or necrotic areas has been reported in hypertrophied breast muscle (36). The glycolytic mode of respiration found in poultry breast muscle results in the formation of lactic acid. Lactic acid is predominantly removed by the circulatory system and converted into glycogen by the liver (3). Turkeys selected for increased muscle have increased anaerobic respiration levels (44), which result in higher lactic acid concentration in the breast muscle and decreased pH. A reduction in the amount of capillaries further decreases pH through the retention of lactic acid. Increased concentration of lactic acid will enhance the muscle damage process and may be involved in myopathies affecting both broilers and turkeys. In pale, soft, and exudative (PSE) meat, for example, the meat when cooked has a soft texture, poor meat binding, poor juiciness due to reduced water-holding capacity, and increased yield loss. Birds prone to PSE have an accelerated decline in muscle pH that occurs with rigor mortis. The low pH coincides with the carcass still being warm, leading to the denaturation of muscle proteins (27). The physiological pH in live birds may be low because of muscle fiber degeneration and retained lactic acid. RNAseq analysis showed the turkey with PSE involves abnormalities in calcium homeostatis, actin cytoskeleton structure, and carbohydrate metabolism (18,19). Areas of the muscle undergoing degeneration or necrosis can evoke satellite cell-mediated repair mechanisms to regenerate the muscle. Satellite cells are a dynamic population of cells that have the ability to mediate muscle growth through hypertrophy and also regenerate muscle in response to damage. During the regeneration of muscle, as in hypertrophy, the satellite cells are activated and re-enter the cell cycle, proliferate, and differentiate. The area surrounding the satellite cells, also termed the muscle stem cell niche, must contain the appropriate environment to active the satellite cells. Recent findings in systems other than poultry have shown a required presence of vascular cells in the muscle stem cell niche, and that signaling is required between satellite cells and vascular cells for
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satellite cell activation (5,31). The regeneration of skeletal muscle has been shown to require both the temporal and spatial coordination of myogenic and angiogenic events (7,30). Satellite cells proliferate close to capillaries, and regeneration of muscle requires vascularization of the tissue as both myogenesis and angiogenesis occur simultaneously (5,16,31). In adult humans, satellite cells are located within 21 mm of capillaries (5). If sufficient vascularization is not present, fibrosis of the muscle occurs (20). Angiogenesis is also stimulated by satellite cells, most likely through soluble-growth factors like hepatocyte growth factor, vascular endothelial growth factor, and fibroblast growth factor produced by the satellite cells (31). If selection for larger diameter fibers is altering the vascular nature of the stem cell niche, regeneration of the breast muscle in response to damage is suppressed, resulting in the development of myopathies. For example, the deep pectoral myopathy also known as green muscle disease is a degenerative myopathy deep in the breast muscle usually in the pectoralis minor or supracocracoidus muscles. Deep pectoral myopathy occurs in birds selected for breast muscle growth. It results in degeneration and complete necrosis, with the muscle becoming green in color at late stages of the myopathy. Blood supply to the areas of the breast muscle prone to deep pectoral myopathy is limited as a result of the occlusion of blood vessels by the size of the muscle (34). Satellite cell-mediated regeneration of the deep areas of the breast muscle is inhibited by the lack of blood supply needed for satellite cell activity. Fast-twitch muscle fibers like the pectoralis major muscle have fewer satellite cells than slow-twitch oxidative muscles typical of those found in the leg or thigh (8,17). Furthermore, vascular endothelial cells promote the proliferation of muscle cells through the secretion of growth factors (5). Satellite cells are extremely responsive to the stimulatory or inhibitory effects of growth factors like fibroblast growth factor 2, insulin-like growth factor I, hepatocyte growth factor, platelet-derived growth factor BB, and vascular endothelial cell growth factor (22). In fast-growing commercial broiler lines from two separate commercial poultry breeding companies, myofiber size and capillary density were evaluated to market age in the pectoralis major muscle (14). Myofiber diameter was found to increase with age through hypertrophy, and capillary density adjacent to the myofiber was marginalized increasing microischemia of the muscle. Taken together, these studies suggest that the pectoralis major muscle of birds with reduced vasculature, satellite cell activity is suppressed, leading to the degeneration and necrosis of the muscle. Since slow-twitch oxidative muscles have more capillaries due to being an aerobic muscle, these muscles can be less prone to rapid-growth-induced degeneration. Satellite cell-mediated muscle regeneration in response to damage is a precisely regulated process ultimately resulting in the repair or creation of new myofibers. Muscle fiber degeneration is initiated by the disruption of the myofiber plasma membrane (sarcolemma) and results in increased plasma levels of creatine kinase. After the initial degeneration, the myofiber begins to undergo necrosis due to increased influx of calcium from the sarcoplasmic reticulum and activation of the calcium-dependent protease calpain. An immune response is simultaneously activated with muscle fiber necrosis (26). The immune response starts with neutrophils and is then followed by macrophage invasion to the area of damage to phagocytize the cellular debris. The inflammatory cytokines tumor necrosis factor a and interleukin 1 are also expressed during this time. After degeneration, myofiber regeneration is initiated by the activation, proliferation, and differentiation of the satellite cells. The satellite cells can fuse with existing muscle fibers or fuse to each other to form new muscle fibers. The regenerated muscle fibers should be
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Fig. 3. Representative image of a broiler pectoralis major muscle with the wooden breast myopathy. C 5 collagen; F 5 fat cells; M 5 macrophages; and N 5 myofiber necrosis. Scale bar 5 100 mm.
functional and morphologically similar to the muscle fibers prior to degeneration in terms of diameter. The wooden breast condition is a myopathy affecting the breast muscle in fast-growing commercial broiler lines. Wooden breast– affected birds are phenotypically detected by palpation of the breast area, with affected birds having a very hard breast muscle with a wood-like phenotype. The phenotypic hardness of the breast muscle in wooden breast–affected birds is associated with the breast muscle being pale in color and often having a white-striped appearance (33). Furthermore, the wooden breast myopathy to date has only been reported in the breast muscle in predominantly fastgrowing broiler lines (33). The morphological structure of wooden breast condition found in broiler affected muscle is characterized by extensive necrosis of existing muscle fibers, invasion of macrophages, and fibrosis (Fig. 3). With fibrosis, muscle is replaced with connective tissue, and in the case of wooden breast the collagen is extensively cross-linked, which will result in the wood-like texture of the muscle (39). Collagen cross-linking is a progressive process and associated with the toughening of meat. Muscles with more crosslinking are tougher, and the meat product becomes less desirable to consumers. Since a high proportion of necrotic or hypercontracted myofibers exists with the wooden breast myopathy, activation of regeneration mechanisms to repair damaged muscle fibers will stimulate both proliferation and differentiation of satellite cells. Velleman and Clark (39) demonstrated that in wooden breast–affected muscles satellite cell-mediated regeneration is occurring as indicated by the elevated expression of myogenic transcriptional regulatory factors regulating satellite cell proliferation and differentiation. Despite the activation of satellite cell-mediated repair mechanisms, muscle fiber regeneration results in muscle fibers that are significantly smaller in diameter than unaffected muscle fibers. Although not understood at the present time, muscle fiber regeneration does not result in a morphologically similar muscle fiber with respect to diameter with the wooden breast myopathy. It is possible that increased muscle size due to growth selection in fast-growing lines has led to a reduction in vascularization of the wooden breast–affected muscles, thereby reducing muscle fiber regeneration, since satellite cell activity is directly associated with angiogenesis (5,16,31). The white striping condition in broilers is phenotypically observable in boneless skinless breast muscle fillets as white striations
Fig. 4. Morphology of pectoralis major muscle fat depots at 42 days of age in the (A) control full-fed, and (B) week 2 feed-restricted chicks. The arrows highlight the fat depots in both the control and feed-restricted pectoralis major muscle. Scale bar 5 50 mm. [Figure reproduced from Velleman et al. (40).]
running parallel to the muscle fibers (15). An emerging question is whether the white striping and wooden breast are the same or a similar myopathy. At this point, it is premature to guess whether they are the same or similar myopathies. Both of these are complex conditions affecting the breast muscle and not acceptable to consumers in terms of breast meat quality causing necrosis, fibrosis, and lipidosis (15,33,39). The cellular mechanisms resulting in these myopathies are not known. Velleman and Clark (39) suggested that the wooden breast myopathy may not have only one mechanistic cause resulting in the fibrotic changes in breast muscle morphological structure but that these changes can vary between different broiler lines. CONVERSION OF SATELLITE CELLS FROM A MYOGENIC CELL FATE TO AN ADIPOGENIC LINEAGE
Although satellite cells have been traditionally described as myogenic precursors committed to growth and regeneration of muscle after hatch, research has shown that satellite cells are a multipotential mesenchymal stem cell population with plasticity to commit to myogenesis or alternative differentiation programs such as osteogenesis or adipogenesis (2,32). Powell et al. (28,29), using isolated chicken pectoralis major satellite cells, and Harthan et al. (10), with turkey pectoralis major satellite cells, showed that satellite cell fate, proliferation, and differentiation characteristics are affected by nutritional conditions. Satellite cell mitotic activity is maximal during the first week posthatch (9,24). Halevy et al. (9) used 2-day feed deprivation to measure the effect of limiting feed on breast muscle growth and satellite cell proliferation. The timing of the 2-day feed
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Fig. 5. Morphological structure of the pectoralis major muscle from day 8 through day 30 of age in the control, and week 2 feed-restricted chicks. A, C, E, and G are representative images of the control pectoralis major muscle at days 8, 14, 22, and 30. B, D, F, and H are representative images of the week 2 feed-restricted pectoralis major muscle at days 8, 14, 22, and 30 of age. The arrow highlights endomysial connective spacing, and the asterisk indicates perimysial connective tissue spacing. Scale bar 5 50 mm. [Figure reproduced from Velleman et al. (41).]
deprivation in relation to hatch was critical in its effect on satellite cellmediated posthatch muscle growth. The closer the period of fasting was to hatch up to 4 days, satellite cell mitotic activity and number was reduced, and breast muscle weight never reached levels of the full fed birds at market age. Depriving feed from 4 to 6 days of age resulted in unaltered satellite cell mitotic activity and breast muscle weight at processing.
Feed restrictions are commonly used by the industry, as well as inadvertent delays in newly hatched chicks and poults obtaining feed during handling after hatch. In vivo studies by Velleman et al. (40,41) demonstrated that feed restrictions the first week posthatch altered the expression of genes required for breast muscle satellite cell proliferation and differentiation, and increased myofiber necrosis and the formation of intramuscular fat depots characteristic of
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“marbling” occurred (Fig. 4). Moving the restriction to the second week posthatch after the period of maximal satellite cell activity eliminated the changes in muscle-specific gene expression, increase in myofiber necrosis, and intramuscular fat deposition (Fig. 5). CONCLUSION
Growth rate, feed conversion, and muscle mass accretion have improved in commercial meat birds (11,12,25). However, in recent years myopathies affecting meat quality have arisen and may be caused by changes in the musculoskeletal system associated with selection for increased growth. Muscle growth occurs in two distinct phases: hyperplasia and hypertrophy. Hyperplasia occurs embryonically and increases the muscle cell number, whereas hypertrophy posthatch increases the muscle fiber size. Selection for breast muscle mass accretion has largely been based on hypertrophy, resulting in increased muscle fiber diameters, reduction in available connective tissue spacing, and increased myofiber degeneration. These changes to the morphological structure of the breast muscle limit blood supply, water-holding molecules, and other factors necessary for the survival of the muscle, and they affect meat quality. Management strategies need to be developed to include the morphological structure and cell biology of the breast muscle as part of selection processes to reduce the occurrence of myopathies. REFERENCES 1. Allen, R. E., and D. E. Goll. Cellular and developmental biology of skeletal muscle as related to muscle growth. In: Biology of growth of domestic animals, C. G. Scanes, ed. Iowa State Press, Ames, IA. pp. 148–169. 2003. 2. Asakura, A., M. Komaki, and M. Rudnicki. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation 68:245–253. 2001. 3. Bangsbo, J., P. D. Gollnick, T. E. Grahm, and B. Saltin. Substrates for muscle glycogen synthesis in recovery from intense exercise in man. J. Physiol. 434:423–440. 1991. 4. Bi, P., and S. Kuang. Stem cell niche and postnatal muscle growth. J. Anim. Sci. 90:924–935. 2012. 5. Christov, C., F. Chre´tien, R. Abou-Khalil, G. Bassez, G. Vallet, F.-J. Authier, Y. Bassaglia, V. Shinin, S. Tajbakhsh, B. Chazaud, and R. K. Gherardi. Muscle satellite cells and endothelial cells: close neighbors and privileged partners. Mol Biol. Cell 18:1397–1409. 2007. 6. Dransfield, E., and A. A. Sosnicki. Relationship between muscle growth and poultry meat quality. Poult. Sci. 78:743–746. 1999. 7. Flann, K. L., C. R. Rathbone, L. C. Cole, X. Liu, R. E. Allen, and R. P. Rhoads. Hypoxia simultaneously alters satellite cell-mediated angiogenesis and hepatocyte growth factor expression. J. Cell. Physiol. 229:572–579. 2014. 8. Gibson, M. C., and E. Schultz. The distribution of satellite cells and their relationship to specific fiber types in soleus and extensor digitorum longus muscles. Anat. Rec. 202:329–337. 1982. 9. Halevy, O., A. Geyra, M. Barak, Z. Uni, and D. Sklan. Early posthatch starvation decreases satellite cell proliferation and skeletal muscle growth in chicks. J. Nutr. 130:459–463. 2000. 10. Harthan, L. B., D. C. McFarland, and S. G. Velleman. The effect of nutritional status and myogenic satellite cell age on turkey satellite cell proliferation, differentiation, and expression of myogenic transcriptional regulatory factors and heparan sulfate proteoglycans syndecan-4 and glypican-1. Poult. Sci. 93:174–186. 2014. 11. Haverstein, G. B., P. R. Ferket, S. E. Scheidler, and B. Larson. Growth, livability, and feed conversion of 1957 vs 1991 broilers when fed “typical” 1957 and 1991 broiler diets. Poult. Sci. 73:1785–1794. 1994. 12. Haverstein, G. B., P. R. Ferket, S. E. Scheidler, and D. V. Rives. Carcass composition and yield of 1991 vs 1957 broilers when fed “typical” 1957 and 1991 broiler diets. Poult. Sci. 73:1795–1804. 1994.
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