{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T20:05:59Z","timestamp":1774641959344,"version":"3.50.1"},"reference-count":84,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2014,6,2]],"date-time":"2014-06-02T00:00:00Z","timestamp":1401667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK084842"],"award-info":[{"award-number":["R01 DK084842"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Food and Agriculture, USDA","award":["2012-67012-19855"],"award-info":[{"award-number":["2012-67012-19855"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,7,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>To investigate loss of skeletal muscle mass in intrauterine growth\u2010restricted (IUGR) fetuses near term, which may result from myoblast dysfunction, we examined semitendinosus myofibre and myoblast morphology in placental insufficiency\u2010induced IUGR sheep fetuses; we also isolated and cultured IUGR fetal myoblasts to determine whether reduced rates of proliferation were due to intrinsic cellular defects or extrinsic factors associated with serum.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using tests for myogenin and pax7 to identify differentiated and undifferentiated fetal myoblasts, respectively, we found that myofibre area and percentage of myogenin\u2010positive nuclei were less in IUGR fetal semitendinosus muscles than in controls, but myofibre density and percentage of pax7\u2010positive nuclei were not different.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The percentage of pax7\u2010positive cells that expressed proliferating cellular nuclear antigen was less in IUGR semitendinosus muscles than in controls, while in myoblasts isolated from fetal sheep and replicated and differentiated in culture, IUGR fetal myoblasts proliferated at slower rates than control myoblasts, under identical culture conditions, but the ability to differentiate was similar between treatments.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Media supplemented with IUGR serum decreased replication rates in both IUGR and control myoblasts compared to media supplemented with control fetal serum.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings show that myoblasts proliferate at slower rates in IUGR fetuses due to a combination of intrinsic cellular characteristics and extrinsic serum factors; the intrinsic defects may explain reduced skeletal muscle mass observed in IUGR newborn children and adults.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Intrauterine growth restriction (IUGR) reduces skeletal muscle mass in fetuses and offspring. Our objective was to determine whether myoblast dysfunction due to intrinsic cellular deficiencies or serum factors reduces myofibre hypertrophy in IUGR fetal sheep. At 134\u00a0days, IUGR fetuses weighed 67% less (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05) than controls and had smaller (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05) carcasses and semitendinosus myofibre areas. IUGR semitendinosus muscles had similar percentages of pax7\u2010positive nuclei and pax7 mRNA but lower (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05) percentages of myogenin\u2010positive nuclei (7\u00a0\u00b1\u00a02% and 13\u00a0\u00b1\u00a02%), less myoD and myogenin mRNA, and fewer (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05) proliferating myoblasts (PNCA\u2010positive\u2013pax7\u2010positive) than controls (44\u00a0\u00b1\u00a02% <jats:italic>vs<\/jats:italic>. 52\u00a0\u00b1\u00a01%). Primary myoblasts were isolated from hindlimb muscles, and after 3\u00a0days in growth media (20% fetal bovine serum, FBS), myoblasts from IUGR fetuses had 34% fewer (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05) myoD\u2010positive cells than controls and replicated 20% less (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05) during a 2\u00a0h BrdU pulse. IUGR myoblasts also replicated less (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05) than controls during a BrdU pulse after 3\u00a0days in media containing 10% control or IUGR fetal sheep serum (FSS). Both myoblast types replicated less (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05) with IUGR FSS\u2010supplemented media compared to control FSS\u2010supplemented media. In differentiation\u2010promoting media (2% FBS), IUGR and control myoblasts had similar percentages of myogenin\u2010positive nuclei after 5\u00a0days and formed similar\u2010sized myotubes after 7\u00a0days. We conclude that intrinsic cellular deficiencies in IUGR myoblasts and factors in IUGR serum diminish myoblast proliferation and myofibre size in IUGR fetuses, but intrinsic myoblast deficiencies do not affect differentiation. Furthermore, the persistent reduction in IUGR myoblast replication shows adaptive deficiencies that explain poor muscle growth in IUGR newborn offspring.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.272591","type":"journal-article","created":{"date-parts":[[2014,5,24]],"date-time":"2014-05-24T04:19:41Z","timestamp":1400905181000},"page":"3113-3125","source":"Crossref","is-referenced-by-count":71,"title":["Myoblasts from intrauterine growth\u2010restricted sheep fetuses exhibit intrinsic deficiencies in proliferation that contribute to smaller semitendinosus myofibres"],"prefix":"10.1113","volume":"592","author":[{"given":"Dustin T.","family":"Yates","sequence":"first","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences The University of Arizona  Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek S.","family":"Clarke","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences The University of Arizona  Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoni R.","family":"Macko","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences The University of Arizona  Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences The University of Arizona  Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie A.","family":"Shelton","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences The University of Arizona  Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Nearing","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences The University of Arizona  Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald E.","family":"Allen","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences The University of Arizona  Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Rhoads","sequence":"additional","affiliation":[{"name":"Department of Animal and Poultry Sciences Virginia Tech  Blacksburg VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean W.","family":"Limesand","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences The University of Arizona  Tucson AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,6,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/80.1.199"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199910)22:10<1350::AID-MUS3>3.0.CO;2-8"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041380213"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.2527\/jas1985.6061571x","article-title":"Effect of insulin and linoleic acid on satellite cell differentiation","volume":"60","author":"Allen RE","year":"1985","journal-title":"J\u00a0Anim Sci"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas1979.491115x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041490323"},{"key":"e_1_2_6_8_1","first-page":"155","volume-title":"Methods in Cell Biology","author":"Allen RE","year":"1997"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00399095"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0562"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-131870"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-014-9376-y"},{"key":"e_1_2_6_13_1","volume-title":"Comprehensive Physiology","author":"Blaauw B","year":"2011"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2012.11.004"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1670429"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00059.2012"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.192310"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2012.011375"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2008.04.009"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0072"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2006-743"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e32831cef9f"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1955"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00340.2004"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000242364.78002.71"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.3.5.628"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.2527\/2005.83112564x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.1.267"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.03.017"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200907037"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00193.2009"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1017\/S175173110700050X"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.2527\/2000.78150x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD99054"},{"key":"e_1_2_6_35_1","first-page":"253","article-title":"Muscle growth in two genetically different lines of swine","volume":"40","author":"Harbison SA","year":"1976","journal-title":"Growth"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-005-0454-1"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1769009"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2007.01812.x"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003738"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(90)90088-R"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13224-012-0190-4"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/82.5.980"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.1980"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/111.10.1823"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206410109"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00494.2009"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-09-0867"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.1.129"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90832.2008"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00435.2012"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00459.2007"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0900"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174413000093"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01737997"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1797009"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.173161"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2003.00871.x"},{"key":"e_1_2_6_58_1","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.2527\/jas1987.6451419x","article-title":"Effects of maternal undernutrition during early pregnancy on growth, muscle cellularity, fiber type and carcass composition in lambs","volume":"64","author":"Nordby DJ","year":"1987","journal-title":"J\u00a0Anim Sci"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1669-7"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.06.045"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/337570a0"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)07244-9"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2002.0792"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2001.0757"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00391.2008"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041590222"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas1977.445759x"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22127"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1789"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-2-3"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas1978.4661597x"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2000.279.1.E83"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1037-5"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.2007.00208.x"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.47.254.652"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01737996"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(65)90009-6"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2010.0349"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2007-0473"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/740408"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/631038"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0803612"},{"key":"e_1_2_6_83_1","first-page":"19","article-title":"[Insulin promotes proliferation of skeletal myoblast cells through PI3K\/Akt and MEK\/ERK pathways in rats]","volume":"65","author":"Yu H","year":"2013","journal-title":"Sheng Li Xue Bao"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02908"},{"key":"e_1_2_6_85_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.112110"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2014.272591","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2014.272591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T16:18:30Z","timestamp":1696004310000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2014.272591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,2]]},"references-count":84,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2014,7,15]]}},"alternative-id":["10.1113\/jphysiol.2014.272591"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2014.272591","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,2]]}}}