{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:44:21Z","timestamp":1783392261583,"version":"3.54.6"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intrauterine growth restriction (IUGR) is linked to lifelong reductions in muscle mass due to intrinsic functional deficits in myoblasts, but the mechanisms underlying these deficits are not known. Our objective was to determine if the deficits were associated with changes in inflammatory and adrenergic regulation of IUGR myoblasts, as was previously observed in IUGR muscle. Primary myoblasts were isolated from IUGR fetal sheep produced by hyperthermia-induced placental insufficiency (PI-IUGR; n = 9) and their controls (n = 9) and from IUGR fetal sheep produced by maternofetal inflammation (MI-IUGR; n = 6) and their controls (n = 7). Proliferation rates were less (P &amp;lt; 0.05) for PI-IUGR myoblasts than their controls and were not affected by incubation with IL-6, TNF-\u03b1, norepinephrine, or insulin. I\u03baB kinase inhibition reduced (P &amp;lt; 0.05) proliferation of control myoblasts modestly in basal media but substantially in TNF-\u03b1-added media and reduced (P &amp;lt; 0.05) PI-IUGR myoblast proliferation substantially in basal and TNF-\u03b1-added media. Proliferation was greater (P &amp;lt; 0.05) for MI-IUGR myoblasts than their controls and was not affected by incubation with TNF-\u03b1. Insulin increased (P &amp;lt; 0.05) proliferation in both MI-IUGR and control myoblasts. After 72-h differentiation, fewer (P &amp;lt; 0.05) PI-IUGR myoblasts were myogenin+ than controls in basal and IL-6 added media but not TNF-\u03b1-added media. Fewer (P &amp;lt; 0.05) PI-IUGR myoblasts were desmin+ than controls in basal media only. Incubation with norepinephrine did not affect myogenin+ or desmin+ percentages, but insulin increased (P &amp;lt; 0.05) both markers in control and PI-IUGR myoblasts. After 96-h differentiation, fewer (P &amp;lt; 0.05) MI-IUGR myoblasts were myogenin+ and desmin+ than controls regardless of media, although TNF-\u03b1 reduced (P &amp;lt; 0.05) desmin+ myoblasts for both groups. Differentiated PI-IUGR myoblasts had greater (P &amp;lt; 0.05) TNFR1, ULK2, and TNF-\u03b1-stimulated TLR4 gene expression, and PI-IUGR semitendinosus muscle had greater (P &amp;lt; 0.05) TNFR1 and IL6 gene expression, greater (P &amp;lt; 0.05) c-Fos protein, and less (P &amp;lt; 0.05) I\u03baB\u03b1 protein. Differentiated MI-IUGR myoblasts had greater (P &amp;lt; 0.05) TNFR1 and IL6R gene expression, tended to have greater (P = 0.07) ULK2 gene expression, and had greater (P &amp;lt; 0.05) \u03b2-catenin protein and TNF-\u03b1-stimulated phosphorylation of NF\u03baB. We conclude that these enriched components of TNF-\u03b1\/TNFR1\/NF\u03baB and other inflammatory pathways in IUGR myoblasts contribute to their dysfunction and help explain impaired muscle growth in the IUGR fetus.<\/jats:p>","DOI":"10.1093\/jas\/skac145","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:19:59Z","timestamp":1659313199000},"source":"Crossref","is-referenced-by-count":13,"title":["Primary myoblasts from intrauterine growth-restricted fetal sheep exhibit intrinsic dysfunction of proliferation and differentiation that coincides with enrichment of inflammatory cytokine signaling pathways"],"prefix":"10.1093","volume":"100","author":[{"given":"Robert J","family":"Posont","sequence":"first","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln , Lincoln, NE 68583 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah S","family":"Most","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln , Lincoln, NE 68583 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin N","family":"Cadaret","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln , Lincoln, NE 68583 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen S","family":"Marks-Nelson","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln , Lincoln, NE 68583 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin A","family":"Beede","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln , Lincoln, NE 68583 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5851-0439","authenticated-orcid":false,"given":"Sean W","family":"Limesand","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, The University of Arizona , Tucson, AZ 65721 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ty B","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln , Lincoln, NE 68583 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-8555","authenticated-orcid":false,"given":"Jessica L","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln , Lincoln, NE 68583 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin T","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln , Lincoln, NE 68583 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"2022080100193928600_CIT0001","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2527\/jas1979.491115x","article-title":"Cellular aspects of muscle growth - myogenic cell-proliferation","volume":"49","author":"Allen","year":"1979","journal-title":"J. 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