{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:26:57Z","timestamp":1785403617888,"version":"3.56.0"},"posted":{"date-parts":[[2025,6,17]]},"group-title":"Developmental Biology","reference-count":105,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Research Council","award":["336306"],"award-info":[{"award-number":["336306"]}]},{"name":"European Research Council","award":["101124603"],"award-info":[{"award-number":["101124603"]}]},{"DOI":"10.13039\/501100025294","name":"Research Ireland","doi-asserted-by":"crossref","award":["23\/US\/3923"],"award-info":[{"award-number":["23\/US\/3923"]}],"id":[{"id":"10.13039\/501100025294","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R01-HD113596"],"award-info":[{"award-number":["R01-HD113596"]}]},{"award":["P30-AR069619"],"award-info":[{"award-number":["P30-AR069619"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["K12GM081259"],"award-info":[{"award-number":["K12GM081259"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"award":["15-48571"],"award-info":[{"award-number":["15-48571"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Center for Undergraduate Research and Fellowships"],"award-info":[{"award-number":["Center for Undergraduate Research and Fellowships"]}],"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Fetal movements exert mechanical forces that shape the developing skeleton. Conditions that impair fetal movements can cause skeletal defects, but interventions are limited. Here, we show that maternal wheel running exercise regulates fetal skeletal development in mice. In wild-type fetuses, maternal exercise stimulated joint and bone morphogenesis. We reasoned that these effects occurred through either indirect maternofetal communication or direct mechanical stimulation of the fetus. Maternal exercise did not alter placental measures of nutrient transport. However, in the Splotch-delayed (Sp\n                  <jats:sup>d<\/jats:sup>\n                  ) mouse model of fetal akinesia, which features intact maternofetal communication but lacks fetal movements, maternal exercise substantially rescued fetal akinesia-impaired joint and bone development and prevented disuse-induced resorption of the deltoid tuberosity. Further, direct mechanical stimulation of Sp\n                  <jats:sup>d<\/jats:sup>\n                  limbs explanted from systemic factors similarly stimulated joint morphogenesis. Together, these findings identify maternal exercise as a regulator of fetal skeletal development, providing a platform for studying skeletal developmental mechanobiology and suggesting potential therapeutic applications for fetuses with impaired movement.\n                <\/jats:p>","DOI":"10.1101\/2025.06.17.660083","type":"posted-content","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T15:10:15Z","timestamp":1750173015000},"source":"Crossref","is-referenced-by-count":0,"title":["Maternal exercise rescues fetal akinesia-impaired joint and bone development"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-5743","authenticated-orcid":false,"given":"Christopher J.","family":"Panebianco","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-762X","authenticated-orcid":false,"given":"Nidal","family":"Khatib","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK"},{"name":"School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2210-9077","authenticated-orcid":false,"given":"Devin C.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0686-5343","authenticated-orcid":false,"given":"Maha","family":"Essaidi","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6206-3184","authenticated-orcid":false,"given":"Saima","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8708-112X","authenticated-orcid":false,"given":"Nathaniel A.","family":"Dyment","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-8904","authenticated-orcid":false,"given":"Rebecca A.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Center for Research, Reproduction and Women\u2019s Health, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Divison of Neonatology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-3025","authenticated-orcid":false,"given":"Joel D.","family":"Boerckel","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9083-6279","authenticated-orcid":false,"given":"Niamh C.","family":"Nowlan","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Imperial College London, London, UK"},{"name":"School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland"},{"name":"UCD Conway Institute, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041203505779000_2025.06.17.660083v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(96)13141-4"},{"key":"2026041203505779000_2025.06.17.660083v1.2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.105536"},{"key":"2026041203505779000_2025.06.17.660083v1.3","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v029a01"},{"key":"2026041203505779000_2025.06.17.660083v1.4","doi-asserted-by":"crossref","unstructured":"Verbruggen, S. W. et al. Stresses and strains on the human fetal skeleton during development. J R Soc Interface 15, (2018).","DOI":"10.1098\/rsif.2017.0593"},{"key":"2026041203505779000_2025.06.17.660083v1.5","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-023-03665-0"},{"key":"2026041203505779000_2025.06.17.660083v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2008.10.003"},{"key":"2026041203505779000_2025.06.17.660083v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2008.11.001"},{"key":"2026041203505779000_2025.06.17.660083v1.8","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/179827"},{"key":"2026041203505779000_2025.06.17.660083v1.9","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4011"},{"key":"2026041203505779000_2025.06.17.660083v1.10","first-page":"40","article-title":"Arthrogryposis: A Review and Update","volume":"91","year":"2009","journal-title":"Journal of Bone and Joint Surgery"},{"key":"2026041203505779000_2025.06.17.660083v1.11","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36395"},{"key":"2026041203505779000_2025.06.17.660083v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/BF02553275"},{"key":"2026041203505779000_2025.06.17.660083v1.13","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420420102"},{"key":"2026041203505779000_2025.06.17.660083v1.14","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420450215"},{"key":"2026041203505779000_2025.06.17.660083v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420460111"},{"key":"2026041203505779000_2025.06.17.660083v1.16","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5505"},{"key":"2026041203505779000_2025.06.17.660083v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62151"},{"key":"2026041203505779000_2025.06.17.660083v1.18","doi-asserted-by":"publisher","DOI":"10.1086\/physzool.13.4.30151585"},{"key":"2026041203505779000_2025.06.17.660083v1.19","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.3.1.9"},{"key":"2026041203505779000_2025.06.17.660083v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(66)90022-4"},{"key":"2026041203505779000_2025.06.17.660083v1.21","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1052060105"},{"key":"2026041203505779000_2025.06.17.660083v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9629(92)90237-K"},{"key":"2026041203505779000_2025.06.17.660083v1.23","first-page":"159","article-title":"The effects of paralysis on skeletal development in the chick embryo. I. General effects","volume":"177","year":"1991","journal-title":"J Anat"},{"key":"2026041203505779000_2025.06.17.660083v1.24","first-page":"169","article-title":"The effects of paralysis on skeletal development in the chick embryo. II. Effects on histogenesis of the tibia","volume":"177","year":"1991","journal-title":"J Anat"},{"key":"2026041203505779000_2025.06.17.660083v1.25","doi-asserted-by":"crossref","unstructured":"Rolfe, R. A. , Scanlon O\u2019Callaghan, D. & Murphy, P . Joint development recovery on resumption of embryonic movement following paralysis. Dis Model Mech 14, (2021).","DOI":"10.1242\/dmm.048913"},{"key":"2026041203505779000_2025.06.17.660083v1.26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017526"},{"key":"2026041203505779000_2025.06.17.660083v1.27","doi-asserted-by":"publisher","DOI":"10.1159\/000145566"},{"key":"2026041203505779000_2025.06.17.660083v1.28","first-page":"127","article-title":"Differential effects of embryonic immobilization on the development of fibrocartilaginous skeletal elements","volume":"37","year":"2000","journal-title":"J Rehabil Res Dev"},{"key":"2026041203505779000_2025.06.17.660083v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(65)90038-2"},{"key":"2026041203505779000_2025.06.17.660083v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(65)90039-4"},{"key":"2026041203505779000_2025.06.17.660083v1.31","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.134.2.375"},{"key":"2026041203505779000_2025.06.17.660083v1.32","first-page":"153","article-title":"The Splotch mutation interferes with muscle development in the limbs","volume":"187","year":"1993","journal-title":"Anat Embryol (Berl)"},{"key":"2026041203505779000_2025.06.17.660083v1.33","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.3.603"},{"key":"2026041203505779000_2025.06.17.660083v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80189-0"},{"key":"2026041203505779000_2025.06.17.660083v1.35","doi-asserted-by":"publisher","DOI":"10.1007\/s00427-005-0024-9"},{"key":"2026041203505779000_2025.06.17.660083v1.36","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.20184"},{"key":"2026041203505779000_2025.06.17.660083v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2010.08.039"},{"key":"2026041203505779000_2025.06.17.660083v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.11.026"},{"key":"2026041203505779000_2025.06.17.660083v1.39","doi-asserted-by":"crossref","unstructured":"Rolfe, R. A. et al. Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways. BMC Genomics 15, 48 (2014).","DOI":"10.1186\/1471-2164-15-48"},{"key":"2026041203505779000_2025.06.17.660083v1.40","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-38215-4_4"},{"key":"2026041203505779000_2025.06.17.660083v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.07.026"},{"key":"2026041203505779000_2025.06.17.660083v1.42","doi-asserted-by":"publisher","DOI":"10.1242\/dev.063768"},{"key":"2026041203505779000_2025.06.17.660083v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.115849"},{"key":"2026041203505779000_2025.06.17.660083v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.10.010"},{"key":"2026041203505779000_2025.06.17.660083v1.45","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v011a07"},{"key":"2026041203505779000_2025.06.17.660083v1.46","first-page":"109","article-title":"A Chick Embryo in-Vitro Model of Knee Morphogenesis","volume":"4","year":"2016","journal-title":"Arch Bone Jt Surg"},{"key":"2026041203505779000_2025.06.17.660083v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.01.010"},{"key":"2026041203505779000_2025.06.17.660083v1.48","doi-asserted-by":"publisher","DOI":"10.22203\/ecm.v026a07"},{"key":"2026041203505779000_2025.06.17.660083v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2016.09.029"},{"key":"2026041203505779000_2025.06.17.660083v1.50","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v041a34"},{"key":"2026041203505779000_2025.06.17.660083v1.51","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade2155"},{"key":"2026041203505779000_2025.06.17.660083v1.52","doi-asserted-by":"crossref","unstructured":"Parisi, C. , Chandaria, V. V. & Nowlan, N. C . Blocking mechanosensitive ion channels eliminates the effects of applied mechanical loading on chick joint morphogenesis. Philosophical Transactions of the Royal Society B: Biological Sciences 373, 20170317 (2018).","DOI":"10.1098\/rstb.2017.0317"},{"key":"2026041203505779000_2025.06.17.660083v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2023.11.029"},{"key":"2026041203505779000_2025.06.17.660083v1.54","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.231023"},{"key":"2026041203505779000_2025.06.17.660083v1.55","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v044a08"},{"key":"2026041203505779000_2025.06.17.660083v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.11.026"},{"key":"2026041203505779000_2025.06.17.660083v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.04.013"},{"key":"2026041203505779000_2025.06.17.660083v1.58","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-011-0304-4"},{"key":"2026041203505779000_2025.06.17.660083v1.59","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000000547"},{"key":"2026041203505779000_2025.06.17.660083v1.60","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13151"},{"key":"2026041203505779000_2025.06.17.660083v1.61","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13087"},{"key":"2026041203505779000_2025.06.17.660083v1.62","doi-asserted-by":"publisher","DOI":"10.1097\/aog.0000000000003772"},{"key":"2026041203505779000_2025.06.17.660083v1.63","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009223"},{"key":"2026041203505779000_2025.06.17.660083v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2017.01.023"},{"key":"2026041203505779000_2025.06.17.660083v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajogmf.2020.100095"},{"key":"2026041203505779000_2025.06.17.660083v1.66","doi-asserted-by":"publisher","DOI":"10.1080\/13803395.2016.1227427"},{"key":"2026041203505779000_2025.06.17.660083v1.67","doi-asserted-by":"publisher","DOI":"10.1113\/JP275758"},{"key":"2026041203505779000_2025.06.17.660083v1.68","doi-asserted-by":"crossref","unstructured":"Son, J. S. et al. Maternal Inactivity Programs Skeletal Muscle Dysfunction in Offspring Mice by Attenuating Apelin Signaling and Mitochondrial Biogenesis. Cell Rep 33, (2020).","DOI":"10.1016\/j.celrep.2020.108461"},{"key":"2026041203505779000_2025.06.17.660083v1.69","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-83329-z"},{"key":"2026041203505779000_2025.06.17.660083v1.70","first-page":"2868","article-title":"Quantification of placental change in mouse models of preeclampsia using magnetic resonance microscopy","volume":"62","year":"2018","journal-title":"Eur J Histochem"},{"key":"2026041203505779000_2025.06.17.660083v1.71","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902688116"},{"key":"2026041203505779000_2025.06.17.660083v1.72","doi-asserted-by":"publisher","DOI":"10.3390\/ijms150916153"},{"key":"2026041203505779000_2025.06.17.660083v1.73","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00888"},{"key":"2026041203505779000_2025.06.17.660083v1.74","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-020-00605-3"},{"key":"2026041203505779000_2025.06.17.660083v1.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajogmf.2020.100095"},{"key":"2026041203505779000_2025.06.17.660083v1.76","doi-asserted-by":"publisher","DOI":"10.1080\/13803395.2016.1227427"},{"key":"2026041203505779000_2025.06.17.660083v1.77","doi-asserted-by":"publisher","DOI":"10.12965\/jer.2040822.411"},{"key":"2026041203505779000_2025.06.17.660083v1.78","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154704"},{"key":"2026041203505779000_2025.06.17.660083v1.79","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72022-6"},{"key":"2026041203505779000_2025.06.17.660083v1.80","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1097\/CEJ.0000000000000029","article-title":"Maternal exercise during pregnancy reduces risk of mammary tumorigenesis in rat offspring","volume":"23","year":"2014","journal-title":"European Journal of Cancer Prevention"},{"key":"2026041203505779000_2025.06.17.660083v1.81","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1583530"},{"key":"2026041203505779000_2025.06.17.660083v1.82","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2016.1140140"},{"key":"2026041203505779000_2025.06.17.660083v1.83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082378"},{"key":"2026041203505779000_2025.06.17.660083v1.84","first-page":"233","article-title":"Effects of physical exercise during pregnancy and protein malnutrition during pregnancy and lactation on the development and growth of the offspring\u2019s femur","volume":"86","year":"2010","journal-title":"J Pediatr (Rio J)"},{"key":"2026041203505779000_2025.06.17.660083v1.85","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-019-2441-1"},{"key":"2026041203505779000_2025.06.17.660083v1.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.109162"},{"key":"2026041203505779000_2025.06.17.660083v1.87","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00250.2020"},{"key":"2026041203505779000_2025.06.17.660083v1.88","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00082.2015"},{"key":"2026041203505779000_2025.06.17.660083v1.89","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-5576(02)00159-4"},{"key":"2026041203505779000_2025.06.17.660083v1.90","doi-asserted-by":"publisher","DOI":"10.1210\/en.133.3.1361"},{"key":"2026041203505779000_2025.06.17.660083v1.91","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2000.5926"},{"key":"2026041203505779000_2025.06.17.660083v1.92","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.073569"},{"key":"2026041203505779000_2025.06.17.660083v1.93","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1460023"},{"key":"2026041203505779000_2025.06.17.660083v1.94","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.3.1250"},{"key":"2026041203505779000_2025.06.17.660083v1.95","doi-asserted-by":"publisher","DOI":"10.1136\/fn.73.2.F87"},{"key":"2026041203505779000_2025.06.17.660083v1.96","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1994.tb02030.x"},{"key":"2026041203505779000_2025.06.17.660083v1.97","doi-asserted-by":"crossref","unstructured":"Hubrecht, R. C. & Carter, E . The 3rs and humane experimental technique: implementing change. Animals (Basel) 9, (2019).","DOI":"10.3390\/ani9100754"},{"key":"2026041203505779000_2025.06.17.660083v1.98","first-page":"120","article-title":"Russell and Burch\u2019s 3Rs then and now: the need for clarity in definition and purpose","volume":"54","year":"2015","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"2026041203505779000_2025.06.17.660083v1.99","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23485"},{"key":"2026041203505779000_2025.06.17.660083v1.100","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420220306"},{"key":"2026041203505779000_2025.06.17.660083v1.101","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot5639"},{"key":"2026041203505779000_2025.06.17.660083v1.102","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068206"},{"key":"2026041203505779000_2025.06.17.660083v1.103","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2007.09.031"},{"key":"2026041203505779000_2025.06.17.660083v1.104","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2012.05.001"},{"key":"2026041203505779000_2025.06.17.660083v1.105","first-page":"1","article-title":"Multiplexed tape-stabilized cryohistology of mineralized large animal specimens","volume":"9","author":"X","year":"2022","journal-title":"J Biol Methods"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.17.660083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:02:31Z","timestamp":1782277351000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.06.17.660083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,17]]},"references-count":105,"URL":"https:\/\/doi.org\/10.1101\/2025.06.17.660083","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1096\/fj.202503192R","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,6,17]]},"subtype":"preprint"}}