{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T18:56:31Z","timestamp":1768503391842,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,25]]},"group-title":"Bioengineering","reference-count":50,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Female adolescent athletes are at a higher risk of tearing their anterior cruciate ligament (ACL) than male counterparts. While most work related to hormones has focused on the effects of estrogen to understand the increased risk of ACL injury, there are other understudied factors, including testosterone. The purpose of this study was to determine how surgical castration in the male porcine model influences ACL size and function across skeletal growth. Thirty-six male Yorkshire crossbreed pigs were raised to 3 (juvenile), 4.5 (early adolescent), and 6 months (adolescent) of age. Animals were either castrated (barrows) within 1-2 weeks after birth or were left intact (boars). Post-euthanasia, joint and ACL size were assessed via MRI, and biomechanics were assessed via a robotic testing system. Joint size increased throughout age, yet barrows had smaller joints than boars (p&lt;0.001 for all measures). ACL cross-sectional area (CSA), length, volume, and stiffness increased with age (p&lt;0.0001), as did ACL anteromedial (AM) bundle percent contribution to resisting loads (p=0.012). Boar ACL, AM bundle, and PL bundle volumes were 19% (p=0.002), 25% (p=0.003), and 15% (p=0.04) larger than barrows across ages. However, CSA, stiffness, and bundle contribution were similar between boars and barrows (p&gt;0.05). The barrows had smaller temporal increases in AM bundle percent function than boars, but these data were highly variable. Thus, early and sustained loss in testosterone leads to subtle differences in ACL morphology, but may not influence measures associated with increased injury risk, such as CSA or bundle forces in response to applied loads.<\/jats:p>","DOI":"10.1101\/2023.01.24.524954","type":"posted-content","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T13:45:30Z","timestamp":1674654330000},"source":"Crossref","is-referenced-by-count":0,"title":["Neo-natal castration leads to subtle differences in porcine anterior cruciate ligament morphology and function in adolescence"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6868-407X","authenticated-orcid":false,"given":"Jacob D.","family":"Thompson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1596-9060","authenticated-orcid":false,"given":"Danielle","family":"Howe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9745-7722","authenticated-orcid":false,"given":"Emily H.","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-0870","authenticated-orcid":false,"given":"Matthew B.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023021812400587000_2023.01.24.524954v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocl.2014.11.004"},{"key":"2023021812400587000_2023.01.24.524954v2.2","doi-asserted-by":"crossref","unstructured":"Beck NA , Lawrence JTR , Nordin JD , et al. 2017. ACL tears in school-aged children and adolescents over 20 years. Pediatrics 139(3).","DOI":"10.1542\/peds.2016-1877"},{"issue":"2","key":"2023021812400587000_2023.01.24.524954v2.3","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00167-019-05553-9","article-title":"The incidence of paediatric ACL injury is increasing in Finland","volume":"28","year":"2020","journal-title":"Knee Surgery, Sport. Traumatol. Arthrosc"},{"key":"2023021812400587000_2023.01.24.524954v2.4","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0000000000000482"},{"issue":"7","key":"2023021812400587000_2023.01.24.524954v2.5","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1177\/0363546520959619","article-title":"Anterior Cruciate Ligament Injury Incidence in Adolescent Athletes: A Systematic Review and Meta-analysis","volume":"49","year":"2021","journal-title":"Am. J. Sports Med"},{"key":"2023021812400587000_2023.01.24.524954v2.6","doi-asserted-by":"publisher","DOI":"10.4085\/1062-6050-48.6.03."},{"issue":"3","key":"2023021812400587000_2023.01.24.524954v2.7","first-page":"294","article-title":"The incidence of injury in Texas high school basketball","volume":"27","year":"1999","journal-title":"A prospective study among male and female athletes. Am. J. Sports Med"},{"key":"2023021812400587000_2023.01.24.524954v2.8","doi-asserted-by":"publisher","DOI":"10.1177\/0363546516630927"},{"issue":"5","key":"2023021812400587000_2023.01.24.524954v2.9","doi-asserted-by":"crossref","first-page":"2325967120919178","DOI":"10.1177\/2325967120919178","article-title":"Sex-Based Differences in Anterior Cruciate Ligament Injuries Among United States High School Soccer Players: An Epidemiological Study","volume":"8","year":"2020","journal-title":"Orthop. J. Sport. Med"},{"issue":"4","key":"2023021812400587000_2023.01.24.524954v2.10","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1111\/sms.13041","article-title":"Basal and stress-induced salivary testosterone variation across the menstrual cycle and linkage to motivation and muscle power","volume":"28","year":"2018","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"2023021812400587000_2023.01.24.524954v2.11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.yhbeh.2019.04.007","article-title":"Within- and between-person variation in morning testosterone is associated with economic risk-related decisions in athletic women across the menstrual cycle","volume":"112","year":"2019","journal-title":"Horm. Behav"},{"key":"2023021812400587000_2023.01.24.524954v2.12","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2020-103173"},{"key":"2023021812400587000_2023.01.24.524954v2.13","doi-asserted-by":"crossref","first-page":"827726","DOI":"10.3389\/fphys.2022.827726","article-title":"Insights in the Effect of Fluctuating Female Hormones on Injury Risk\u2014Challenge and Chance","volume":"13","year":"2022","journal-title":"Front. Physiol"},{"issue":"5","key":"2023021812400587000_2023.01.24.524954v2.14","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1177\/03635465980260050301","article-title":"Association between the menstrual cycle and anterior cruciate ligament injuries in female athletes","volume":"26","year":"1998","journal-title":"Am. J. Sports Med"},{"issue":"3","key":"2023021812400587000_2023.01.24.524954v2.15","first-page":"275","article-title":"The menstrual cycle, sex hormones, and anterior cruciate ligament injury","volume":"37","year":"2002","journal-title":"J. Athl. Train"},{"issue":"2","key":"2023021812400587000_2023.01.24.524954v2.16","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1177\/03635465020300020601","article-title":"The effect of the menstrual cycle on anterior cruciate ligament injuries in women as determined by hormone levels","volume":"30","year":"2002","journal-title":"Am. J. Sports Med"},{"key":"2023021812400587000_2023.01.24.524954v2.17","doi-asserted-by":"publisher","DOI":"10.1249\/01.MSS.0000132270.43579.1A"},{"key":"2023021812400587000_2023.01.24.524954v2.18","doi-asserted-by":"publisher","DOI":"10.1007\/s00402-007-0461-1"},{"key":"2023021812400587000_2023.01.24.524954v2.19","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100150505"},{"issue":"9","key":"2023021812400587000_2023.01.24.524954v2.20","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1007\/s00167-014-3077-3","article-title":"The influence of sex hormones on anterior cruciate ligament rupture: female study","volume":"23","year":"2015","journal-title":"Knee Surgery, Sport. Traumatol. Arthrosc"},{"key":"2023021812400587000_2023.01.24.524954v2.21","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3389\/fgene.2019.00505","article-title":"Testosterone deficiency caused by castration modulates mitochondrial biogenesis through the AR\/PGC1\u03b1\/TFAM pathway","volume":"10","year":"2019","journal-title":"Front. Genet"},{"issue":"6","key":"2023021812400587000_2023.01.24.524954v2.22","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.knee.2016.07.004","article-title":"Testosterone may increase rat anterior cruciate ligament strength","volume":"23","year":"2016","journal-title":"Knee"},{"issue":"12","key":"2023021812400587000_2023.01.24.524954v2.23","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1002\/jor.23594","article-title":"Orientation changes in the cruciate ligaments of the knee during skeletal growth: A porcine model","volume":"35","year":"2017","journal-title":"J. Orthop. Res"},{"issue":"9","key":"2023021812400587000_2023.01.24.524954v2.24","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1097\/CORR.0000000000000884.","article-title":"Biomechanical Function and Size of the Anteromedial and Posterolateral Bundles of the ACL Change Differently with Skeletal Growth in the Pig Model","volume":"477","year":"2019","journal-title":"Clin. Orthop. Relat. Res"},{"key":"2023021812400587000_2023.01.24.524954v2.25","doi-asserted-by":"crossref","unstructured":"Cone SG , Piedrahita JA , Spang JT , Fisher MB. 2019. In situ joint stiffness increases during skeletal growth but decreases following partial and complete anterior cruciate ligament injury. J. Biomech. Eng. 141(12).","DOI":"10.1115\/1.4044582"},{"key":"2023021812400587000_2023.01.24.524954v2.26","doi-asserted-by":"crossref","first-page":"109636","DOI":"10.1016\/j.jbiomech.2020.109636","article-title":"Joint laxity varies in response to partial and complete anterior cruciate ligament injuries throughout skeletal growth","volume":"101","year":"2020","journal-title":"J. Biomech"},{"key":"2023021812400587000_2023.01.24.524954v2.27","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.01368"},{"issue":"8","key":"2023021812400587000_2023.01.24.524954v2.28","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1002\/jor.21070","article-title":"Immature animals have higher cellular density in the healing anterior cruciate ligament than adolescent or adult animals","volume":"28","year":"2010","journal-title":"J. Orthop. Res"},{"key":"2023021812400587000_2023.01.24.524954v2.29","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25198"},{"issue":"8","key":"2023021812400587000_2023.01.24.524954v2.30","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1002\/jor.25207","article-title":"Sex-specific biomechanics and morphology of the anterior cruciate ligament during skeletal growth in a porcine model","volume":"40","year":"2022","journal-title":"J. Orthop. Res"},{"key":"2023021812400587000_2023.01.24.524954v2.31","doi-asserted-by":"crossref","unstructured":"Debski RE , Yamakawa S , Musahl V , Fujie H. 2017. Use of Robotic Manipulators to Study Diarthrodial Joint Function. J. Biomech. Eng. 139(2).","DOI":"10.1115\/1.4035644"},{"key":"2023021812400587000_2023.01.24.524954v2.32","doi-asserted-by":"publisher","DOI":"10.1115\/1.2792266"},{"key":"2023021812400587000_2023.01.24.524954v2.33","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jbiomech.2017.09.032","article-title":"New parameters describing how knee ligaments carry force in situ predict interspecimen variations in laxity during simulated clinical exams","volume":"64","year":"2017","journal-title":"J. Biomech"},{"key":"2023021812400587000_2023.01.24.524954v2.34","doi-asserted-by":"crossref","unstructured":"Satop\u00e4\u00e4 V , Albrecht J , Irwin D , Raghavan B. 2011. Finding a \u201ckneedle\u201d in a haystack: Detecting knee points in system behavior. Proc. - Int. Conf. Distrib. Comput. Syst. :166\u2013171.","DOI":"10.1109\/ICDCSW.2011.20"},{"issue":"3","key":"2023021812400587000_2023.01.24.524954v2.35","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0950-3293(03)00069-7","article-title":"Fresh and eating pork quality from entire versus castrate heavy males","volume":"15","year":"2004","journal-title":"Food Qual. Prefer"},{"issue":"4","key":"2023021812400587000_2023.01.24.524954v2.36","first-page":"797","article-title":"Developmental comparisons of boars and barrows: II","volume":"61","year":"1985","journal-title":"Body composition and bone development. J. Anim. Sci"},{"issue":"4","key":"2023021812400587000_2023.01.24.524954v2.37","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2527\/jas1985.614789x","article-title":"Developmental comparisons of boars and barrows: I. Growth rate, carcass and muscle characteristics","volume":"61","year":"1985","journal-title":"J. Anim. Sci"},{"issue":"1","key":"2023021812400587000_2023.01.24.524954v2.38","first-page":"185","article-title":"INFLUENCE OF DIET AND SEX-TYPE (BOAR, CASTRATE OR GILT) ON LIVE AND CARCASS MEASUREMENTS OF SELF-FED PIGS FROM TWO BREED LINES DIFFERING IN GROWTH RATES","volume":"65","year":"1985","journal-title":"undefined"},{"key":"2023021812400587000_2023.01.24.524954v2.39","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199607043350101"},{"key":"2023021812400587000_2023.01.24.524954v2.40","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0000000000000375"},{"issue":"4","key":"2023021812400587000_2023.01.24.524954v2.41","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1002\/jor.24748","article-title":"Age-related changes in ACL morphology during skeletal growth and maturation are different between females and males","volume":"39","year":"2021","journal-title":"J. Orthop. Res"},{"issue":"8","key":"2023021812400587000_2023.01.24.524954v2.42","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1097\/BPO.0000000000001611","article-title":"ACL Growth With Age in Pediatric Patients: An MRI Study","volume":"40","year":"2020","journal-title":"J. Pediatr. Orthop"},{"key":"2023021812400587000_2023.01.24.524954v2.43","doi-asserted-by":"publisher","DOI":"10.1177\/0363546505280426"},{"issue":"8","key":"2023021812400587000_2023.01.24.524954v2.44","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.2460\/ajvr.73.8.1186","article-title":"Sex hormone regulation of collagen concentrations in cranial cruciate ligaments of sexually immature male rabbits","volume":"73","year":"2012","journal-title":"Am. J. Vet. Res"},{"key":"2023021812400587000_2023.01.24.524954v2.45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.1978.tb00603.x"},{"key":"2023021812400587000_2023.01.24.524954v2.46","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12398"},{"issue":"8","key":"2023021812400587000_2023.01.24.524954v2.47","doi-asserted-by":"crossref","first-page":"703","DOI":"10.2106\/JBJS.19.00535","article-title":"Knee Morphological Risk Factors for Anterior Cruciate Ligament Injury: A Systematic Review","volume":"102","year":"2020","journal-title":"J. Bone Joint Surg. Am"},{"key":"2023021812400587000_2023.01.24.524954v2.48","doi-asserted-by":"publisher","DOI":"10.1007\/s00167-009-0813-1"},{"issue":"1","key":"2023021812400587000_2023.01.24.524954v2.49","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1152\/jappl.1989.66.1.498","article-title":"Effect of testosterone on muscle mass and muscle protein synthesis","volume":"66","year":"1989","journal-title":"J. Appl. Physiol"},{"issue":"7 suppl6","key":"2023021812400587000_2023.01.24.524954v2.50","first-page":"2325967117S0026","article-title":"Testosterone Supplementation Increases Lean Mass in Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial","volume":"5","year":"2017","journal-title":"Orthop. J. Sport. Med"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.01.24.524954","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:11:11Z","timestamp":1768450271000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.01.24.524954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":50,"URL":"https:\/\/doi.org\/10.1101\/2023.01.24.524954","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1115\/1.4063744","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,1,25]]},"subtype":"preprint"}}