{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:48:58Z","timestamp":1790887738329,"version":"4.1.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016714","name":"University of Sharjah","doi-asserted-by":"crossref","award":["1901090169"],"award-info":[{"award-number":["1901090169"]}],"id":[{"id":"10.13039\/100016714","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016714","name":"University of Sharjah","doi-asserted-by":"crossref","award":["# 1901090168"],"award-info":[{"award-number":["# 1901090168"]}],"id":[{"id":"10.13039\/100016714","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mechanical unloading of the body in the hindlimb unloaded (HU) mice induces pathology in multiple organs, but the effects on testes are poorly characterized. We investigated the histology and Raman spectroscopy of the mouse testes following HU condition. We divided male, c57BL\/6j mice into ground-based controls or experimental groups for two and four weeks of HU. The testes tissues were dissected after euthanasia to investigate histological and Raman spectroscopic analysis. We found an HU-induced atrophy of testes irrespective of the time duration (p\u2009&lt;\u20090.05). Histological analysis revealed that the HU induced epithelial thinning, luminal widening, and spermatozoa decline in the seminiferous tubules of the mouse testes. In addition, we found a thickening of the epididymal epithelia and tunica albuginea. These changes were accompanied by a generalized depression in the Raman spectra, indicating an altered concentration and\/or orientation of several molecules. We also report reduced signal intensities of hydroxyproline and tryptophan, potentially contributing to testicular pathology during HU. Taken together, our findings indicate that the two or four weeks of HU induce disruption of testicular architecture and molecular phenotypes. Our results may have implications for understanding and\/or treating male infertility associated with prolonged bed rest and spaceflight.<\/jats:p>","DOI":"10.1038\/s41598-022-22385-9","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T10:03:09Z","timestamp":1666087389000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hindlimb unloading induces time-dependent disruption of testicular histology in mice"],"prefix":"10.1038","volume":"12","author":[{"given":"Asima","family":"Karim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwan","family":"Qaisar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Azeem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josemin","family":"Jose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopika","family":"Ramachandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab Mohamed","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel","family":"Elmoselhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdos","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael M.","family":"Abdel-Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7663-8532","authenticated-orcid":false,"given":"Anu V.","family":"Ranade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"22385_CR1","doi-asserted-by":"crossref","unstructured":"Qaisar, R., Karim, A., & Elmoselhi, A.B.J.A.P. Muscle unloading: A comparison between spaceflight and ground\u2010based models. 228(3), e13431 (2020).","DOI":"10.1111\/apha.13431"},{"issue":"1","key":"22385_CR2","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12958-021-00694-4","volume":"19","author":"A Moustafa","year":"2021","unstructured":"Moustafa, A. Hindlimb unloading-induced reproductive suppression via Downregulation of hypothalamic Kiss-1 expression in adult male rats. Reprod. Biol. Endocrinol. 19(1), 37 (2021).","journal-title":"Reprod. Biol. Endocrinol."},{"key":"22385_CR3","first-page":"9","volume":"17","author":"Q Chen","year":"2006","unstructured":"Chen, Q., Zhu, W. & Li, J. Effects of aging on spermatogenesis, sperm maturation and fertility in mice. J. Reprod. Contracept. 17, 9\u201314 (2006).","journal-title":"J. Reprod. Contracept."},{"issue":"1","key":"22385_CR4","first-page":"101","volume":"5","author":"IA Nichiporuk","year":"1998","unstructured":"Nichiporuk, I. A. et al. Male reproductive system in conditions of bed-rest in a head-down tilt. 5(1), 101 (1998).","journal-title":"Male reproductive system in conditions of bed-rest in a head-down tilt."},{"issue":"10","key":"22385_CR5","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1152\/japplphysiol.00997.2015","volume":"120","author":"RK Globus","year":"2016","unstructured":"Globus, R. K. & Morey-Holton, E. Hindlimb unloading: rodent analog for microgravity. J. Appl. Physiol. 120(10), 1196\u20131206 (2016).","journal-title":"J. Appl. Physiol."},{"issue":"1","key":"22385_CR6","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41526-022-00211-w","volume":"8","author":"AA Khan","year":"2022","unstructured":"Khan, A. A. et al. Mitigating sarcoplasmic reticulum stress limits disuse-induced muscle loss in hindlimb unloaded mice. NPJ Microgravity 8(1), 24 (2022).","journal-title":"NPJ Microgravity"},{"issue":"10","key":"22385_CR7","first-page":"1","volume":"11","author":"R Siddiqui","year":"2021","unstructured":"Siddiqui, R. et al. Effect of Microgravity Environment on Gut Microbiome and Angiogenesis. Life (Basel) 11(10), 1 (2021).","journal-title":"Life (Basel)"},{"issue":"1","key":"22385_CR8","doi-asserted-by":"publisher","DOI":"10.1002\/phy2.12","volume":"1","author":"P Chowdhury","year":"2013","unstructured":"Chowdhury, P. et al. Animal model of simulated microgravity: A comparative study of hindlimb unloading via tail versus pelvic suspension. Physiol. Rep. 1(1), e00012 (2013).","journal-title":"Physiol. Rep."},{"key":"22385_CR9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actaastro.2022.02.025","volume":"195","author":"BB Anna Hawliczek","year":"2022","unstructured":"Anna Hawliczek, B. B. et al. Hind-limb unloading in rodents: Current evidence and perspectives. Acta Astronaut. 195, 1 (2022).","journal-title":"Acta Astronaut."},{"issue":"12","key":"22385_CR10","first-page":"12208","volume":"9","author":"C Wang","year":"2016","unstructured":"Wang, C. et al. Simulated weightlessness by tail-suspension affects follicle development and reproductive capacity in rats. 9(12), 12208\u201312218 (2016).","journal-title":"Simulated weightlessness by tail-suspension affects follicle development and reproductive capacity in rats."},{"issue":"12","key":"22385_CR11","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1590\/S0100-879X2011007500147","volume":"44","author":"Y Ding","year":"2011","unstructured":"Ding, Y. et al. The effect of microgravity on tissue structure and function of rat testis. Braz. J. Med. Biol. Res. 44(12), 1243\u20131250 (2011).","journal-title":"Braz. J. Med. Biol. Res."},{"issue":"3","key":"22385_CR12","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/j.1939-4640.1992.tb00305.x","volume":"13","author":"D Deaver","year":"1992","unstructured":"Deaver, D. et al. Effects of caudal elevation on testicular function in rats separation of effects on spermatogenesis and steroidogenesis. J. Androl. 13(3), 224\u2013231 (1992).","journal-title":"J. Androl."},{"issue":"2","key":"22385_CR13","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/aja.2012.167","volume":"15","author":"RJ Aitken","year":"2013","unstructured":"Aitken, R. J. Falling sperm counts twenty years on: where are we now?. Asian J. Androl. 15(2), 204 (2013).","journal-title":"Asian J. Androl."},{"issue":"3","key":"22385_CR14","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1177\/0960327117703690","volume":"37","author":"P Sengupta","year":"2018","unstructured":"Sengupta, P. et al. Decline in sperm count in European men during the past 50 years. Hum. Exp. Toxicol. 37(3), 247\u2013255 (2018).","journal-title":"Hum. Exp. Toxicol."},{"issue":"Suppl 1","key":"22385_CR15","first-page":"37","volume":"12","author":"PD Jost","year":"2008","unstructured":"Jost, P. D. Simulating human space physiology with bed rest. Hippokratia 12(Suppl 1), 37\u201340 (2008).","journal-title":"Hippokratia"},{"issue":"3","key":"22385_CR16","first-page":"254","volume":"20","author":"C Winkelman","year":"2009","unstructured":"Winkelman, C. Bed rest in health and critical illness: A body systems approach. AACN Adv. Crit. Care 20(3), 254\u2013266 (2009).","journal-title":"AACN Adv. Crit. Care"},{"issue":"4","key":"22385_CR17","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1111\/apha.12320","volume":"212","author":"M Maffei","year":"2014","unstructured":"Maffei, M. et al. Actin sliding velocity on pure myosin isoforms from hindlimb unloaded mice. Acta Physiol. (Oxf) 212(4), 316\u2013329 (2014).","journal-title":"Acta Physiol. (Oxf)"},{"key":"22385_CR18","volume":"25","author":"M Azeem","year":"2021","unstructured":"Azeem, M. et al. Signature molecular changes in the skeletal muscle of hindlimb unloaded mice. Biochem. Biophys. Rep. 25, 100930 (2021).","journal-title":"Biochem. Biophys. Rep."},{"key":"22385_CR19","doi-asserted-by":"crossref","unstructured":"Bancroft, J.D., & Layton, C. Connective and mesenchymal tissues with their stains. Bancroft\u2019s Theory and Practice of Histological Techniques, pp. 187\u2013214 (2012).","DOI":"10.1016\/B978-0-7020-4226-3.00011-1"},{"issue":"10","key":"22385_CR20","first-page":"742","volume":"52","author":"AV Ranade","year":"2011","unstructured":"Ranade, A. V. et al. Effect of vitamin E administration on histopathological changes in rat testes following torsion and detorsion. Singapore Med. J. 52(10), 742\u2013746 (2011).","journal-title":"Singapore Med. J."},{"issue":"3","key":"22385_CR21","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1095\/biolreprod43.3.525","volume":"43","author":"RA Hess","year":"1990","unstructured":"Hess, R. A. Quantitative and qualitative characteristics of the stages and transitions in the cycle of the rat seminiferous epithelium: Light microscopic observations of perfusion-fixed and plastic-embedded testes. Biol. Reprod. 43(3), 525\u2013542 (1990).","journal-title":"Biol. Reprod."},{"issue":"9","key":"22385_CR22","first-page":"1919","volume":"35","author":"D Liu","year":"2020","unstructured":"Liu, D. et al. Determination of cadmium induced acute and chronic reproductive toxicity with Raman spectroscopy. 35(9), 1919\u20131926 (2020).","journal-title":"Determination of cadmium induced acute and chronic reproductive toxicity with Raman spectroscopy."},{"key":"22385_CR23","doi-asserted-by":"crossref","unstructured":"Kim, S., et al., PubChem 2019 update: Improved access to chemical data. 47(D1), D1102\u2013D1109 (2019).","DOI":"10.1093\/nar\/gky1033"},{"issue":"1","key":"22385_CR24","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1210\/jc.2011-2233","volume":"97","author":"SM Smith","year":"2012","unstructured":"Smith, S. M. et al. Long-duration space flight and bed rest effects on testosterone and other steroids. J. Clin. Endocrinol. Metab. 97(1), 270\u2013278 (2012).","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"4","key":"22385_CR25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210770","volume":"14","author":"AM Foucaut","year":"2019","unstructured":"Foucaut, A. M. et al. Sedentary behavior, physical inactivity and body composition in relation to idiopathic infertility among men and women. PLoS ONE 14(4), e0210770 (2019).","journal-title":"PLoS ONE"},{"issue":"1","key":"22385_CR26","first-page":"1","volume":"13","author":"F Mehraein","year":"2011","unstructured":"Mehraein, F. & Negahdar, F. Morphometric evaluation of seminiferous tubules in aged mice testes after melatonin administration. Cell J. 13(1), 1\u20134 (2011).","journal-title":"Cell J."},{"key":"22385_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2020.570058","volume":"14","author":"F Jimenez-Trejo","year":"2020","unstructured":"Jimenez-Trejo, F. et al. Indolaminergic system in adult rat testes: Evidence for a local serotonin system. Front. Neuroanat. 14, 570058 (2020).","journal-title":"Front. Neuroanat."},{"issue":"36","key":"22385_CR28","doi-asserted-by":"publisher","first-page":"7754","DOI":"10.1021\/acs.jpcb.9b05006","volume":"123","author":"S Xu","year":"2019","unstructured":"Xu, S. et al. Unraveling the role of hydroxyproline in maintaining the thermal stability of the collagen triple helix structure using simulation. J. Phys. Chem. B 123(36), 7754\u20137763 (2019).","journal-title":"J. Phys. Chem. B"},{"issue":"10","key":"22385_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/md19100566","volume":"19","author":"X Zhang","year":"2021","unstructured":"Zhang, X. et al. The potential protective effect and possible mechanism of peptides from oyster (Crassostrea hongkongensis) hydrolysate on triptolide-induced testis injury in male mice. Mar. Drugs 19(10), 1 (2021).","journal-title":"Mar. Drugs"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-22385-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-22385-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-22385-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T01:51:37Z","timestamp":1701222697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-22385-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,18]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["22385"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-22385-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,18]]},"assertion":[{"value":"13 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17406"}}