{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T11:25:13Z","timestamp":1763810713521,"version":"3.40.5"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2021,10,25]]},"abstract":"<jats:p>Methotrexate (MTX) is a folic acid antagonist, widely used as a chemotherapeutic and immunosuppressive drug, but it is toxic to reproductive systems. In recent years, the era of stem cell applications becomes a promising point as a possible therapeutic agent in male infertility. This study is aimed at evaluating the therapeutic effects of stem cells at histological, molecular, biochemical, and functional levels in a methotrexate-induced testicular damage model. Material and Methods. Thirty rats were divided randomly into three groups (ten rats each): group 1 (control): animals received an intraperitoneal injection of 2\u2009ml phosphate-buffered saline per week for 4 weeks, group 2 (MTX-treated group): animals were intraperitoneally injected with methotrexate (8\u2009mg\/kg) once weekly for 4 weeks, and group 3 (ADMSC-treated group): methotrexate-treated animals received a single dose of<jats:inline-formula><a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><a:mn>1<\/a:mn><a:mo>\u00d7<\/a:mo><a:msup><a:mrow><a:mn>10<\/a:mn><\/a:mrow><a:mrow><a:mn>6<\/a:mn><\/a:mrow><\/a:msup><\/a:math><\/jats:inline-formula>stem cells\/rat at the 5th week. At the 8th week, blood samples were collected for hormonal analysis; then, animals were sacrificed. The testes were dissected; the right testis was stained with hematoxylin and eosin. Random sections were taken from group 3 and examined with a fluorescent microscope. The left testis was divided into two specimens: the first was used for an electron microscope and the second was homogenized for molecular and biochemical assessments. Results. Group 2 showed significant histological changes, decreased free testosterone level, decrease in stem cell factor expression, and dysfunction of the oxidation state. The results revealed significant improvement of these parameters. Conclusion. Transplantation of adipose tissue-derived stem cells (ADMSCs) can improve the testicular damage histologically and functionally in a rat model.<\/jats:p>","DOI":"10.1155\/2021\/8450721","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:05:31Z","timestamp":1635206731000},"page":"1-13","source":"Crossref","is-referenced-by-count":6,"title":["Therapeutic Effect of Stem Cells on Male Infertility in a Rat Model: Histological, Molecular, Biochemical, and Functional Study"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-8944","authenticated-orcid":true,"given":"Sally S.","family":"Mohammed","sequence":"first","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Suez Canal University, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8021-5348","authenticated-orcid":true,"given":"Mona F.","family":"Mansour","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine, Suez Canal University, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2774-7599","authenticated-orcid":true,"given":"Noha A.","family":"Salem","sequence":"additional","affiliation":[{"name":"Anatomy and Embryology Department, Faculty of Medicine, Suez Canal University, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0394-3"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8947548"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.02.002"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22445"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/489659"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.11.078"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06881-z"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1242\/dev.107086"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.09.015"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000265074.83288.09"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0235"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0531.2008.01189.x"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.04.007"},{"key":"14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.semcdb.2016.04.009","article-title":"Spermatogenesis in humans and its affecting factors","volume":"59","author":"F. T. L. Neto","year":"2016","journal-title":"Seminars in Cell & Developmental Biology"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-017-0399-1"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.20959\/wjpr20177-8745"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1080\/01913123.2019.1572256"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1860842"},{"issue":"12","key":"19","first-page":"5511","article-title":"Protective effects of carvacrol against methotrexate-induced testicular toxicity in rats","volume":"7","author":"M. Daggulli","year":"2014","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.3906\/sag-1909-52"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1177\/0960327120940361"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.22074\/ijfs.2015.4614"},{"issue":"4","key":"23","first-page":"998","article-title":"Vitamin D: an effective way to combat methotrexate-induced testis injury","volume":"9","author":"A. Yalcin","year":"2020","journal-title":"Medicine"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.5152\/EurJTher.2018.790"},{"issue":"2","key":"25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.18311\/jnr\/2021\/26014","article-title":"Amelioration of methotrexate-induced testicular toxicity in rats by two varieties of coconut water: effect on sperm characters, oxidative stress and testosterone levels","volume":"21","author":"B. Ommurugan","year":"2021","journal-title":"Journal of Natural Remedies"},{"key":"26","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-3-319-53298-1_3","article-title":"Human spermatogenesis and its regulation","volume-title":"Male Hypogonadism","author":"H. Chen","year":"2017"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_201811_16293"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1111\/and.13145"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3206807"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152161"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0079-0"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1254\/jpssuppl.WCP2018.0_PO4-4-1"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510511103"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2012.167"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.22038\/IJBMS.2018.29040.7010"},{"key":"36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.5489\/cuaj.3160","article-title":"An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis","volume":"10","author":"E. Kemahli","year":"2016","journal-title":"Canadian Urological Association Journal"}],"container-title":["Stem Cells International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/sci\/2021\/8450721.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/sci\/2021\/8450721.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/sci\/2021\/8450721.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T20:43:39Z","timestamp":1673642619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/sci\/2021\/8450721\/"}},"subtitle":[],"editor":[{"given":"Shuiqiao","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,25]]},"references-count":36,"alternative-id":["8450721","8450721"],"URL":"https:\/\/doi.org\/10.1155\/2021\/8450721","relation":{},"ISSN":["1687-9678","1687-966X"],"issn-type":[{"type":"electronic","value":"1687-9678"},{"type":"print","value":"1687-966X"}],"subject":[],"published":{"date-parts":[[2021,10,25]]}}}