{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:15Z","timestamp":1787028495277,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai science and technology innovation action plan project","award":["20Y11907600"],"award-info":[{"award-number":["20Y11907600"]}]},{"name":"Shanghai science and technology innovation action plan project","award":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"],"award-info":[{"award-number":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"]}]},{"name":"Shanghai science and technology innovation action plan project","award":["82001530, 81903417, 81871215, and 81971368"],"award-info":[{"award-number":["82001530, 81903417, 81871215, and 81971368"]}]},{"name":"Shanghai science and technology innovation action plan project","award":["2020BFH02002"],"award-info":[{"award-number":["2020BFH02002"]}]},{"name":"Shanghai science and technology innovation action plan project","award":["20YF1439500 and 20YF1453700"],"award-info":[{"award-number":["20YF1439500 and 20YF1453700"]}]},{"name":"Clinical Research Innovation Plan of Shanghai General Hospital","award":["20Y11907600"],"award-info":[{"award-number":["20Y11907600"]}]},{"name":"Clinical Research Innovation Plan of Shanghai General Hospital","award":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"],"award-info":[{"award-number":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"]}]},{"name":"Clinical Research Innovation Plan of Shanghai General Hospital","award":["82001530, 81903417, 81871215, and 81971368"],"award-info":[{"award-number":["82001530, 81903417, 81871215, and 81971368"]}]},{"name":"Clinical Research Innovation Plan of Shanghai General Hospital","award":["2020BFH02002"],"award-info":[{"award-number":["2020BFH02002"]}]},{"name":"Clinical Research Innovation Plan of Shanghai General Hospital","award":["20YF1439500 and 20YF1453700"],"award-info":[{"award-number":["20YF1439500 and 20YF1453700"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20Y11907600"],"award-info":[{"award-number":["20Y11907600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"],"award-info":[{"award-number":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001530, 81903417, 81871215, and 81971368"],"award-info":[{"award-number":["82001530, 81903417, 81871215, and 81971368"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020BFH02002"],"award-info":[{"award-number":["2020BFH02002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20YF1439500 and 20YF1453700"],"award-info":[{"award-number":["20YF1439500 and 20YF1453700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Key Project of Research and Development of Ningxia Hui Autonomous Region of China","award":["20Y11907600"],"award-info":[{"award-number":["20Y11907600"]}]},{"name":"the Key Project of Research and Development of Ningxia Hui Autonomous Region of China","award":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"],"award-info":[{"award-number":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"]}]},{"name":"the Key Project of Research and Development of Ningxia Hui Autonomous Region of China","award":["82001530, 81903417, 81871215, and 81971368"],"award-info":[{"award-number":["82001530, 81903417, 81871215, and 81971368"]}]},{"name":"the Key Project of Research and Development of Ningxia Hui Autonomous Region of China","award":["2020BFH02002"],"award-info":[{"award-number":["2020BFH02002"]}]},{"name":"the Key Project of Research and Development of Ningxia Hui Autonomous Region of China","award":["20YF1439500 and 20YF1453700"],"award-info":[{"award-number":["20YF1439500 and 20YF1453700"]}]},{"name":"Shanghai Sailing Program","award":["20Y11907600"],"award-info":[{"award-number":["20Y11907600"]}]},{"name":"Shanghai Sailing Program","award":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"],"award-info":[{"award-number":["CTCCR-2021C17, KD007-ly01, CTCCR-C04"]}]},{"name":"Shanghai Sailing Program","award":["82001530, 81903417, 81871215, and 81971368"],"award-info":[{"award-number":["82001530, 81903417, 81871215, and 81971368"]}]},{"name":"Shanghai Sailing Program","award":["2020BFH02002"],"award-info":[{"award-number":["2020BFH02002"]}]},{"name":"Shanghai Sailing Program","award":["20YF1439500 and 20YF1453700"],"award-info":[{"award-number":["20YF1439500 and 20YF1453700"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging has a significant negative impact on human testicular function; steroidogenesis is gradually impaired, and testosterone replacement therapy still has many risks. Low-intensity pulsed ultrasound (LIPUS) has been used as a novel non-invasive treatment for male erectile dysfunction and other fields, and has been shown to increase testosterone levels in animal models. Testosterone is synthesized and secreted by Leydig cells (LCs), and the serum testosterone level decreases after aging due to the LCs senescence. However, the effect of LIPUS on human senescent LCs has not been reported. In this study, human senescent LCs were isolated and stimulated with different energy intensities in vitro, and cell morphology, cell apoptosis, cell proliferation, cell senescence levels, lipid droplet number, testosterone and INSL3 secretion levels were tested and analyzed. Quantitative Polymerase Chain Reaction (QPCR) and Western Blot were performed to compare cell senescence characteristics and the expression profile of key pathways of testosterone secretion, and transcriptome analysis was performed to explore the signaling pathways of LCs alteration after LIPUS stimulation. It was safe and effective to stimulate LCs with the 75 mW\/cm2 energy of LIPUS in vitro, which not only improved the senescence phenotype, but also effectively enhanced the secretory function of LCs in vitro, and increased the expression of key pathways of the testosterone synthesis pathway. These results suggest that LIPUS could be used as a novel treatment to human senescent LCs with decreased testosterone secretion levels in vitro.<\/jats:p>","DOI":"10.3390\/ijms24010418","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:45:54Z","timestamp":1672116354000},"page":"418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Low-Intensity Pulsed Ultrasound Alleviates Human Testicular Leydig Cell Senescence In Vitro"],"prefix":"10.3390","volume":"24","author":[{"given":"Sha","family":"Han","sequence":"first","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-7759","authenticated-orcid":false,"given":"Shuai","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chencheng","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhui","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erlei","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujie","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Andrology, The Center for Men\u2019s Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1530\/EJE-12-0890","article-title":"Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: Longitudinal results from the European Male Ageing Study","volume":"168","author":"Camacho","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111179","DOI":"10.1016\/j.mce.2021.111179","article-title":"Differentiation of seminiferous tubule-associated stem cells into leydig cell and myoid cell lineages","volume":"525","author":"Zhao","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1054\/tice.1999.0092","article-title":"Peroxisomes and intracellular cholesterol trafficking in adult rat Leydig cells following Luteinizing hormone stimulation","volume":"32","year":"2000","journal-title":"Tissue Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.devcel.2022.04.004","article-title":"Single-cell analysis of human testis aging and correlation with elevated body mass index","volume":"57","author":"Nie","year":"2022","journal-title":"Dev. Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1093\/humrep\/deaa271","article-title":"Age-related changes in human Leydig cell status","volume":"35","author":"Mularoni","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"255","DOI":"10.21037\/tau.2016.02.04","article-title":"Clinical applications of low-intensity pulsed ultrasound and its potential role in urology","volume":"5","author":"Xin","year":"2016","journal-title":"Transl. Androl. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1093\/cvr\/cvaa221","article-title":"Low-intensity pulsed ultrasound ameliorates cardiac diastolic dysfunction in mice: A possible novel therapy for heart failure with preserved left ventricular ejection fraction","volume":"117","author":"Monma","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_8","first-page":"697","article-title":"Effect of low-intensity pulsed ultrasound on prepubertal rat testis","volume":"24","author":"Haddad","year":"1991","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_9","first-page":"13","article-title":"Stimulation of prepubertal, pubertal and adult rat testis with low-intensity pulsed ultrasound","volume":"102","author":"Haddad","year":"1994","journal-title":"Arch. Int. Physiol. Biochim. Biophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"599149","DOI":"10.3389\/fendo.2021.599149","article-title":"Androgen and Luteinizing Hormone Stimulate the Function of Rat Immature Leydig Cells Through Different Transcription Signals","volume":"12","author":"Li","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/biolre\/ioy059","article-title":"Leydig cells: Formation, function, and regulation","volume":"99","author":"Zirkin","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1073\/pnas.1519395113","article-title":"Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes","volume":"113","author":"Li","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1530\/REP-17-0346","article-title":"Isolation of human testicular cells and co-culture with embryonic stem cells","volume":"155","author":"Gaur","year":"2018","journal-title":"Reproduction"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22721","DOI":"10.3390\/ijms141122721","article-title":"Genes responsive to low-intensity pulsed ultrasound in MC3T3-E1 preosteoblast cells","volume":"14","author":"Tabuchi","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular Senescence: Defining a Path Forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"625434","DOI":"10.1155\/2012\/625434","article-title":"Hypogonadism in the aging male diagnosis, potential benefits, and risks of testosterone replacement therapy","volume":"2012","author":"Surampudi","year":"2012","journal-title":"Int. J. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"192","DOI":"10.4103\/1008-682X.122336","article-title":"Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment","volume":"16","author":"Huhtaniemi","year":"2014","journal-title":"Asian J. Androl."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1097\/JU.0000000000000579","article-title":"Testis Sparing Surgery of Small Testicular Masses: Retrospective Analysis of a Multicenter Cohort","volume":"203","author":"Gentile","year":"2020","journal-title":"J. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41569-019-0211-4","article-title":"Testosterone replacement therapy and cardiovascular risk","volume":"16","author":"Basaria","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1093\/aje\/kwz138","article-title":"Testosterone Replacement Therapy and the Risk of Prostate Cancer in Men with Late-Onset Hypogonadism","volume":"188","author":"Santella","year":"2019","journal-title":"Am. J. Epidemiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/bs.vh.2014.12.006","article-title":"Pharmacological regulation of the cholesterol transport machinery in steroidogenic cells of the testis","volume":"98","author":"Aghazadeh","year":"2015","journal-title":"Vitam. Horm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/j.1939-4640.2001.tb02165.x","article-title":"Leydig cell aging: Steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme","volume":"22","author":"Luo","year":"2001","journal-title":"J. Androl."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/j.1939-4640.2005.tb02868.x","article-title":"Temporal relationships among testosterone production, steroidogenic acute regulatory protein (StAR), and P450 side-chain cleavage enzyme (P450scc) during Leydig cell aging","volume":"26","author":"Luo","year":"2005","journal-title":"J. Androl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/humupd\/dmp011","article-title":"Biology of insulin-like factor 3 in human reproduction","volume":"15","author":"Ivell","year":"2009","journal-title":"Hum. Reprod. Update."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1111\/andr.13220","article-title":"Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort","volume":"10","author":"Heng","year":"2022","journal-title":"Andrology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/S1470-2045(10)70261-8","article-title":"Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: A phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity","volume":"11","author":"Wilson","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1101\/gad.331272.119","article-title":"Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence","volume":"34","author":"Vizioli","year":"2020","journal-title":"Genes Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/nm.4385","article-title":"Targeting cellular senescence prevents age-related bone loss in mice","volume":"23","author":"Farr","year":"2017","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/aja.2011.63","article-title":"Medical therapy for spermatogenic failure","volume":"14","author":"Ramasamy","year":"2012","journal-title":"Asian J. Androl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.1210\/en.2014-1688","article-title":"Testosterone treatment is a potent tumor promoter for the rat prostate","volume":"155","author":"Bosland","year":"2014","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Xu, L., Freeman, G., Cowling, B.J., and Schooling, C.M. (2013). Testosterone therapy and cardiovascular events among men: A systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-108"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"349","DOI":"10.23736\/S2724-6051.20.03646-2","article-title":"Incidence, predictive factors and survival outcomes of incidental prostate cancer in patients who underwent radical cystectomy for bladder cancer","volume":"73","author":"Claps","year":"2021","journal-title":"Minerva Urol. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.18632\/aging.102682","article-title":"FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice","volume":"12","author":"Zhang","year":"2020","journal-title":"Aging"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"306","DOI":"10.4252\/wjsc.v8.i10.306","article-title":"Stem cell therapy for the treatment of Leydig cell dysfunction in primary hypogonadism","volume":"8","author":"Peak","year":"2016","journal-title":"World J. Stem Cells"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41585-021-00480-2","article-title":"Advances in stem cell research for the treatment of primary hypogonadism","volume":"18","author":"Li","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_36","first-page":"1432","article-title":"Observation on the effectiveness and safety of different frequencies of low-intensity pulsed ultrasonic mechanical force in the treatment of erectile dysfunction","volume":"100","author":"Xia","year":"2020","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.eururo.2016.05.050","article-title":"Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis","volume":"71","author":"Lu","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.exger.2015.02.014","article-title":"Leydig cell aging and hypogonadism","volume":"68","author":"Beattie","year":"2015","journal-title":"Exp. Gerontol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mce.2008.07.016","article-title":"Leydig cell aging and the mechanisms of reduced testosterone synthesis","volume":"299","author":"Midzak","year":"2009","journal-title":"Mol. Cell. Endocrinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/418\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:52:10Z","timestamp":1760147530000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,27]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010418"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010418","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,27]]}}}