{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:58:06Z","timestamp":1786460286862,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371635"],"award-info":[{"award-number":["82371635"]}],"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":["82401890"],"award-info":[{"award-number":["82401890"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009558","name":"University Natural Science Research Project of Anhui Province","doi-asserted-by":"publisher","award":["2023AH053308"],"award-info":[{"award-number":["2023AH053308"]}],"id":[{"id":"10.13039\/501100009558","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although previous studies have indicated that sleep deprivation may affect ejaculatory regulation, the underlying mechanisms are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to determine whether sleep deprivation disrupts tryptophan (Trp) metabolism and impairs ejaculatory control through modulation of tryptophan hydroxylase\u20102 (TPH2) and indoleamine\u20102,3\u2010dioxygenase\u20101 (IDO1) expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Male rats with normal ejaculatory function were randomly allocated to four groups: chronic sleep deprivation (CSD), CSD combined with subcutaneous injection of the IDO1 inhibitor 1\u2010methyl\u2010D, L\u2010tryptophan (1\u2010MT), CSD combined with physiological saline, and control. The expression levels of IDO1 and TPH2 in brain tissue were detected using Western blotting and immunohistochemistry. Enzyme\u2010linked immunosorbent assay was used to measure concentrations of interleukin\u20106 (IL\u20106), tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), Trp, kynurenine (Kyn), and serotonin (5\u2010hydroxytryptamine, 5\u2010HT) in brain tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Rats exposed to CSD or CSD plus saline exhibited significantly shorter ejaculation latency (EL) than controls; however, 1\u2010MT administration increased latency. The CSD and CSD + saline groups had the lowest TPH2 expression and the highest IDO1 expression in the brain. Although the expression levels of IDO1 in the CSD + 1\u2010MT group did not significantly decrease, TPH2 levels were partially restored. According to correlation analysis, EL was adversely connected with Kyn pathway activity, which was shown by an increased Kyn\/Trp ratio.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings indicate that sleep deprivation accelerates ejaculation, possibly through activation of the Kyn metabolic pathway. Increased IDO1 and reduced TPH2 expression in the brain may hyperactivate the Kyn pathway, thereby accelerating ejaculation. Inhibition of IDO1 partially reversed this alteration and prolonged ejaculatory latency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This work provides new insights into the pathophysiological mechanism of acquired premature ejaculation (APE) caused by sleep deprivation and suggests prospective treatment strategies by identifying a critical role for brain IDO1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70341","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:41:21Z","timestamp":1786452081000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Sleep Deprivation Accelerates Ejaculation by Shifting Brain Tryptophan Metabolism Toward the Kynurenine Pathway in Male Rats"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0426-4643","authenticated-orcid":false,"given":"Zhi","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-0175","authenticated-orcid":false,"given":"Tianle","family":"Zhu","sequence":"additional","affiliation":[{"name":"Urology &amp; Nephrology Center Department of Urology Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9391-1780","authenticated-orcid":false,"given":"Yunlong","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8091-6809","authenticated-orcid":false,"given":"Yao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4233-1118","authenticated-orcid":false,"given":"Yuanyuan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8479-6779","authenticated-orcid":false,"given":"Yukuai","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6003-5182","authenticated-orcid":false,"given":"Xiansheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"11","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/s41585-022-00639-5","article-title":"Current and Emerging Treatment Options for Premature Ejaculation","volume":"19","author":"Gul M.","year":"2022","journal-title":"Nature Reviews Urology"},{"issue":"3","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.eururo.2021.06.007","article-title":"European Association of Urology Guidelines on Sexual and Reproductive Health\u20102021 Update: Male Sexual Dysfunction","volume":"80","author":"Salonia A.","year":"2021","journal-title":"European Urology"},{"issue":"2","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/medu.14296","article-title":"Acute and Chronic Sleep Deprivation in Residents: Cognition and Stress Biomarkers","volume":"55","author":"Choshen\u2010Hillel S.","year":"2021","journal-title":"Medical Education"},{"issue":"3","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.juro.2007.10.024","article-title":"Erectile Dysfunction and Sleep Related Disorders","volume":"179","author":"Jankowski J. 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