{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T19:47:13Z","timestamp":1776714433114,"version":"3.51.2"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271686"],"award-info":[{"award-number":["82271686"]}],"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":["32000599"],"award-info":[{"award-number":["32000599"]}],"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":["U22A20277"],"award-info":[{"award-number":["U22A20277"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hainan Provincial Natural Science Foundation of China","award":["821RC686"],"award-info":[{"award-number":["821RC686"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M712438"],"award-info":[{"award-number":["2022M712438"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wuxi \u201cTwo Hundred Talents\u201d Project","award":["BJ2023074"],"award-info":[{"award-number":["BJ2023074"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,5]]},"abstract":"<jats:title>In brief<\/jats:title>\n                  <jats:p>Local testosterone regulation is critical for male fertility but poorly understood. We show that loss of CCDC117 triggers testosterone elevation despite lower luteinizing hormone levels, revealing a gonadotropin-independent compensatory mechanism that preserves fertility in smaller testes.<\/jats:p>\n                  <jats:p>AbstractThe local regulation of testicular steroidogenesis is essential for male fertility but remains incompletely understood. Here, we identify the testis-enriched protein CCDC117 as a critical, local brake on testicular testosterone production. Ccdc117 knockout mice exhibited a paradoxical phenotype: significant reduced testis size (\u223c21% reduction in weight) accompanied by diminished seminiferous tubule area, yet displaying fully preserved sperm production and near-normal fertility. Mechanistically, loss of CCDC117 triggers a cell-autonomous, compensatory upregulation of the steroidogenic pathway specifically in Leydig cells, leading to a 2-fold increase in serum testosterone without a rise in luteinizing hormone. Consistently, intratesticular testosterone levels were significantly elevated (\u223c1.5-fold), directly confirming enhanced local androgen production. This gonadotropin-independent hyperandrogenemia likely supports the maintenance of normal spermatogenic cell numbers within the compromised tubules, facilitating higher-efficiency spermatogenesis that ultimately preserves male fertility in the context of a smaller testis. Collectively, these findings demonstrate that CCDC117 deficiency releases a constitutive brake on Leydig cell steroidogenesis. The resulting compensatory hyperandrogenemia maintains reproductive function under structural compromise, thus uncovering a previously unrecognized local mechanism that ensures reproductive resilience.<\/jats:p>","DOI":"10.1093\/reprod\/xaag037","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:59:04Z","timestamp":1773838744000},"source":"Crossref","is-referenced-by-count":0,"title":["Ccdc117 deficiency triggers hyperandrogenemia, maintaining normal sperm production despite reduced testis size"],"prefix":"10.1093","volume":"171","author":[{"given":"Min","family":"Zang","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, Jiangsu, 210002,","place":["China"]},{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, School of Public Health, Nanjing Medical University , Nanjing 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Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linzi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, School of Public Health, Nanjing Medical University , Nanjing 211166,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9290-184X","authenticated-orcid":false,"given":"Yong","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiantian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3420-2220","authenticated-orcid":false,"given":"Bing","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, Jiangsu, 210002,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200011,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Center of Reproductive Medicine, Wuxi Maternity and Child Health Care Hospital, Nanjing Medical University , Wuxi, Jiangsu, 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