{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:54:54Z","timestamp":1773921294885,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Fujian Provincial Natural Science Foundation of China","award":["2024J08191"],"award-info":[{"award-number":["2024J08191"]}]},{"name":"Scientific Research Foundation of Jimei University","award":["ZQ2022019"],"award-info":[{"award-number":["ZQ2022019"]}]},{"name":"Scientific Research Foundation of Jimei University","award":["ZQ2020003"],"award-info":[{"award-number":["ZQ2020003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Testicular homeostasis relies on intricate germ cell\u2013somatic cell interactions, yet underlying regulatory mechanisms remain poorly understood. While cilia-related nphp4 mutations cause male infertility, phenotypes show notable interspecies differences and the driving mechanism remains unknown. In this study, we used the Japanese medaka (Oryzias latipes), a model with unique cystic spermatogenesis, to investigate the role of nphp4 in male reproduction. In situ hybridization localized nphp4 transcripts within the spermatogonial niche, particularly in gsdf-positive Sertoli cells. CRISPR\/Cas9-mediated deficiency of nphp4 led to age-dependent infertility, characterized by a significant decline in fertilization rates. Although sperm retained normal flagellar structure, they exhibited severe motility defects, head abnormalities, and mitochondrial damage by 6\u2009months of age. Notably, somatic cell dysfunction, including Sertoli cell apoptosis and altered expression of functional markers, occurred early and contributed to premature germ cell depletion. Transcriptomic profiling revealed a coordinated disruption of signaling pathways critical for spermatogonial stem cell maintenance, alongside genes involved in cell communication, ion homeostasis, cytoskeletal organization, and adhesion. Our findings suggest nphp4 is a key regulator of the testicular niche and highlight the utility of the medaka model in uncovering conserved mechanisms of infertility associated with cilia-related genes.<\/jats:p>","DOI":"10.1093\/reprod\/xaag027","type":"journal-article","created":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T12:33:59Z","timestamp":1772368439000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>nphp4<\/i>\n                    deficiency disrupts testicular homeostasis and impairs male fertility in medaka (\n                    <i>Oryzias latipes<\/i>\n                    )"],"prefix":"10.1093","volume":"171","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2813-0948","authenticated-orcid":false,"given":"Jingjie","family":"Liang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mariculture Breeding, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College of Jimei University , Xiamen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9128-8671","authenticated-orcid":false,"given":"Jiangling","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Breeding, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College of Jimei University , Xiamen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3492-274X","authenticated-orcid":false,"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Breeding, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College of Jimei University , Xiamen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3467-9608","authenticated-orcid":false,"given":"Manying","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Breeding, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College of Jimei University , Xiamen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4042-1832","authenticated-orcid":false,"given":"Ruimin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Breeding, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College of Jimei University , Xiamen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2148-3595","authenticated-orcid":false,"given":"Xiangrui","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Breeding, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College of Jimei University , Xiamen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4049-5468","authenticated-orcid":false,"given":"HaiQing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Breeding, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College of Jimei University , Xiamen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-2307","authenticated-orcid":false,"given":"Tiansheng","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mariculture Breeding, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College of Jimei University , Xiamen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"2026031903161598600_xaag027-B1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet (London, England)"},{"key":"2026031903161598600_xaag027-B2","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1111\/cge.12160","article-title":"NPHP4 mutation is 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