{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:02:31Z","timestamp":1783008151915,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1003602"],"award-info":[{"award-number":["2018YFC1003602"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The process of spermatogenesis is a complex and delicate process that is still not fully understood. In this study, we examined the role of fatty acid oxidase 3\u2010hydroxy acyl CoA dehydrogenase (HADH) in maintaining normal spermatogenesis in mice. In male mice, ablation of the\n                    <jats:italic>Hadh<\/jats:italic>\n                    gene using CRISPR\/Cas9 technology arrested spermatocyte meiosis, increased multinucleated giant germ cells and vacuoles in seminiferous tubules, and accompanied with acrosomal dysplasia.\n                    <jats:italic>Hadh<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    male mice showed the typical features of oligoasthenoteratozoospermia (OAT), including decreased sperm concentration and motility and increased sperm abnormalities. Next, we explored the molecular events in the testes of the mutant mice. We found fatty acids accumulated in the testis of\n                    <jats:italic>Hadh<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. And also, inflammatory factors TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106 were significantly increased, apoptosis\u2010related protein Bcl\u20102 was decreased, and Bax and cleaved\u2010Caspase3 were increased in\n                    <jats:italic>Hadh<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    male mice testis. After using etanercept, a specific inhibitor of TNF\u2010\u03b1, testis injury caused by\n                    <jats:italic>Hadh<\/jats:italic>\n                    knockout was significantly alleviated, the sperm quality and motility were improved, and germ cell apoptosis was reduced. So our study demonstrated that\n                    <jats:italic>Hadh<\/jats:italic>\n                    deletion caused an increase in fatty acids. The accumulated fatty acids further induced testicular inflammation and germ cell apoptosis through the TNF\u2010\u03b1\/Bcl\u20102 signaling pathway, finally resulting in OAT in the\n                    <jats:italic>Hadh<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Inhibiting TNF\u2010\u03b1 may be used as a new treatment approach for testicular inflammation and OAT.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201144r","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T04:14:40Z","timestamp":1668744880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>Hadh<\/i>\n                    deficiency induced oligoasthenoteratozoospermia through the\n                    <scp>TNF<\/scp>\n                    \u2010\u03b1\/Bcl\u20102 pathway in male mice"],"prefix":"10.1096","volume":"36","author":[{"given":"Haixia","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyue","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongzhuang","family":"Wen","sequence":"additional","affiliation":[{"name":"Medical Science and Technology Innovation Center Shandong First Medical University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6619-7107","authenticated-orcid":false,"given":"Jiangang","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology Shandong University  Jinan China"},{"name":"Medical Science and Technology Innovation Center Shandong First Medical University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S241099"},{"issue":"1","key":"e_1_2_10_3_1","first-page":"12","article-title":"Disorders of spermatogenesis: perspectives for novel genetic diagnostics after 20\u2009years of unchanged routine","volume":"30","author":"Tuttelmann F","year":"2018","journal-title":"Med Genet"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2235-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03755-z"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087816"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.111.012989"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-021-00721-0"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1370107"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(02)00060-8"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.133.1.8319585"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.133.6.8243279"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-015-0835-8"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19348"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-010-9148-y"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3134"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105045"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1109\/JTEHM.2021.3104966"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.789923"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2021.08.008"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/00368504211011344"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112178"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.13.5016"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199686"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.6"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.3.1041-1053.2005"},{"issue":"10","key":"e_1_2_10_27_1","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1242\/jcs.202721","article-title":"TSSK6 is required for gammaH2AX formation and the histone\u2010to\u2010protamine transition during spermiogenesis","volume":"130","author":"Jha KN","year":"2017","journal-title":"J Cell Sci"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.077"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(97)01215-4"},{"issue":"4","key":"e_1_2_10_30_1","first-page":"389","article-title":"Bcl\u20102 family proteins and apoptosis","volume":"34","author":"Fu YF","year":"2002","journal-title":"Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai)"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00754"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-016-3769-2"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2020.06.003"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09356"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.1986.tb01729.x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.1993.tb02733.x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2020.101473"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.012375"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa003005"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod67.1.269"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26668"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq213"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-013-9642-4"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7262.2006.00123.x"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2017.07.013"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2020.114748"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.725933"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2019.1566456"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.59"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.114.006940"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.04.024"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10040432"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1412s109"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300298"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202201144R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202201144R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202201144R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:16:16Z","timestamp":1761700576000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202201144R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":53,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1096\/fj.202201144R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202201144r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,18]]},"assertion":[{"value":"2022-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22661"}}