{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:16:07Z","timestamp":1783016167291,"version":"3.54.6"},"reference-count":13,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"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":["82471650"],"award-info":[{"award-number":["82471650"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017513","name":"Sichuan Association for Science and Technology","doi-asserted-by":"publisher","award":["2024YFFK0267"],"award-info":[{"award-number":["2024YFFK0267"]}],"id":[{"id":"10.13039\/100017513","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fertilization failure remains a major cause of infertility and poor outcomes in assisted reproductive technology, yet the underlying genetic mechanisms are incompletely understood. In this study, we investigated two unrelated infertile men presenting with macrozoospermia and recurrent fertilization failure following intracytoplasmic sperm injection (ICSI). Whole\u2010exome sequencing identified biallelic variants in\n                    <jats:italic>NUP210L<\/jats:italic>\n                    , including a homozygous variant (c.3361C&gt;T) in one patient and compound heterozygous variants (c.3853C&gt;G and c.2965G&gt;T) in another, which were confirmed by Sanger sequencing and predicted to be deleterious. Functional analyses revealed markedly reduced NUP210L expression in the patients' spermatozoa. Morphological assessment by Papanicolaou staining and scanning electron microscopy showed enlarged and irregular sperm heads accompanied by multiple flagella, while severely impaired chromatin condensation was observed under transmission electron microscopy. Consistently, immunofluorescence demonstrated significantly decreased expression of the protamines PRM1 and PRM2, indicating disruption of the histone\u2010to\u2010protamine transition during spermatogenesis. Expression analyses further revealed that NUP210L is predominantly expressed in spermatids in both human and mouse testes, supporting its role in late spermatogenic stages. Collectively, these findings provide evidence linking\n                    <jats:italic>NUP210L<\/jats:italic>\n                    deficiency to impaired chromatin condensation and fertilization failure, thereby expanding the genetic spectrum of fertilization failure and offering crucial insights for genetic diagnosis and clinical management in assisted reproduction.\n                  <\/jats:p>","DOI":"10.1111\/cge.70175","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:56:01Z","timestamp":1777510561000},"page":"254-259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <scp>\n                      <i>NUP210L<\/i>\n                    <\/scp>\n                    Variants Cause Fertilization Failure and Male Infertility in Humans"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3418-4394","authenticated-orcid":false,"given":"Keyu","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital Sichuan University  Chengdu China"},{"name":"West China School of Medicine Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital Sichuan University  Chengdu China"},{"name":"West China School of Medicine Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yantong","family":"Zheng","sequence":"additional","affiliation":[{"name":"West China School of Medicine Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingteng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproduction Medical Center, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6346-1002","authenticated-orcid":false,"given":"Ying","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital Sichuan University  Chengdu China"},{"name":"NHC Key Laboratory of Chronobiology Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.018"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102208"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz4796"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.02.004"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200330"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.015115"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2017.0040"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa329"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14468"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaf194"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2006-0332"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/521314"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adv5189"}],"container-title":["Clinical 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