{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:47:05Z","timestamp":1785829625634,"version":"3.56.0"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["25TS1400900"],"award-info":[{"award-number":["25TS1400900"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["23JC1403803"],"award-info":[{"award-number":["23JC1403803"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501934"],"award-info":[{"award-number":["82501934"]}],"id":[{"id":"10.13039\/501100001809","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>\n                      Spermiogenesis is a highly specialized differentiation process involving by extensive nuclear remodeling and cytoplasmic reorganization. Disruption of these events is a major cause of male infertility, however the genetic determinants underlying human spermiogenic failure remain incompletely understood.\n                      <jats:italic>NUP210L<\/jats:italic>\n                      , which encodes a testis\u2010enriched nucleoporin, has recently been implicated in male infertility, although direct evidence in humans is limited and murine models do not fully recapitulate the human phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To investigate the genetic basis and spermiogenic consequences of a homozygous\n                      <jats:italic>NUP210L<\/jats:italic>\n                      variant in a patient with severe oligoasthenoteratozoospermia (OAT), and to evaluate its impact on fertilization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>A consanguineous family with an affected male proband was studied. Whole\u2010exome sequencing followed by Sanger validation was performed to identify the causative variant. Comprehensive sperm analyses, including light and transmission electron microscopy, immunofluorescence, Western blotting, and chromomycin A3 staining, were conducted to assess ultrastructure, protein localization, and chromatin remodeling. Fertilization outcomes of intracytoplasmic sperm injection (ICSI) with or without artificial oocyte activation (AOA) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A homozygous in\u2010frame deletion in\n                      <jats:italic>NUP210L<\/jats:italic>\n                      (c.1501_1503del, p.Ser501del) was identified. Patient sperm exhibited marked spermiogenic defects, including impaired chromatin condensation, acrosomal abnormalities, mitochondrial sheath disorganization, and fibrous sheath dysplasia. Although NUP210L protein levels were preserved, immunofluorescence revealed abnormal accumulation and mislocalization, suggesting functional impairment rather than loss of expression. Chromomycin A3 staining indicated significant histone retention, consistent with defective nuclear remodeling. Notably, the sperm\u2010specific oocyte activation factor PLC\u03b6 was undetectable, consistent with total fertilization failure (TFF) following conventional ICSI. In contrast, ICSI combined with AOA successfully restored fertilization and enabled blastocyst development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identifies a homozygous\n                      <jats:italic>NUP210L<\/jats:italic>\n                      variant associated with severe spermiogenic defects and impaired sperm function. The findings support a role for NUP210L in human spermiogenesis that is not fully recapitulated in murine models. The successful rescue of fertilization by AOA further suggests that\n                      <jats:italic>NUP210L<\/jats:italic>\n                      \u2010related defects are associated with impaired oocyte activation, providing human\u2010based evidence that nucleoporin dysfunction contributes to male infertility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70330","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:05:14Z","timestamp":1785827114000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Homozygous\n                    <i>NUP210L<\/i>\n                    Variant Is Associated With Severe Defects in Human Spermiogenesis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5913-5491","authenticated-orcid":false,"given":"Yisi","family":"Sun","sequence":"first","affiliation":[{"name":"Pharmacy School, Fudan University; Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies (SIBPT), Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowu","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Ji Ai Genetics &amp; IVF Institute, Obstetrics &amp; Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-1793","authenticated-orcid":false,"given":"Yini","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Ji Ai Genetics &amp; IVF Institute, Obstetrics &amp; Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases Fudan University Shanghai China"},{"name":"Department of Obstetrics and Gynecology, Reproductive Medicine Center Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Health Science and Engineering University of Shanghai for Science and Technology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlun","family":"Song","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center Affiliated Hospital of Youjiang Medical University for Nationalities  Baise China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Pharmacy School, Fudan University; Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of 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