{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:18:10Z","timestamp":1793395090157,"version":"4.5.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Male factors contribute to 50% of infertility cases, with 20%\u201330% of cases being solely attributed to male infertility. Helicase for meiosis 1 (\n                    <jats:italic toggle=\"yes\">HFM1<\/jats:italic>\n                    ) plays a crucial role in ensuring proper crossover formation and synapsis of homologous chromosomes during meiosis, an essential process in gametogenesis.\n                    <jats:italic toggle=\"yes\">HFM1<\/jats:italic>\n                    gene mutations are associated with male infertility, particularly in cases of non-obstructive azoospermia and severe oligozoospermia. However, the effects of intracytoplasmic sperm injection (ICSI) in\n                    <jats:italic toggle=\"yes\">HFM1<\/jats:italic>\n                    -related infertility cases remain inadequately explored. This study identified novel biallelic\n                    <jats:italic toggle=\"yes\">HFM1<\/jats:italic>\n                    variants through whole-exome sequencing (WES) in a Chinese patient with severe oligozoospermia, which was confirmed by Sanger sequencing. The pathogenicity of these variants was assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting, which revealed a significant reduction in\n                    <jats:italic toggle=\"yes\">HFM1<\/jats:italic>\n                    mRNA and protein levels in spermatozoa compared to those in a healthy control. Transmission electron microscopy revealed morphological abnormalities in sperm cells, including defects in the head and flagellum. Despite these abnormalities, ICSI treatment resulted in a favorable fertility outcome for the patient, indicating that assisted reproductive techniques (ART) can be effective in managing\n                    <jats:italic toggle=\"yes\">HFM1<\/jats:italic>\n                    -related male infertility. These findings offer valuable insights into the management of such cases.\n                  <\/jats:p>","DOI":"10.4103\/aja20259","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T03:00:10Z","timestamp":1746414010000},"page":"751-756","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Novel biallelic HFM1 variants cause severe oligozoospermia with favorable intracytoplasmic sperm injection outcome"],"prefix":"10.4103","volume":"27","author":[{"given":"Liu","family":"Liu","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"},{"name":"Department of Computational Biology, School of Life Sciences, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Zhou","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Dong","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, School of Life Sciences, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"},{"name":"Shanghai JIAI Genetics and IVF Institute-China USA Center, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Xiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou 215002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Soong Ching Ling Institute of Maternity and Child Health, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Soong Ching Ling Institute of Maternity and Child Health, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"R1-20251103","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","article-title":"Fertility and infertility:definition and epidemiology","volume":"62","author":"Vander","year":"2018","journal-title":"Clin Biochem"},{"key":"R2-20251103","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.3390\/ijms21051728","article-title":"Molecular biology of spermatogenesis:novel targets of apparently idiopathic male infertility","volume":"21","author":"Cannarella","year":"2020","journal-title":"Int J Mol Sci"},{"key":"R3-20251103","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/humupd\/dmv020","article-title":"Teratozoospermia:spotlight on the main genetic actors in the human","volume":"21","author":"Coutton","year":"2015","journal-title":"Hum Reprod 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of male infertility \u2013present and future:a narrative review","volume":"14","author":"Sudhakar","year":"2021","journal-title":"J Hum Reprod Sci"},{"key":"R8-20251103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00439-020-02245-0","article-title":"Editorial for the special issue on the molecular genetics of male infertility","volume":"140","author":"Krausz","year":"2021","journal-title":"Hum Genet"},{"key":"R9-20251103","doi-asserted-by":"crossref","first-page":"R159","DOI":"10.1530\/REP-15-0261","article-title":"Genetics of male infertility:from research to clinic","volume":"150","author":"Krausz","year":"2015","journal-title":"Reproduction"},{"key":"R10-20251103","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1093\/humupd\/dmaa034","article-title":"Molecular genetics of infertility:loss-of-function mutations in humans and corresponding knockout\/mutated mice","volume":"27","author":"Jiao","year":"2021","journal-title":"Hum Reprod Update"},{"key":"R11-20251103","doi-asserted-by":"crossref","first-page":"435","DOI":"10.4103\/aja202272","article-title":"A novel homozygous loss-of-function mutation in RAD51AP2 induces male infertility with nonobstructive azoospermia","volume":"25","author":"Liu","year":"2023","journal-title":"Asian J Androl"},{"key":"R12-20251103","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4103\/aja202321","article-title":"The identification of AMZ2 as a candidate causative gene in a severe teratozoospermia patient characterized by vacuolated spermatozoa","volume":"26","author":"Liu","year":"2024","journal-title":"Asian J Androl"},{"key":"R13-20251103","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00438-024-02117-6","article-title":"Deleterious variant in FAM71D cause male infertility with asthenoteratospermia","volume":"299","author":"Zhu","year":"2024","journal-title":"Mol Genet Genomics"},{"key":"R14-20251103","article-title":"Whole-exome sequencing identifies ADGB as a novel causative gene for male infertility in humans:from motility to fertilization","author":"Gao","year":"2024","journal-title":"Andrology"},{"key":"R15-20251103","doi-asserted-by":"crossref","first-page":"e1003383","DOI":"10.1371\/journal.pgen.1003383","article-title":"Mouse HFM1\/Mer3 is required for crossover formation and complete synapsis of homologous chromosomes during meiosis","volume":"9","author":"Guiraldelli","year":"2013","journal-title":"PLoS Genet"},{"key":"R16-20251103","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1093\/humrep\/deac092","article-title":"Biallelic HFM1 variants cause non-obstructive azoospermia with meiotic arrest in humans by impairing crossover formation to varying degrees","volume":"37","author":"Xie","year":"2022","journal-title":"Hum Reprod"},{"key":"R17-20251103","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s41419-020-2697-4","article-title":"HFM1 participates in Golgi-associated spindle assembly and division in mouse oocyte meiosis","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis"},{"key":"R18-20251103","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40659-024-00518-w","article-title":"The crucial role of HFM1 in regulating FUS ubiquitination and localization for oocyte meiosis prophase I progression in mice","volume":"57","author":"Zhong","year":"2024","journal-title":"Biol Res"},{"key":"R19-20251103","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1080\/10425170600805433","article-title":"HFM1 the human homologue of yeast Mer3 encodes a putative DNA helicase expressed specifically in germ-line cells","volume":"17","author":"Tanaka","year":"2006","journal-title":"DNA Seq"},{"key":"R20-20251103","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ajhg.2022.01.011","article-title":"Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia","volume":"109","author":"Kherraf","year":"2022","journal-title":"Am J Hum Genet"},{"key":"R21-20251103","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1007\/s10815-023-02907-8","article-title":"A novel splicing mutation in helicase for meiosis 1 leads to non-obstructive azoospermia","volume":"40","author":"Yao","year":"2023","journal-title":"J Assist Reprod Genet"},{"key":"R22-20251103","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s10815-022-02433-z","article-title":"Identification of a new splice-acceptor mutation in HFM1 and functional analysis through molecular docking in nonobstructive azoospermia","volume":"39","author":"Saebnia","year":"2022","journal-title":"J Assist Reprod Genet"},{"key":"R23-20251103","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s12958-021-00815-z","article-title":"Novel variants in helicase for meiosis 1 lead to male infertility due to non-obstructive azoospermia","volume":"19","author":"Tang","year":"2021","journal-title":"Reprod Biol Endocrinol"},{"key":"R24-20251103","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11427-016-0274-9","article-title":"Association analysis between HFM1 variations and idiopathic azoospermia or severe oligozoospermia in Chinese men","volume":"60","author":"Zhang","year":"2017","journal-title":"Sci China Life Sci"},{"key":"R25-20251103","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2010","journal-title":"Hum Reprod Update"},{"key":"R26-20251103","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp:an ultra-fast all-in-one FASTQ 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infertility","volume":"108","author":"Liu","year":"2021","journal-title":"Am J Hum Genet"},{"key":"R33-20251103","doi-asserted-by":"crossref","first-page":"hoae003","DOI":"10.1093\/hropen\/hoae003","article-title":"Bi-allelic variants in DNAH3 cause male infertility with asthenoteratozoospermia in humans and mice","author":"Meng","year":"2024","journal-title":"Hum Reprod Open. 2024"},{"key":"R34-20251103","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.3390\/cells10071594","article-title":"Novel mutations in X-linked, USP26-induced asthenoteratozoospermia and male infertility","volume":"10","author":"Liu","year":"2021","journal-title":"Cells"},{"key":"R35-20251103","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jgg.2022.12.004","article-title":"A homozygous frameshift mutation in ADAD2 causes male infertility with spermatogenic impairments","volume":"50","author":"Tian","year":"2023","journal-title":"J Genet 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Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja20259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:40:55Z","timestamp":1787838055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja20259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/aja20259","relation":{},"ISSN":["1745-7262","1008-682X"],"issn-type":[{"value":"1745-7262","type":"print"},{"value":"1008-682X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,2]]},"assertion":[{"value":"2024-09-19","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-14","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}