{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:44:55Z","timestamp":1785739495068,"version":"3.56.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82325021"],"award-info":[{"award-number":["82325021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32130029"],"award-info":[{"award-number":["32130029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201767"],"award-info":[{"award-number":["82201767"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China","award":["JYB2025XDXM508"],"award-info":[{"award-number":["JYB2025XDXM508"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Are there new genetic factors responsible for male infertility characterized by fertilization defects despite normal sperm motility?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>We identified the novel pathogenetic gene actin-related protein T3 (ACTRT3) as one of primary causes for male infertility characterized by fertilization defects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>To date, only a few genes have been reported to be responsible for fertilization defects in male infertility despite normal sperm motility. ACTRT3, as one of the actin-related proteins, is specifically expressed highly in murine testes and interacts with the protein Profilin3 to form a testis-specific complex during spermatogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>The ACTRT3 variants were identified by whole-exome sequencing in a cohort of 248 infertile couples characterized by fertilization defects (fertilization rate\u2009\u2264\u200930% in their IVF\/ICSI attempts) despite normal sperm concentration (\u226515 \u00d7 106\/ml) and normal motility (progressive motility \u226532%; motility of PR (progressive)+NP (non-progressive) \u226540%). Thirty-six hours after cell transfection, immunoprecipitation was performed to detect the interaction between ACTRT3 and actin-like 7A (ACTL7A)\/phospholipase C zeta 1 (PLCZ1) (n\u2009=\u20093 biological replicates). A knock-in (KI) mouse model was generated by CRISPR-Cas9. Sexually mature males (10\u2009weeks old) were used for fertility testing (n\u2009=\u20093 mice per group, lasts 6\u20138\u2009months), semen parameter analysis (n\u2009=\u20093 mice per group), western blot (n\u2009=\u20093 biological replicates), immunofluorescence (n\u2009=\u20093 biological replicates), IVF (n\u2009\u2265\u20093 biological replicates), ICSI (n\u2009=\u20093 biological replicates), scanning electron microscopy (SEM, n\u2009=\u20093 mice per group), transmission electron microscopy (TEM, n\u2009=\u20093 mice per group), Ca2+ oscillations (n\u2009\u2265\u20093 biological replicates), and other functional assays between 2022 and 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>The ACTRT3 variants were identified by whole-exome sequencing and confirmed by Sanger sequencing. ACTRT3 KI mouse was constructed to discover the pathogenic mechanism. We first checked ultrastructure of the sperm through periodic acid-schiff staining, SEM, and TEM. Western blotting, immunofluorescence, and immunoprecipitation were further performed to clarify the molecular mechanism of the ACTRT3 variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>We identified compound-heterozygous (NM_032487.5: c. C41G (p. Ser14Trp) and c. C687delA (p. Lys229fs)) and homozygous variants (NM_032487.5: c.712C&amp;gt;T (p. Gln238Ter)) in ACTRT3 in two infertile males, and functional studies in transgenic KI mouse models confirmed the pathogenicity of the Actrt3 variants. Defects in ACTRT3 caused decreased protein levels of ACTL7A and disrupted localization of PLCZ1 in sperm, which resulted in acrosome detachment, further impacted the binding between sperm and the zona pellucida of oocytes and caused fertilization failure. In addition, sperm with defective ACTRT3 cannot initiate calcium oscillations, which leads to embryo arrest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LARGE SCALE DATA<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>More cases are needed to confirm the genetic contribution of ACTRT3 variants to male infertility. In addition, it will be more persuasive and informative by adding the rescue experiments of artificial oocyte activation through SrCl2 which is used to active calcium ion oscillation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Our findings suggest the causal relationship between ACTRT3 variants and male infertility caused by fertilization defects, and partially revealing the pathological mechanisms of ACTRT3 variants. This provides new insights into the understanding of male infertility due to fertilization problems and provides references for future clinical treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This work was supported by the National Natural Science Foundation of China (82325021, 32130029, and 82201767) and the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China (No. JYB2025XDXM508).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>N\/A<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deag097","type":"journal-article","created":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T11:34:05Z","timestamp":1780832045000},"page":"1350-1366","source":"Crossref","is-referenced-by-count":0,"title":["Pathogenic variants in\n                    <i>ACTRT3<\/i>\n                    lead to male infertility characterized by fertilization defects"],"prefix":"10.1093","volume":"41","author":[{"given":"Hongying","family":"Zhu","sequence":"first","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Shi","sequence":"additional","affiliation":[{"name":"Northwest Women\u2019s and Children\u2019s Hospital Reproductive Medicine Center, , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-3382","authenticated-orcid":false,"given":"Feiyang","family":"Diao","sequence":"additional","affiliation":[{"name":"Jiangsu Province Hospital Clinical Center of Reproductive Medicine, , Nanjing, Jiangsu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9528-180X","authenticated-orcid":false,"given":"Ronggui","family":"Qu","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-3439","authenticated-orcid":false,"given":"Ruyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Assisted Reproduction, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanzi","family":"Shi","sequence":"additional","affiliation":[{"name":"Northwest Women\u2019s and Children\u2019s Hospital Reproductive Medicine Center, , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4725-883X","authenticated-orcid":false,"given":"Zhihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-1818","authenticated-orcid":false,"given":"Weijie","family":"Wang","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9921-2155","authenticated-orcid":false,"given":"Biaobang","family":"Chen","sequence":"additional","affiliation":[{"name":"NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"He","sequence":"additional","affiliation":[{"name":"Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3400-0434","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-6415","authenticated-orcid":false,"given":"Jian","family":"Mu","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9895-1394","authenticated-orcid":false,"given":"Qing","family":"Sang","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics, Children\u2019s Hospital of Fudan University, Institutes of Biomedical Sciences, The State Key Laboratory of Genetic Engineering, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"2026080301512797300_deag097-B1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1095\/biolreprod.110.089466","article-title":"Molecular cloning and characterization of phospholipase C zeta in equine sperm and testis reveals species-specific differences in expression of catalytically active protein","volume":"85","author":"Bedford-Guaus","year":"2011","journal-title":"Biol Reprod"},{"key":"2026080301512797300_deag097-B2","doi-asserted-by":"crossref","DOI":"10.1242\/dev.176966","article-title":"The molecular mechanisms mediating mammalian fertilization","volume":"146","author":"Bhakta","year":"2019","journal-title":"Development (Cambridge, England)"},{"key":"2026080301512797300_deag097-B3","doi-asserted-by":"crossref","first-page":"11543","DOI":"10.1074\/jbc.M110.171264","article-title":"Molecular recognition of the Tes LIM2-3 domains by the actin-related protein Arp7A","volume":"286","author":"Bo\u00ebda","year":"2011","journal-title":"J Biol Chem"},{"key":"2026080301512797300_deag097-B4","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 Update"},{"key":"2026080301512797300_deag097-B5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ajhg.2018.12.013","article-title":"Bi-allelic mutations in ARMC2 lead to severe astheno-teratozoospermia due to sperm flagellum malformations in humans and mice","volume":"104","author":"Coutton","year":"2019","journal-title":"Am J Hum Genet"},{"key":"2026080301512797300_deag097-B6","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/316541a0","article-title":"Phorbol ester and sperm activate mouse oocytes by inducing sustained oscillations in cell Ca2+","volume":"316","author":"Cuthbertson","year":"1985","journal-title":"Nature"},{"key":"2026080301512797300_deag097-B7","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ajhg.2021.02.004","article-title":"Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice","volume":"108","author":"Dai","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2026080301512797300_deag097-B8","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1086\/521314","article-title":"Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia","volume":"81","author":"Dam","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2026080301512797300_deag097-B9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41572-023-00459-w","article-title":"Male infertility","volume":"9","author":"Eisenberg","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"2026080301512797300_deag097-B10","first-page":"3167","article-title":"Homozygous deletion of SUN5 in three men with decapitated spermatozoa","volume":"26","author":"Elkhatib","year":"2017","journal-title":"Hum Mol Genet"},{"key":"2026080301512797300_deag097-B11","doi-asserted-by":"crossref","DOI":"10.1093\/molehr\/gaad005","article-title":"Testis-specific actin-like 7A (ACTL7A) is an indispensable protein for subacrosomal-associated F-actin formation, acrosomal anchoring, and male fertility","volume":"29","author":"Ferrer","year":"2023","journal-title":"Mol Human Reprod"},{"key":"2026080301512797300_deag097-B12","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1093\/humrep\/deab200","article-title":"Genetic diagnosis, sperm phenotype and ICSI outcome in case of severe asthenozoospermia with multiple morphological abnormalities of the flagellum","volume":"36","author":"Ferreux","year":"2021","journal-title":"Hum Reprod (Oxford, England)"},{"key":"2026080301512797300_deag097-B13","doi-asserted-by":"crossref","first-page":"e13459","DOI":"10.1111\/and.13459","article-title":"Globozoospermia syndrome: an update","volume":"52","author":"Fesahat","year":"2020","journal-title":"Andrologia"},{"key":"2026080301512797300_deag097-B14","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1126\/science.1059042","article-title":"Requirement of phospholipase Cdelta4 for the zona pellucida-induced acrosome reaction","volume":"292","author":"Fukami","year":"2001","journal-title":"Science"},{"key":"2026080301512797300_deag097-B15","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3390\/ijms25010285","article-title":"Overdue calcium oscillation causes polyspermy but possibly permits normal development in mouse eggs","volume":"25","author":"Fukuoka","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026080301512797300_deag097-B16","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/gim.2016.225","article-title":"A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes","volume":"19","author":"Gershoni","year":"2017","journal-title":"Genet Med"},{"key":"2026080301512797300_deag097-B17","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1093\/humrep\/den280","article-title":"The pattern of localization of the putative oocyte activation factor, phospholipase Czeta, in uncapacitated, capacitated, and ionophore-treated human spermatozoa","volume":"23","author":"Grasa","year":"2008","journal-title":"Hum Reprod (Oxford, England)"},{"key":"2026080301512797300_deag097-B18","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1242\/dev.150227","article-title":"PLC\u03b6 is the physiological trigger of the Ca2+ oscillations that induce embryogenesis in mammals but conception can occur in its absence","volume":"144","author":"Hachem","year":"2017","journal-title":"Development (Cambridge, England)"},{"key":"2026080301512797300_deag097-B19","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1016\/j.febslet.2008.07.058","article-title":"Nuclear localization of profilin III-ArpM1 complex in mouse spermiogenesis","volume":"582","author":"Hara","year":"2008","journal-title":"FEBS Lett"},{"key":"2026080301512797300_deag097-B20","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1006\/excr.2002.5603","article-title":"Novel actin-related proteins Arp-T1 and Arp-T2 as components of the cytoskeletal calyx of the mammalian sperm head","volume":"279","author":"Heid","year":"2002","journal-title":"Exp Cell Res"},{"key":"2026080301512797300_deag097-B21","first-page":"463","article-title":"Upstream or swim up processing technique: which one is more effective to select human sperm with high chromatin integrity","volume":"16","author":"Heidari","year":"2018","journal-title":"Int J Reprod Biomed"},{"key":"2026080301512797300_deag097-B22","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1093\/humrep\/dep207","article-title":"Reduced amounts and abnormal forms of phospholipase C zeta (PLCzeta) in spermatozoa from infertile men","volume":"24","author":"Heytens","year":"2009","journal-title":"Hum Reprod (Oxford, England)"},{"key":"2026080301512797300_deag097-B23","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1095\/biolreprod.108.067801","article-title":"Difference in Ca2+ oscillation-inducing activity and nuclear translocation ability of PLCZ1, an egg-activating sperm factor candidate, between mouse, rat, human, and medaka fish","volume":"78","author":"Ito","year":"2008","journal-title":"Biol Reprod"},{"key":"2026080301512797300_deag097-B25","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":"2026080301512797300_deag097-B26","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s10815-020-01748-z","article-title":"Increasing associations between defects in phospholipase C zeta and conditions of male infertility: not just ICSI failure?","volume":"37","author":"Kashir","year":"2020","journal-title":"J Assist Reprod Genet"},{"key":"2026080301512797300_deag097-B27","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1093\/humupd\/dmq018","article-title":"Oocyte activation, phospholipase C zeta and human infertility","volume":"16","author":"Kashir","year":"2010","journal-title":"Hum Reprod Update"},{"key":"2026080301512797300_deag097-B28","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4103\/aja.aja_67_20","article-title":"Advancing male age differentially alters levels and localization patterns of PLCzeta in sperm and testes from different mouse strains","volume":"23","author":"Kashir","year":"2021","journal-title":"Asian J Androl"},{"key":"2026080301512797300_deag097-B29","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.ajhg.2018.07.014","article-title":"A homozygous ancestral SVA-insertion-mediated deletion in WDR66 induces multiple morphological abnormalities of the sperm flagellum and male infertility","volume":"103","author":"Kherraf","year":"2018","journal-title":"Am J Hum Genet"},{"key":"2026080301512797300_deag097-B30","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/cge.13604","article-title":"Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations","volume":"96","author":"Kherraf","year":"2019","journal-title":"Clin Genet"},{"key":"2026080301512797300_deag097-B31","doi-asserted-by":"crossref","DOI":"10.1242\/dev.205283","article-title":"Actin-related protein T3 is required for acrosome biogenesis and sperm function in mice","volume":"153","author":"Kovacevic","year":"2026","journal-title":"Development (Cambridge, England)"},{"key":"2026080301512797300_deag097-B32","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1007\/s10815-024-03171-0","article-title":"Homozygous ACTL9 mutations cause irregular mitochondrial sheath arrangement and abnormal flagellum assembly in spermatozoa and male infertility","volume":"41","author":"Li","year":"2024","journal-title":"J Assist Reprod Genet"},{"key":"2026080301512797300_deag097-B33","doi-asserted-by":"crossref","first-page":"1193248","DOI":"10.3389\/fcell.2023.1193248","article-title":"Novel mutations in PLCZ1 lead to early embryonic arrest as a male factor","volume":"11","author":"Lin","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"2026080301512797300_deag097-B34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/humrep\/den334","article-title":"Enhancement of sperm-zona pellucida (ZP) binding capacity by activation of protein kinase A and C pathways in certain infertile men with defective sperm-ZP binding","volume":"24","author":"Liu","year":"2009","journal-title":"Hum Reprod (Oxford, England)"},{"key":"2026080301512797300_deag097-B35","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/aja.2010.47","article-title":"A newly discovered mutation in PICK1 in a human with globozoospermia","volume":"12","author":"Liu","year":"2010","journal-title":"Asian J Androl"},{"key":"2026080301512797300_deag097-B36","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s10815-015-0445-y","article-title":"Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia","volume":"32","author":"Maor-Sagie","year":"2015","journal-title":"J Assist Reprod Genet"},{"key":"2026080301512797300_deag097-B37","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/S0140-6736(03)14845-3","article-title":"Azoospermia in patients heterozygous for a mutation in SYCP3","volume":"362","author":"Miyamoto","year":"2003","journal-title":"Lancet (London, England)"},{"key":"2026080301512797300_deag097-B38","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1530\/REP-11-0073","article-title":"Pre-treatment of sperm reduces success of ICSI in the pig","volume":"142","author":"Nakai","year":"2011","journal-title":"Reproduction (Cambridge, England)"},{"key":"2026080301512797300_deag097-B39","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1111\/andr.12378","article-title":"Next-generation sequencing for patients with non-obstructive azoospermia: implications for significant roles of monogenic\/oligogenic mutations","volume":"5","author":"Nakamura","year":"2017","journal-title":"Andrology"},{"key":"2026080301512797300_deag097-B40","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1002\/mrd.22262","article-title":"The novel, actin-like protein Tact3 is expressed in rodent testicular haploid germ cells","volume":"80","author":"Oh","year":"2013","journal-title":"Mol Reprod Dev"},{"key":"2026080301512797300_deag097-B41","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/humrep\/dez246","article-title":"Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia","volume":"35","author":"Oud","year":"2020","journal-title":"Hum Reprod (Oxford, England)"},{"key":"2026080301512797300_deag097-B42","doi-asserted-by":"crossref","first-page":"101479","DOI":"10.1016\/j.beem.2020.101479","article-title":"Genetic mutations contributing to non-obstructive azoospermia","volume":"34","author":"Pe\u00f1a","year":"2020","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"2026080301512797300_deag097-B43","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1126\/science.adf7760","article-title":"Understanding the genetics of human infertility","volume":"380","author":"Sang","year":"2023","journal-title":"Science"},{"key":"2026080301512797300_deag097-B44","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/asj.12044","article-title":"Molecular characteristics of horse phospholipase C zeta (PLC\u03b6)","volume":"84","author":"Sato","year":"2013","journal-title":"Anim Sci J"},{"key":"2026080301512797300_deag097-B45","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1146\/annurev.cellbio.15.1.341","article-title":"Actin-related proteins","volume":"15","author":"Schafer","year":"1999","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2026080301512797300_deag097-B46","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/cge.13140","article-title":"TSGA10 is a novel candidate gene associated with acephalic spermatozoa","volume":"93","author":"Sha","year":"2018","journal-title":"Clin Genet"},{"key":"2026080301512797300_deag097-B47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.gene.2018.01.035","article-title":"Genetic contribution of SUN5 mutations to acephalic spermatozoa in Fujian China","volume":"647","author":"Sha","year":"2018","journal-title":"Gene"},{"key":"2026080301512797300_deag097-B48","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202102146","article-title":"The cell biology of fertilization: gamete attachment and fusion","volume":"220","author":"Siu","year":"2021","journal-title":"J Cell Biol"},{"key":"2026080301512797300_deag097-B49","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3390\/biom14030359","article-title":"Molecular mechanism of oocyte activation in mammals: past, present, and future directions","volume":"14","author":"Sugita","year":"2024","journal-title":"Biomolecules"},{"key":"2026080301512797300_deag097-B50","doi-asserted-by":"crossref","first-page":"pdb.prot094508","DOI":"10.1101\/pdb.prot094508","article-title":"In vitro fertilization in mice","volume":"2017","author":"Taft","year":"2017","journal-title":"Cold Spring Harb Protoc"},{"key":"2026080301512797300_deag097-B51","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1095\/biolreprod.103.015867","article-title":"Novel actin-like proteins T-ACTIN 1 and T-ACTIN 2 are differentially expressed in the cytoplasm and nucleus of mouse haploid germ cells","volume":"69","author":"Tanaka","year":"2003","journal-title":"Biol Reprod"},{"key":"2026080301512797300_deag097-B52","doi-asserted-by":"crossref","first-page":"749559","DOI":"10.3389\/fcell.2021.749559","article-title":"Loss of Profilin3 impairs spermiogenesis by affecting acrosome biogenesis, autophagy, manchette development and mitochondrial organization","volume":"9","author":"Umer","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2026080301512797300_deag097-B53","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1093\/humrep\/deab228","article-title":"Novel bi-allelic variants in ACTL7A are associated with male infertility and total fertilization failure","volume":"36","author":"Wang","year":"2021","journal-title":"Hum Reprod (Oxford, England)"},{"key":"2026080301512797300_deag097-B54","doi-asserted-by":"crossref","first-page":"231","DOI":"10.4103\/aja202198","article-title":"Genetic pathogenesis of acephalic spermatozoa syndrome: past, present, and future","volume":"24","author":"Wang","year":"2022","journal-title":"Asian J Androl"},{"key":"2026080301512797300_deag097-B55","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nrm1149","article-title":"Calcium signalling during embryonic development","volume":"4","author":"Webb","year":"2003","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026080301512797300_deag097-B56","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1152\/physrev.00023.2005","article-title":"Calcium at fertilization and in early development","volume":"86","author":"Whitaker","year":"2006","journal-title":"Physiol Rev"},{"key":"2026080301512797300_deag097-B57","doi-asserted-by":"crossref","first-page":"eaaz4796","DOI":"10.1126\/sciadv.aaz4796","article-title":"Disruption in ACTL7A causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest","volume":"6","author":"Xin","year":"2020","journal-title":"Sci Adv"},{"key":"2026080301512797300_deag097-B58","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/molehr\/gau099","article-title":"Dpy19l2-deficient globozoospermic sperm display altered genome packaging and DNA damage that compromises the initiation of embryo development","volume":"21","author":"Yassine","year":"2015","journal-title":"Mol Hum Reprod"},{"key":"2026080301512797300_deag097-B59","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/molehr\/gar057","article-title":"Association of mutations in the zona pellucida binding protein 1 (ZPBP1) gene with abnormal sperm head morphology in infertile men","volume":"18","author":"Yatsenko","year":"2012","journal-title":"Mol Hum Reprod"},{"key":"2026080301512797300_deag097-B60","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1530\/rep.1.01018","article-title":"Molecular cloning, testicular postnatal expression, and oocyte-activating potential of porcine phospholipase Czeta","volume":"132","author":"Yoneda","year":"2006","journal-title":"Reproduction (Cambridge, England)"},{"key":"2026080301512797300_deag097-B61","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1530\/REP-07-0259","article-title":"Release of phospholipase C zetaand [Ca2+]i oscillation-inducing activity during mammalian fertilization","volume":"134","author":"Yoon","year":"2007","journal-title":"Reproduction (Cambridge, England)"},{"key":"2026080301512797300_deag097-B62","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1172\/JCI36942","article-title":"Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development","volume":"118","author":"Yoon","year":"2008","journal-title":"J Clin Invest"},{"key":"2026080301512797300_deag097-B63","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/humrep\/deae031","article-title":"Deletion of ACTRT1 is associated with male infertility as sperm acrosomal ultrastructural defects and fertilization failure in human","volume":"39","author":"Zhang","year":"2024","journal-title":"Hum Reprod (Oxford, England)"},{"key":"2026080301512797300_deag097-B64","doi-asserted-by":"crossref","DOI":"10.1242\/dev.200489","article-title":"Loss of perinuclear theca ACTRT1 causes acrosome detachment and severe male subfertility in mice","volume":"149","author":"Zhang","year":"2022","journal-title":"Development (Cambridge, England)"},{"key":"2026080301512797300_deag097-B65","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12958-023-01130-5","article-title":"Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex","volume":"21","author":"Zhang","year":"2023","journal-title":"Reprod Biol Endocrinol"},{"key":"2026080301512797300_deag097-B66","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/cge.14293","article-title":"Novel variants in ACTL7A and PLCZ1 are associated with male infertility and total fertilization failure","volume":"103","author":"Zhao","year":"2023","journal-title":"Clin Genet"},{"key":"2026080301512797300_deag097-B67","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bbrc.2022.07.065","article-title":"Actl7a deficiency in mice leads to male infertility and fertilization failure","volume":"623","author":"Zhou","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"2026080301512797300_deag097-B68","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.ajhg.2016.11.002","article-title":"Biallelic SUN5 mutations cause autosomal-recessive acephalic spermatozoa syndrome","volume":"99","author":"Zhu","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2026080301512797300_deag097-B69","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1093\/humrep\/den193","article-title":"Mutations in dynein genes in patients affected by isolated non-syndromic asthenozoospermia","volume":"23","author":"Zuccarello","year":"2008","journal-title":"Hum Reprod (Oxford, England)"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/41\/8\/1350\/68577358\/deag097.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/41\/8\/1350\/68577358\/deag097.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:51:43Z","timestamp":1785736303000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/41\/8\/1350\/8713370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":68,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,6,22]]},"published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deag097","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,6,22]]}}}