{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:30:50Z","timestamp":1783488650870,"version":"3.55.0"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004070","name":"Khalifa University","doi-asserted-by":"publisher","award":["FSU-2023-015"],"award-info":[{"award-number":["FSU-2023-015"]}],"id":[{"id":"10.13039\/501100004070","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Healthcare Research Fellowship Award","award":["HF-14-16"],"award-info":[{"award-number":["HF-14-16"]}]},{"DOI":"10.13039\/100012068","name":"Health and Care Research Wales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012068","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science, Technology, and Innovation plan","award":["15-MED4186-20"],"award-info":[{"award-number":["15-MED4186-20"]}]},{"DOI":"10.13039\/501100004919","name":"King Abdulaziz City for Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004919","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Are sperm phospholipase C zeta (PLC\u03b6) profiles linked to the quality of embryogenesis and pregnancy?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>Sperm PLC\u03b6 levels in both mouse and humans correlate with measures of ideal embryogenesis whereby minimal levels seem to be required to result in successful pregnancy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>While causative factors underlying male infertility are multivariable, cases are increasingly associated with the efficacy of oocyte activation, which in mammals occurs in response to specific profiles of calcium (Ca2+) oscillations driven by sperm-specific PLC\u03b6. Although sperm PLC\u03b6 abrogation is extensively linked with human male infertility where oocyte activation is deficient, less is clear as to whether sperm PLC\u03b6 levels or localization underlies cases of defective embryogenesis and failed pregnancy following fertility treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>A cohort of 54 couples undergoing fertility treatment were recruited at the assisted reproductive technology laboratory at the King Faisal Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. The recruitment criteria for males was a minimum sperm concentration of 5\u00d7106 sperm\/ml, while all female patients had to have at least five oocytes. Sperm PLC\u03b6 analysis was performed in research laboratories, while semen assessments were performed, and time-lapse morphokinetic data were obtained, in the fertility clinic as part of routine treatment. The CRISPR\/Cas9 system was concurrently used to induce indels and single-nucleotide mutations within the Plc\u03b6 gene to generate strains of Plc\u03b6 mutant mice. Sperm PLC\u03b6 was evaluated using immunofluorescence and immunoblotting with an antibody of confirmed consistent specificity against PLC\u03b6.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>We evaluated PLC\u03b6 profiles in sperm samples from 54 human couples undergoing fertility treatment in the context of time-lapse morphokinetic analysis of resultant embryos, correlating such profiles to pregnancy status. Concurrently, we generated two strains of mutant Plc\u03b6 mice using CRISPR\/Cas9, and performed IVF with wild type (WT) oocytes and using WT or mutant Plc\u03b6 sperm to generate embryos. We also assessed PLC\u03b6 status in WT and mutant mice sperm in the context of time-lapse morphokinetic analysis and breeding outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>A significant (P\u2009\u2264\u20090.05) positive relationship was observed between both PLC\u03b6 relative fluorescence and relative density with the times taken for both the second cell division (CC2) (r\u2009=\u20090.26 and r\u2009=\u20090.43, respectively) and the third cell division (S2) (r\u2009=\u20090.26). Examination of localization patterns also indicated significant correlations between the presence or absence of sperm PLC\u03b6 and CC2 (r\u2009=\u20090.27 and r\u2009=\u2009\u22120.27, respectively; P\u2009\u2264\u20090.025). Human sperm PLC\u03b6 levels were at their highest in the ideal times of CC2 (8\u201312\u2009h) compared to time ranges outside the ideal timeframe (&amp;lt;8 and &amp;gt;12\u2009h) where levels of human sperm PLC\u03b6 were lower. Following assignment of PLC\u03b6 level thresholds, quantification revealed a significantly higher (P\u2009\u2264\u20090.05) rate of successful pregnancy in values larger than the assigned cut-off for both relative fluorescence (19% vs 40%, respectively) and relative density (8% vs 54%, respectively). Immunoblotting indicated a single band for PLC\u03b6 at 74\u2009kDa in sperm from WT mice, while a single band was also observed in sperm from heterozygous of Plc\u03b6 mutant mouse sperm, but at a diminished intensity. Immunofluorescent analysis indicated the previously reported (Kashir et al., 2021) fluorescence patterns in WT sperm, while sperm from Plc\u03b6 mutant mice exhibited a significantly diminished and dispersed pattern at the acrosomal region of the sperm head. Breeding experiments indicated a significantly reduced litter size of mutant Plc\u03b6 male mice compared to WT mice, while IVF-generated embryos using sperm from mutant Plc\u03b6 mice exhibited high rates of polyspermy, and resulted in significantly reduced numbers of these embryos reaching developmental milestones.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>The human population examined was relatively small, and should be expanded to examine a larger multi-centre cohort. Infertility conditions are often multivariable, and it was not possible to evaluate all these in human patients. However, our mutant Plc\u03b6 mouse experiments do suggest that PLC\u03b6 plays a significant role in early embryo development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>We found that minimal levels of PLC\u03b6 within a specific range were required for optimal early embryogenesis, correlating with increased pregnancy. Levels of sperm PLC\u03b6 below specific thresholds were associated with ineffective embryogenesis and lower pregnancy rates, despite eliciting successful fertilization in both mice and humans. To our knowledge, this represents the first time that PLC\u03b6 levels in sperm have been correlated to prognostic measures of embryogenic efficacy and pregnancy rates in humans. Our data suggest for the first time that the clinical utilization of PLC\u03b6 may stand to benefit not just a specific population of male infertility where oocyte activation is completely deficient (wherein PLC\u03b6 is completely defective\/abrogated), but also perhaps the larger population of couples seeking fertility treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>J.K. is supported by a faculty start up grant awarded by Khalifa University (FSU-2023-015). This study was also supported by a Healthcare Research Fellowship Award (HF-14-16) from Health and Care Research Wales (HCRW) to J.K., alongside a National Science, Technology, and Innovation plan (NSTIP) project grant (15-MED4186-20) awarded by the King Abdulaziz City for Science and Technology (KACST) for J.K. and A.M.A. The authors declare no conflicts of interest.<\/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\/deae078","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:46Z","timestamp":1714176046000},"page":"1256-1274","source":"Crossref","is-referenced-by-count":16,"title":["The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5056-8222","authenticated-orcid":false,"given":"Junaid","family":"Kashir","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, College of Medicine and Health Sciences, Khalifa University , Abu Dhabi, United Arab Emirates"},{"name":"Center for Biotechnology, Khalifa University , Abu Dhabi, United Arab Emirates"},{"name":"Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavesh V","family":"Mistry","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A","family":"Rajab","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujain","family":"BuSaleh","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raed","family":"Abu-Dawud","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"},{"name":"Institute for Molecular Medicine, MSH Medical School , Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala A","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Nomikos","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University , Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"AlHassan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7278-0902","authenticated-orcid":false,"given":"Serdar","family":"Coskun","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University , Riyadh, Saudi Arabia"},{"name":"Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M","family":"Assiri","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre , Riyadh, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University , Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"2024060305582052300_deae078-B1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3390\/ph16030441","article-title":"The therapeutic and diagnostic potential of phospholipase C zeta, oocyte activation, and calcium in treating human infertility","volume":"16","author":"Abdulsamad","year":"2023","journal-title":"Pharmaceuticals"},{"key":"2024060305582052300_deae078-B2","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/ncomms1424","article-title":"Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability","volume":"2","author":"Ajduk","year":"2011","journal-title":"Nat Commun"},{"key":"2024060305582052300_deae078-B3","doi-asserted-by":"crossref","first-page":"hoaa008","DOI":"10.1093\/hropen\/hoaa008","article-title":"Good practice recommendations for the use of time-lapse technology\u2020","volume":"2020","author":"Apter","year":"2020","journal-title":"Hum Reprod Open"},{"key":"2024060305582052300_deae078-B4","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/9780470773666.ch7","volume-title":"Statistical Methods in Medical Research","author":"Armitage","year":"2002"},{"key":"2024060305582052300_deae078-B5","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.aanat.2017.09.007","article-title":"Phospholipase C zeta parameters in sperm from polymorphic teratozoospermic men","volume":"215","author":"Azad","year":"2018","journal-title":"Ann Anat"},{"key":"2024060305582052300_deae078-B6","first-page":"178","article-title":"Oligoasthenoteratozoospermic (OAT) men display altered phospholipase C \u03b6 (PLC\u03b6) localization and a lower percentage of sperm cells expressing PLC\u03b6 and post-acrosomal sheath WW domain-binding protein (PAWP)","volume":"18","author":"Azad","year":"2017","journal-title":"Bosn J Basic Med Sci"},{"key":"2024060305582052300_deae078-B7","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1093\/humrep\/des210","article-title":"The impact of pronuclei morphology and dynamicity on live birth outcome after time-lapse culture","volume":"27","author":"Azzarello","year":"2012","journal-title":"Hum Reprod"},{"key":"2024060305582052300_deae078-B8","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.fertnstert.2016.11.014","article-title":"Examining the efficacy of six published time-lapse imaging embryo selection algorithms to predict implantation to demonstrate the need for the development of specific, in-house morphokinetic selection algorithms","volume":"107","author":"Barrie","year":"2017","journal-title":"Fertil Steril"},{"key":"2024060305582052300_deae078-B9","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/biomet\/93.3.491","article-title":"Adaptive linear step-up procedures that control the false discovery rate","volume":"93","author":"Benjamini","year":"2006","journal-title":"Biometrika"},{"key":"2024060305582052300_deae078-B10","volume-title":"An Introduction to Medical Statistics","author":"Bland","year":"2015","edition":"4th edn"},{"key":"2024060305582052300_deae078-B11","doi-asserted-by":"crossref","first-page":"W242","DOI":"10.1093\/nar\/gky354","article-title":"CRISPOR: intuitive guide selection for CRISPR\/Cas9 genome editing experiments and screens","volume":"46","author":"Concordet","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2024060305582052300_deae078-B12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/humrep\/dex344","article-title":"Focused time-lapse analysis reveals novel aspects of human fertilization and suggests new parameters of embryo viability","volume":"33","author":"Coticchio","year":"2018","journal-title":"Hum Reprod"},{"key":"2024060305582052300_deae078-B13","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1530\/rep.0.1240611","article-title":"Sperm phospholipase Czeta from humans and cynomolgus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes","volume":"124","author":"Cox","year":"2002","journal-title":"Reproduction"},{"key":"2024060305582052300_deae078-B14","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10815-011-9549-1","article-title":"Embryo quality, blastocyst and ongoing pregnancy rates in oocyte donation patients whose embryos were monitored by time-lapse imaging","volume":"28","author":"Cruz","year":"2011","journal-title":"J Assist Reprod Genet"},{"key":"2024060305582052300_deae078-B15","doi-asserted-by":"crossref","first-page":"a015834","DOI":"10.1101\/cshperspect.a015834","article-title":"Cytokinesis in animal cells","volume":"7","author":"D\u2019Avino","year":"2015","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2024060305582052300_deae078-B16","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1477-7827-12-54","article-title":"Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles","volume":"12","author":"Desai","year":"2014","journal-title":"Reprod Biol Endocrinol"},{"key":"2024060305582052300_deae078-B17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ydbio.2007.12.012","article-title":"The roles of Ca2+, downstream protein kinases, and oscillatory signaling in regulating fertilization and the activation of development","volume":"315","author":"Ducibella","year":"2008","journal-title":"Dev Biol"},{"key":"2024060305582052300_deae078-B18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1006\/dbio.2002.0788","article-title":"Egg-to-embryo transition is driven by differential responses to Ca2+ oscillation number","volume":"250","author":"Ducibella","year":"2002","journal-title":"Dev Biol"},{"key":"2024060305582052300_deae078-B19","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.semcdb.2006.02.010","article-title":"Role of calcium signals in early development","volume":"17","author":"Ducibella","year":"2006","journal-title":"Semin Cell Dev Biol"},{"key":"2024060305582052300_deae078-B20","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1093\/hmg\/ddv617","article-title":"Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP","volume":"25","author":"Escoffier","year":"2015","journal-title":"Hum Mol Genet"},{"key":"2024060305582052300_deae078-B21","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/molehr\/gau098","article-title":"Subcellular localization of phospholipase C\u03b6 in human sperm and its absence in DPY19L2-deficient sperm are consistent with its role in oocyte activation","volume":"21","author":"Escoffier","year":"2014","journal-title":"Mol Hum Reprod"},{"key":"2024060305582052300_deae078-B22","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s10815-016-0718-0","article-title":"PLC\u03b6 sequence, protein levels, and distribution in human sperm do not correlate with semen characteristics and fertilization rates after ICSI","volume":"33","author":"Ferrer-Vaquer","year":"2016","journal-title":"J Assist Reprod Genet"},{"key":"2024060305582052300_deae078-B23","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.ydbio.2004.07.025","article-title":"Mammalian phospholipase C\u03b6 induces oocyte activation from the sperm perinuclear matrix","volume":"274","author":"Fujimoto","year":"2004","journal-title":"Dev Biol"},{"key":"2024060305582052300_deae078-B24","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cub.2004.02.031","article-title":"First cleavage of the mouse embryo responds to change in egg shape at fertilization","volume":"14","author":"Gray","year":"2004","journal-title":"Curr Biol"},{"key":"2024060305582052300_deae078-B25","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 offspring can be conceived in its absence","volume":"144","author":"Hachem","year":"2017","journal-title":"Development"},{"key":"2024060305582052300_deae078-B26","first-page":"15.7.1","article-title":"Mouse genome editing using the CRISPR\/Cas system","volume":"83","author":"Harms","year":"2014","journal-title":"Curr Protoc Hum Genet"},{"key":"2024060305582052300_deae078-B27","doi-asserted-by":"crossref","first-page":"pdb.prot090704","DOI":"10.1101\/pdb.prot090704","article-title":"Generation of genetically modified mice using the CRISPR-Cas9 genome-editing system","volume":"2016","author":"Henao-Mejia","year":"2016","journal-title":"Cold Spring Harb Protoc"},{"key":"2024060305582052300_deae078-B28","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1093\/humrep\/dep207","article-title":"Reduced amounts and abnormal forms of phospholipase C zeta (PLC) in spermatozoa from infertile men","volume":"24","author":"Heytens","year":"2009","journal-title":"Hum Reprod"},{"key":"2024060305582052300_deae078-B29","doi-asserted-by":"crossref","first-page":"980","DOI":"10.3390\/life13040980","article-title":"Successful production of offspring derived from phospholipase C zeta-deficient sperm by additional artificial activation","volume":"13","author":"Hirose","year":"2023","journal-title":"Life"},{"key":"2024060305582052300_deae078-B30","doi-asserted-by":"crossref","first-page":"513","DOI":"10.33549\/physiolres.932287","article-title":"Time-lapse cleavage rating predicts human embryo viability","volume":"61","author":"Hlinka","year":"2012","journal-title":"Physiol Res"},{"key":"2024060305582052300_deae078-B31","doi-asserted-by":"crossref","first-page":"F53","DOI":"10.1530\/REP-21-0458","article-title":"Sperm factors and egg activation: phospholipase C zeta (PLCZ1) and the clinical diagnosis of oocyte activation deficiency","volume":"164","author":"Jones","year":"2022","journal-title":"Reproduction"},{"key":"2024060305582052300_deae078-B32","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/molehr\/gay038","article-title":"Mammalian sperm contain two factors for calcium release and egg activation: phospholipase C zeta and a cryptic activating factor","volume":"24","author":"Jones","year":"2018","journal-title":"Mol Hum Reprod"},{"key":"2024060305582052300_deae078-B33","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":"2024060305582052300_deae078-B34","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/molehr\/gaw073","article-title":"Antigen unmasking enhances visualization efficacy of the oocyte activation factor, phospholipase C zeta, in mammalian sperm","volume":"23","author":"Kashir","year":"2016","journal-title":"Mol Hum Reprod"},{"key":"2024060305582052300_deae078-B35","doi-asserted-by":"crossref","first-page":"hoac003","DOI":"10.1093\/hropen\/hoac003","article-title":"Oocyte activation deficiency and assisted oocyte activation: mechanisms, obstacles and prospects for clinical application","volume":"2022","author":"Kashir","year":"2022","journal-title":"Hum Reprod Open"},{"key":"2024060305582052300_deae078-B36","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":"2024060305582052300_deae078-B37","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1095\/biolreprod.112.103853","article-title":"Viability assessment for artificial gametes: the need for biomarkers of functional competency1","volume":"87","author":"Kashir","year":"2012","journal-title":"Biol Reprod"},{"key":"2024060305582052300_deae078-B38","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/978-94-007-2888-2_50","article-title":"Calcium oscillations, oocyte activation, and phospholipase C zeta","volume":"740","author":"Kashir","year":"2012","journal-title":"Adv Exp Med Biol"},{"key":"2024060305582052300_deae078-B39","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1093\/humrep\/der336","article-title":"Loss of activity mutations in phospholipase C zeta (PLC) abolishes calcium oscillatory ability of human recombinant protein in mouse oocytes","volume":"26","author":"Kashir","year":"2011","journal-title":"Hum Reprod"},{"key":"2024060305582052300_deae078-B40","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.fertnstert.2012.09.001","article-title":"Variance in total levels of phospholipase C zeta (PLC-\u03b6) in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of oocyte activation capability","volume":"99","author":"Kashir","year":"2013","journal-title":"Fertil Steril"},{"key":"2024060305582052300_deae078-B41","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.fertnstert.2012.05.002","article-title":"Characterization of two heterozygous mutations of the oocyte activation factor phospholipase C zeta (PLC\u03b6) from an infertile man by use of minisequencing of individual sperm and expression in somatic cells","volume":"98","author":"Kashir","year":"2012","journal-title":"Fertil Steril"},{"key":"2024060305582052300_deae078-B42","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1093\/humrep\/der384","article-title":"A maternally inherited autosomal point mutation in human phospholipase C zeta (PLC) leads to male infertility","volume":"27","author":"Kashir","year":"2011","journal-title":"Hum Reprod"},{"key":"2024060305582052300_deae078-B43","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1111\/andr.12796","article-title":"Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment","volume":"8","author":"Kashir","year":"2020","journal-title":"Andrology"},{"key":"2024060305582052300_deae078-B44","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3390\/ph16020198","article-title":"Antigen unmasking is required to clinically assess levels and localisation patterns of phospholipase C zeta in human sperm","volume":"16","author":"Kashir","year":"2023","journal-title":"Pharmaceuticals"},{"key":"2024060305582052300_deae078-B45","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":"2024060305582052300_deae078-B46","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jbior.2017.10.012","article-title":"Phospholipase C zeta and calcium oscillations at fertilisation: the evidence, applications, and further questions","volume":"67","author":"Kashir","year":"2018","journal-title":"Adv Biol Regul"},{"key":"2024060305582052300_deae078-B2416380","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/molehr\/gav009","article-title":"PLC\u03b6 or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis","volume":"21","author":"Kashir","year":"2015","journal-title":"Mol Hum Reprod"},{"key":"2024060305582052300_deae078-B47","doi-asserted-by":"crossref","first-page":"90","DOI":"10.5653\/cerm.2017.44.2.90","article-title":"Evaluation of human embryo development in in vitro fertilization- and intracytoplasmic sperm injection-fertilized oocytes: a time-lapse study","volume":"44","author":"Kim","year":"2017","journal-title":"Clin Exp Reprod Med"},{"key":"2024060305582052300_deae078-B48","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/1477-7827-9-123","article-title":"The IMSI procedure improves poor embryo development in the same infertile couples with poor semen quality: a comparative prospective randomized study","volume":"9","author":"Knez","year":"2011","journal-title":"Reprod Biol Endocrinol"},{"key":"2024060305582052300_deae078-B49","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1095\/biolreprod.104.036244","article-title":"Transgenic RNA interference reveals role for mouse sperm phospholipase C\u03b6 in triggering Ca2+ oscillations during fertilization1","volume":"72","author":"Knott","year":"2005","journal-title":"Biol Reprod"},{"key":"2024060305582052300_deae078-B50","doi-asserted-by":"crossref","first-page":"10408","DOI":"10.1074\/jbc.M313801200","article-title":"Recombinant phospholipase C\u03b6 has high Ca2+ sensitivity and induces Ca2+ oscillations in mouse eggs","volume":"279","author":"Kouchi","year":"2004","journal-title":"J Biol Chem"},{"key":"2024060305582052300_deae078-B51","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/1477-7827-12-124","article-title":"Embryo selection: the role of time-lapse monitoring","volume":"12","author":"Kovacs","year":"2014","journal-title":"Reprod Biol Endocrinol"},{"key":"2024060305582052300_deae078-B52","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ydbio.2005.06.029","article-title":"Functional, biochemical, and chromatographic characterization of the complete [Ca2+]i oscillation-inducing activity of porcine sperm","volume":"285","author":"Kurokawa","year":"2005","journal-title":"Dev Biol"},{"key":"2024060305582052300_deae078-B53","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10815-006-9022-8","article-title":"The effects of sperm quality on embryo development after intracytoplasmic sperm injection","volume":"23","author":"Loutradi","year":"2006","journal-title":"J Assist Reprod Genet"},{"key":"2024060305582052300_deae078-B54","volume-title":"Embryo Cleavage","author":"Meng Ju","year":"2017"},{"key":"2024060305582052300_deae078-B55","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1093\/humrep\/der256","article-title":"The use of morphokinetics as a predictor of embryo implantation","volume":"26","author":"Meseguer","year":"2011","journal-title":"Hum Reprod"},{"key":"2024060305582052300_deae078-B56","doi-asserted-by":"crossref","first-page":"R37","DOI":"10.1530\/REP-17-0004","article-title":"Time-lapse imaging of cleavage divisions in embryo quality assessment","volume":"154","author":"Milewski","year":"2017","journal-title":"Reproduction"},{"key":"2024060305582052300_deae078-B57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/REP-17-0230","article-title":"Dynamics of cytoplasm and cleavage divisions correlates with preimplantation embryo development","volume":"155","author":"Milewski","year":"2018","journal-title":"Reproduction"},{"key":"2024060305582052300_deae078-B58","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1254\/jphs.CPJ06003X","article-title":"Calcium signals for egg activation in mammals","volume":"100","author":"Miyazaki","year":"2006","journal-title":"J Pharmacol Sci"},{"key":"2024060305582052300_deae078-B59","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.fertnstert.2014.05.004","article-title":"Sperm involved in recurrent partial hydatidiform moles cannot induce the normal pattern of calcium oscillations","volume":"102","author":"Nikiforaki","year":"2014","journal-title":"Fertil Steril"},{"key":"2024060305582052300_deae078-B60","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1093\/molehr\/gav034","article-title":"PLC\u03b6 or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis","volume":"21","author":"Nomikos","year":"2015","journal-title":"Mol Hum Reprod"},{"key":"2024060305582052300_deae078-B61","doi-asserted-by":"crossref","first-page":"29519","DOI":"10.1074\/jbc.M115.658443","article-title":"Essential role of the EF-hand domain in targeting sperm phospholipase C\u03b6 to membrane phosphatidylinositol 4,5-bisphosphate (PIP2)","volume":"290","author":"Nomikos","year":"2015","journal-title":"J Biol Chem"},{"key":"2024060305582052300_deae078-B62","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1042\/BCJ20161057","article-title":"Male infertility-linked point mutation reveals a vital binding role for the C2 domain of sperm PLC\u03b6","volume":"474","author":"Nomikos","year":"2017","journal-title":"Biochem J"},{"key":"2024060305582052300_deae078-B63","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1016\/j.febslet.2014.07.007","article-title":"Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death","volume":"588","author":"Nomikos","year":"2014","journal-title":"FEBS Lett"},{"key":"2024060305582052300_deae078-B64","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/molehr\/gau011","article-title":"Human PLC exhibits superior fertilization potency over mouse PLC in triggering the Ca2+ oscillations required for mammalian oocyte activation","volume":"20","author":"Nomikos","year":"2014","journal-title":"Mol Hum Reprod"},{"key":"2024060305582052300_deae078-B65","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.fertnstert.2012.08.035","article-title":"Phospholipase C\u03b6 rescues failed oocyte activation in a prototype of male factor infertility","volume":"99","author":"Nomikos","year":"2013","journal-title":"Fertil Steril"},{"key":"2024060305582052300_deae078-B66","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/s41598-018-19497-6","article-title":"Sperm-borne phospholipase C zeta-1 ensures monospermic fertilization in mice","volume":"8","author":"Nozawa","year":"2018","journal-title":"Sci Rep"},{"key":"2024060305582052300_deae078-B67","doi-asserted-by":"crossref","first-page":"232","DOI":"10.5468\/ogs.2015.58.3.232","article-title":"Relationship between phospholipase C zeta immunoreactivity and DNA fragmentation and oxidation in human sperm","volume":"58","author":"Park","year":"2015","journal-title":"Obstet Gynecol Sci"},{"key":"2024060305582052300_deae078-B68","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-1-4939-8831-0_2","volume-title":"Microinjection: Methods and Protocols","author":"Pu","year":"2019"},{"key":"2024060305582052300_deae078-B69","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1007\/s10815-019-01567-x","article-title":"Performance of day 5 KIDScore\u2122 morphokinetic prediction models of implantation and live birth after single blastocyst transfer","volume":"36","author":"Reignier","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"2024060305582052300_deae078-B70","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1242\/dev.129.15.3533","article-title":"PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development","volume":"129","author":"Saunders","year":"2002","journal-title":"Development"},{"key":"2024060305582052300_deae078-B71","doi-asserted-by":"crossref","first-page":"e0242377","DOI":"10.1371\/journal.pone.0242377","article-title":"Time-lapse imaging derived morphokinetic variables reveal association with implantation and live birth following in vitro fertilization: a retrospective study using data from transferred human embryos","volume":"15","author":"Sayed","year":"2020","journal-title":"PLoS One"},{"key":"2024060305582052300_deae078-B72","doi-asserted-by":"crossref","first-page":"V9","DOI":"10.1530\/REP-20-0079","article-title":"The soluble sperm factor that activates the egg: PLCzeta and beyond","volume":"160","author":"Swann","year":"2020","journal-title":"Reproduction"},{"key":"2024060305582052300_deae078-B73","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0074-7696(08)62557-7","article-title":"Dynamics of the calcium signal that triggers mammalian egg activation","volume":"152","author":"Swann","year":"1994","journal-title":"Int Rev Cytol"},{"key":"2024060305582052300_deae078-B74","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.rbmo.2022.03.019","article-title":"Time-lapse KIDScoreD5 for prediction of embryo pregnancy potential in fresh and vitrified-warmed single-embryo transfers","volume":"45","author":"Tartia","year":"2022","journal-title":"Reprod Biomed Online"},{"key":"2024060305582052300_deae078-B75","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1080\/19396368.2017.1298006","article-title":"Relationship between phospholipase C-zeta, semen parameters, and chromatin status","volume":"63","author":"Tavalaee","year":"2017","journal-title":"Syst Biol Reprod Med"},{"key":"2024060305582052300_deae078-B76","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.rbmo.2017.12.013","article-title":"Expression of sperm PLC\u03b6 and clinical outcomes of ICSI-AOA in men affected by globozoospermia due to DPY19L2 deletion","volume":"36","author":"Tavalaee","year":"2018","journal-title":"Reprod Biomed Online"},{"key":"2024060305582052300_deae078-B77","first-page":"104","volume-title":"Time-Lapse Microscopy In In-Vitro Fertilization","author":"Tejera","year":"2016"},{"key":"2024060305582052300_deae078-B78","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1093\/humrep\/dez094","article-title":"Novel phospholipase C zeta 1 mutations associated with fertilization failures after ICSI","volume":"34","author":"Torra-Massana","year":"2019","journal-title":"Hum Reprod"},{"key":"2024060305582052300_deae078-B79","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/humupd\/dmad006","article-title":"Contribution of semen to early embryo development: fertilization and beyond","volume":"29","author":"Vallet-Buisan","year":"2023","journal-title":"Hum Reprod Update"},{"key":"2024060305582052300_deae078-B80","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/j.bbagen.2015.07.001","article-title":"Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease","volume":"1850","author":"Vassilakopoulou","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"2024060305582052300_deae078-B81","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3390\/ijms24010314","article-title":"PLCZ1 deficiency decreased fertility in male mice which is associated with sperm quality decline and abnormal cytoskeleton in epididymis","volume":"24","author":"Wang","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2024060305582052300_deae078-B82","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen","author":"WHO","year":"2010","edition":"5th edn"},{"key":"2024060305582052300_deae078-B83","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/nbt.1686","article-title":"Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage","volume":"28","author":"Wong","year":"2010","journal-title":"Nat Biotechnol"},{"key":"2024060305582052300_deae078-B84","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ceca.2017.03.002","article-title":"The establishment of appropriate methods for egg-activation by human PLCZ1 RNA injection into human oocyte","volume":"65","author":"Yamaguchi","year":"2017","journal-title":"Cell Calcium"},{"key":"2024060305582052300_deae078-B85","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1038\/nprot.2014.134","article-title":"Generating genetically modified mice using CRISPR\/Cas-mediated genome engineering","volume":"9","author":"Yang","year":"2014","journal-title":"Nat Protoc"},{"key":"2024060305582052300_deae078-B86","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.rbmo.2015.02.008","article-title":"Cleavage pattern predicts developmental potential of day 3 human embryos produced by IVF","volume":"30","author":"Yang","year":"2015","journal-title":"Reprod Biomed Online"},{"key":"2024060305582052300_deae078-B87","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.fertnstert.2015.05.018","article-title":"Total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta are significantly correlated with fertilization rates after intracytoplasmic sperm injection","volume":"104","author":"Yelumalai","year":"2015","journal-title":"Fertil Steril"},{"key":"2024060305582052300_deae078-B88","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1093\/humrep\/des092","article-title":"Recombinant human phospholipase C zeta 1 induces intracellular calcium oscillations and oocyte activation in mouse and human oocytes","volume":"27","author":"Yoon","year":"2012","journal-title":"Hum Reprod"},{"key":"2024060305582052300_deae078-B89","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1172\/JCI36942","article-title":"Human sperm devoid of PLC, zeta 1 fail to induce Ca2+ release and are unable to initiate the first step of embryo development","volume":"118","author":"Yoon","year":"2008","journal-title":"J Clin Invest"},{"key":"2024060305582052300_deae078-B90","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1091\/mbc.e11-08-0687","article-title":"PLC\u03b6 causes Ca(2+) oscillations in mouse eggs by targeting intracellular and not plasma membrane PI(4,5)P(2)","volume":"23","author":"Yu","year":"2012","journal-title":"Mol Biol Cell"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/39\/6\/1256\/58039810\/deae078.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/39\/6\/1256\/58039810\/deae078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T14:48:40Z","timestamp":1717426120000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/39\/6\/1256\/7658906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,26]]},"references-count":91,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,4,26]]},"published-print":{"date-parts":[[2024,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deae078","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,6,1]]},"published":{"date-parts":[[2024,4,26]]}}}