{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:32:25Z","timestamp":1786739545887,"version":"build-2736575974"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Sperm-specific phospholipase C zeta (PLC\u03b6) initiates intracellular calcium (Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ) transients which drive a series of concurrent events collectively termed oocyte activation. Numerous investigations have linked abrogation and absence\/reduction of PLC\u03b6 with forms of male infertility in humans where oocyte activation fails. However, very few studies have examined potential relationships between PLC\u03b6 and advancing male age, both of which are increasingly considered to be major effectors of male fertility. Initial efforts in humans may be hindered by inherent PLC\u03b6 variability within the human population, alongside a lack of sufficient controllable repeats. Herein, utilizing immunoblotting, immunofluorescence, and quantitative reverse transcription PCR (qRT-PCR) we examined for the first time PLC\u03b6 protein levels and localization patterns in sperm, and PLC\u03b6 mRNA levels within testes, from mice at 8 weeks, 12 weeks, 24 weeks, and 36 weeks of age, from two separate strains of mice, C57BL\/6 (B6; inbred) and CD1 (outbred). Collectively, advancing male age generally diminished levels and variability of PLC\u03b6 protein and mRNA in sperm and testes, respectively, when both strains were examined. Furthermore, advancing male age altered the predominant pattern of PLC\u03b6 localization in mouse sperm, with younger mice exhibiting predominantly post-acrosomal, and older mice exhibiting both post-acrosomal and acrosomal populations of PLC\u03b6. However, the specific pattern of such decline in levels of protein and mRNA was strain-specific. Collectively, our results demonstrate a negative relationship between advancing male age and PLC\u03b6 levels and localization patterns, indicating that aging male mice from different strains may serve as useful models to investigate PLC\u03b6 in cases of male infertility and subfertility in humans.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/aja.aja_67_20","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T09:59:05Z","timestamp":1605607145000},"page":"178-187","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":11,"title":["Advancing male age differentially alters levels and localization patterns of PLCzeta in sperm and testes from different mouse strains"],"prefix":"10.4103","volume":"23","author":[{"given":"Junaid","family":"Kashir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavesh V","family":"Mistry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha Adel","family":"Gumssani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Rajab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reema","family":"Abu-Dawas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falah","family":"AlMohanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Nomikos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raed","family":"Abu-Dawud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadya","family":"Al-Yacoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Coward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F Anthony","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M","family":"Assiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-10-20240829","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1530\/rep.0.1240611","article-title":"Sperm phospholipase C zeta from humans and cynomolgus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes","volume":"124","author":"Cox","year":"2002","journal-title":"Reproduction"},{"key":"R2-10-20240829","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1242\/dev.129.15.3533","article-title":"PLC zeta: a sperm-specific trigger of Ca2+ oscillations in eggs and embryo development","volume":"129","author":"Saunders","year":"2002","journal-title":"Development"},{"key":"R3-10-20240829","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.ydbio.2004.07.025","article-title":"Mammalian phospholipase Czeta induces oocyte activation from the sperm perinuclear matrix","volume":"274","author":"Fujimoto","year":"2004","journal-title":"Dev Biol"},{"key":"R4-10-20240829","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":"R5-10-20240829","doi-asserted-by":"crossref","first-page":"10408","DOI":"10.1074\/jbc.M313801200","article-title":"Recombinant phospholipase Czeta has high Ca2+ sensitivity and induces Ca2+ oscillations in mouse eggs","volume":"279","author":"Kouchi","year":"2004","journal-title":"J Biol Chem"},{"key":"R6-10-20240829","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1095\/biolreprod.104.036244","article-title":"Transgenic RNA interference reveals role for mouse sperm phospholipase Czeta in triggering Ca2+ oscillations during fertilization","volume":"72","author":"Knott","year":"2005","journal-title":"Biol Reprod"},{"key":"R7-10-20240829","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":"14","author":"Hachem","year":"2017","journal-title":"Development"},{"key":"R8-10-20240829","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":"R9-10-20240829","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":"R10-10-20240829","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"},{"key":"R11-10-20240829","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":"R12-10-20240829","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":"R13-10-20240829","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 fertilization success in patients undergoing fertility treatment","volume":"8","author":"Kashir","year":"2020","journal-title":"Andrology"},{"key":"R14-10-20240829","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fendo.2019.00035","article-title":"Impact of paternal age on seminal parameters and reproductive outcome of intracytoplasmatic sperm injection in infertile Italian women","volume":"10","author":"Gallo","year":"2019","journal-title":"Front Endocrinol (Lausanne"},{"key":"R15-10-20240829","doi-asserted-by":"crossref","first-page":"27543","DOI":"10.1038\/srep27543","article-title":"Does advancing male age influence the expression levels and localization patterns of phospholipase C zeta (PLC\u03b6) in human sperm?","volume":"6","author":"Yeste","year":"2016","journal-title":"Sci Rep"},{"key":"R16-10-20240829","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-zeta) 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":"R17-10-20240829","doi-asserted-by":"crossref","first-page":"19357","DOI":"10.1038\/srep19357","article-title":"Ca2+ dynamics in oocytes from naturally-aged mice","volume":"6","author":"Haverfield","year":"2016","journal-title":"Sci Rep"},{"key":"R18-10-20240829","first-page":"3483","article-title":"Inbreeding depresses sperm competitiveness, but not fertilization or mating success in male Tribolium castaneum","volume":"277","author":"Michalczyk","year":"2010","journal-title":"Proc Biol Sci"},{"key":"R19-10-20240829","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1530\/REP-13-0425","article-title":"High-fertility phenotypes: two outbred mouse models exhibit substantially different molecular and physiological strategies warranting improved fertility","volume":"147","author":"Langhammer","year":"2014","journal-title":"Reproduction"},{"key":"R20-10-20240829","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":"2017","journal-title":"Mol Hum Reprod"},{"key":"R21-10-20240829","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":"R22-10-20240829","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"R23-10-20240829","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":"R24-10-20240829","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 PLCzeta","volume":"474","author":"Nomikos","year":"2017","journal-title":"Biochem J"},{"key":"R25-10-20240829","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.arr.2014.10.007","article-title":"Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis","volume":"19","author":"Johnson","year":"2015","journal-title":"Ageing Res Rev"},{"key":"R26-10-20240829","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1016\/j.celrep.2019.08.043","article-title":"Age-related gene expression signature in rats demonstrate early, late, and linear transcriptional changes from multiple tissues","volume":"28","author":"Shavlakadze","year":"2019","journal-title":"Cell Rep"},{"key":"R27-10-20240829","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/bies.201100157","article-title":"Are old males still good males and can females tell the difference. bDo hidden advantages of mating with old males off-set costs related to fertility, or are we missing something else?","volume":"34","author":"Johnson","year":"2012","journal-title":"Bioessays"},{"key":"R28-10-20240829","first-page":"20172174","article-title":"Evidence that fertility trades off with early offspring fitness as males age","volume":"285","author":"Johnson","year":"2018","journal-title":"Proc Biol Sci"},{"key":"R29-10-20240829","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1016\/j.fertnstert.2008.05.021","article-title":"Phospholipase C zeta undergoes dynamic changes in its pattern of localization in sperm during capacitation and the acrosome reaction","volume":"91","author":"Young","year":"2009","journal-title":"Fertil Steril"},{"key":"R30-10-20240829","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"},{"key":"R31-10-20240829","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/aja.2009.6","article-title":"NYD-SP27, a novel intrinsic decapacitation factor in sperm","volume":"11","author":"Bi","year":"2009","journal-title":"Asian J Androl"},{"key":"R32-10-20240829","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.rbmo.2009.12.024","article-title":"Complete globozoospermia associated with PLC\u03b6 deficiency treated with calcium ionophore and ICSI results in pregnancy","volume":"20","author":"Taylor","year":"2010","journal-title":"Reprod Biomed Online"},{"key":"R33-10-20240829","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1093\/humrep\/der258","article-title":"Successful childbirth after intracytoplasmic morphologically selected sperm injection without assisted oocyte activation in a patient with globozoospermia","volume":"26","author":"Sermondade","year":"2011","journal-title":"Hum Reprod"},{"key":"R34-10-20240829","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1093\/humrep\/des312","article-title":"Motile sperm organelle morphology evaluation-selected globozoospermic human sperm with an acrosomal bud exhibits novel patterns and higher levels of phospholipase C zeta","volume":"27","author":"Kashir","year":"2012","journal-title":"Hum Reprod"},{"key":"R35-10-20240829","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 C zeta","volume":"132","author":"Yoneda","year":"2006","journal-title":"Reproduction"},{"key":"R36-10-20240829","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/mrd.21097","article-title":"Phospholipase C\u03b6 mRNA expression and its potency during spermatogenesis for activation of quail oocyte as a sperm factor","volume":"76","author":"Mizushima","year":"2009","journal-title":"Mol Reprod Dev"},{"key":"R37-10-20240829","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":"R38-10-20240829","doi-asserted-by":"crossref","first-page":"e33496","DOI":"10.1371\/journal.pone.0033496","article-title":"The testicular and epididymal expression profile of PLC\u03b6 in mouse and human does not support its role as a sperm-borne oocyte activating factor","volume":"7","author":"Aarabi","year":"2012","journal-title":"PLoS One"},{"key":"R40-10-20240829","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":"R41-10-20240829","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/s41592-018-0224-7","article-title":"Comparing phenotypic variation between inbred and outbred mice","volume":"15","author":"Tuttle","year":"2018","journal-title":"Nat Methods"},{"key":"R42-10-20240829","first-page":"217","article-title":"Exotic mice as models for aging research: polemic and prospectus","volume":"20","author":"Miller","year":"1999","journal-title":"Neurobiol Aging"},{"key":"R43-10-20240829","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"},{"key":"R44-10-20240829","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1093\/humrep\/der200","article-title":"A sperm's tail: the importance of getting it right","volume":"26","author":"Ramalho-Santos","year":"2011","journal-title":"Hum Reprod"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja.aja_67_20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:29:53Z","timestamp":1786735793000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja.aja_67_20"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.4103\/aja.aja_67_20","relation":{},"ISSN":["1008-682X"],"issn-type":[{"value":"1008-682X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]}}}