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PLCZeta
Sponsor study identifier
Secondary identifiers
OTHER · Department of Health Abu Dhabi
observational
200
1 country
2
Study Start
July 1, 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
Primary Completion
July 1, 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
Study Completion
August 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
With declining fertility rates Worldwide, Assisted Reproductive Technology is seen as a viable solution for infertility, however, individual success rates following ART remain relatively low, rarely exceeding \~50%. The European Society for Human Reproduction and Embryology (ESHRE) indicates pregnancy rates per embryo transfer remain below 50%. Additionally, male infertility is regarded as a leading contributor to global infertility with approximately a third of cases attributed to genetic causes while half of the cases remain unexplained. In this observational study we investigate the correlation between phospholipase C Zeta (PLCζ ) measurements and semen parameters. PLCζ is a sperm-specific protein which is introduced into a mature egg (oocyte) following gamete fusion and upon introduction, PLCζ is believed to initiate a series of characteristic calcium ion oscillations which lead to oocyte activation and persist beyond the completion of meiosis. Mounting evidence implicates defects in PLCζ in cases of male factor infertility where intracytoplasmic sperm injection (ICSI; whereby a single sperm is injected into the oocyte) is unsuccessful. Furthermore, defects in PLCζ are also increasingly implicated in cases of male sub-fertility, which affects a much larger proportion of the global population. Numerous studies now indicate that PLCζ not only holds significant value as a therapeutic to rescue cases of ICSI failure, but also as a prognostic diagnostic test of male fertility. Indeed, the reduction or absence of normal PLCζ within sperm has been linked to cases of male factor infertility in humans, either due to inactivation through mutation, due to abrogation of protein levels in sperm as a result of mutation in the PLCζ promoter, or mutations within coding exonic regions of the PLCζ gene. Such data indicate both therapeutic, and diagnostic applications for PLCζ within the fertility clinic. This study seeks to determine the effect of abnormal PLCζ on semen parameters and correlate that with downstream events including clinical pregnancy and live birth rates.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
August 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
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Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
June 29, 2026
Actual (reported)July 1, 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
July 6, 2026
Actual (reported)July 1, 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
August 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
Biochemical pregnancy
Blood tested positive/ negative for pregnancy
From enrollment to clinical pregnancy result and delivery where applicable.
Clinical Pregnancy result
Confirmation of presence or absence of a gestational sac and fetal heartbeat using ultrasound detection.
From enrollment to delivery (live birth or miscarriage)
PLC Zeta measurement
Measurement of PLC Zeta by Immunofluorescence and Western Blotting
From enrollment to submission of sperm (1 day)
Live birth or miscarriage
From enrollment to delivery or miscarriage.
Male partners in couples seeking fertility treatment via IVF and excluding any couples with factors known to negatively affect in spermatogenesis and embryogenesis. Couples must be experiencing infertility for 1 year or more before beginning IVF treatment.
This is a cohort observational study and there will be no intervention of any type.
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Male partners in couples suffering from infertility and seeking IVF treatment at the FAKIH IVF clinics in the UAE.
Fakih IVF
Abu Dhabi, United Arab Emirates
Khalifa University
World Health Organization, 2010, Fifth Edition. ISBN: 978 92 4 154778 9.
Yamaguchi et al., Cell Calcium 2017;pii: S0143-4160(16)30191-9.
Janghorban-Laricheh E, Ghazavi-Khorasgani N, Tavalaee M, Zohrabi D, Abbasi H, Nasr-Esfahani MH. An association between sperm PLCzeta levels and varicocele? J Assist Reprod Genet. 2016 Dec;33(12):1649-1655. doi: 10.1007/s10815-016-0802-5. Epub 2016 Sep 9.
Junaid Kashir, PhD
Khalifa University
Dr. Lamiya Mohiyiddeen, MD
Fakih IVF Abu Dhabi
Michael Fakih, MD
Fakih IVF Abu Dhabi
First Submitted
June 29, 2026
First Posted
July 6, 2026
Study Start
July 1, 2026
Estimated (date passed)This estimate has passed. The registry has not confirmed an actual date for this milestone.
Primary Completion
July 1, 2027
Contact the study team to confirm eligibility.
Abu Dhabi, United Arab Emirates
Kamali-Dolat Abadi M, Tavalaee M, Shahverdi A, Nasr-Esfahani MH. Evaluation of PLCzeta and PAWP Expression in Globozoospermic Individuals. Cell J. 2016 Fall;18(3):438-45. doi: 10.22074/cellj.2016.4572. Epub 2016 Aug 24.
Wong CC, Loewke KE, Bossert NL, Behr B, De Jonge CJ, Baer TM, Reijo Pera RA. Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat Biotechnol. 2010 Oct;28(10):1115-21. doi: 10.1038/nbt.1686. Epub 2010 Oct 3.
Miyazaki S, Ito M. Calcium signals for egg activation in mammals. J Pharmacol Sci. 2006;100(5):545-52. doi: 10.1254/jphs.cpj06003x.
Fulton BP, Whittingham DG. Activation of mammalian oocytes by intracellular injection of calcium. Nature. 1978 May 11;273(5658):149-51. doi: 10.1038/273149a0. No abstract available.
Ducibella T, Schultz RM, Ozil JP. Role of calcium signals in early development. Semin Cell Dev Biol. 2006 Apr;17(2):324-32. doi: 10.1016/j.semcdb.2006.02.010. Epub 2006 Mar 2.
Ducibella T, Huneau D, Angelichio E, Xu Z, Schultz RM, Kopf GS, Fissore R, Madoux S, Ozil JP. Egg-to-embryo transition is driven by differential responses to Ca(2+) oscillation number. Dev Biol. 2002 Oct 15;250(2):280-91.
Escoffier J, Lee HC, Yassine S, Zouari R, Martinez G, Karaouzene T, Coutton C, Kherraf ZE, Halouani L, Triki C, Nef S, Thierry-Mieg N, Savinov SN, Fissore R, Ray PF, Arnoult C. Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP. Hum Mol Genet. 2016 Mar 1;25(5):878-91. doi: 10.1093/hmg/ddv617. Epub 2015 Dec 31.
Ferrer-Vaquer A, Barragan M, Freour T, Vernaeve V, Vassena R. PLCzeta sequence, protein levels, and distribution in human sperm do not correlate with semen characteristics and fertilization rates after ICSI. J Assist Reprod Genet. 2016 Jun;33(6):747-56. doi: 10.1007/s10815-016-0718-0. Epub 2016 May 2.
Kashir J, Konstantinidis M, Jones C, Heindryckx B, De Sutter P, Parrington J, Wells D, Coward K. Characterization of two heterozygous mutations of the oocyte activation factor phospholipase C zeta (PLCzeta) from an infertile man by use of minisequencing of individual sperm and expression in somatic cells. Fertil Steril. 2012 Aug;98(2):423-31. doi: 10.1016/j.fertnstert.2012.05.002. Epub 2012 May 24.
Kashir J, Konstantinidis M, Jones C, Lemmon B, Lee HC, Hamer R, Heindryckx B, Deane CM, De Sutter P, Fissore RA, Parrington J, Wells D, Coward K. A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCzeta) leads to male infertility. Hum Reprod. 2012 Jan;27(1):222-31. doi: 10.1093/humrep/der384. Epub 2011 Nov 16.
Kashir J, Buntwal L, Nomikos M, Calver BL, Stamatiadis P, Ashley P, Vassilakopoulou V, Sanders D, Knaggs P, Livaniou E, Bunkheila A, Swann K, Lai FA. Antigen unmasking enhances visualization efficacy of the oocyte activation factor, phospholipase C zeta, in mammalian sperm. Mol Hum Reprod. 2017 Jan;23(1):54-67. doi: 10.1093/molehr/gaw073. Epub 2016 Dec 8.
Theodoridou M, Nomikos M, Parthimos D, Gonzalez-Garcia JR, Elgmati K, Calver BL, Sideratou Z, Nounesis G, Swann K, Lai FA. Chimeras of sperm PLCzeta reveal disparate protein domain functions in the generation of intracellular Ca2+ oscillations in mammalian eggs at fertilization. Mol Hum Reprod. 2013 Dec;19(12):852-64. doi: 10.1093/molehr/gat070. Epub 2013 Oct 23.
Kashir J, Nomikos M, Lai FA, Swann K. Sperm-induced Ca2+ release during egg activation in mammals. Biochem Biophys Res Commun. 2014 Aug 1;450(3):1204-11. doi: 10.1016/j.bbrc.2014.04.078. Epub 2014 Apr 21.
Kashir J, Heynen A, Jones C, Durrans C, Craig J, Gadea J, Turner K, Parrington J, Coward K. Effects of cryopreservation and density-gradient washing on phospholipase C zeta concentrations in human spermatozoa. Reprod Biomed Online. 2011 Aug;23(2):263-7. doi: 10.1016/j.rbmo.2011.04.006. Epub 2011 May 7.
Kashir J, Jones C, Lee HC, Rietdorf K, Nikiforaki D, Durrans C, Ruas M, Tee ST, Heindryckx B, Galione A, De Sutter P, Fissore RA, Parrington J, Coward K. Loss of activity mutations in phospholipase C zeta (PLCzeta) abolishes calcium oscillatory ability of human recombinant protein in mouse oocytes. Hum Reprod. 2011 Dec;26(12):3372-87. doi: 10.1093/humrep/der336. Epub 2011 Oct 18.
Yoon SY, Jellerette T, Salicioni AM, Lee HC, Yoo MS, Coward K, Parrington J, Grow D, Cibelli JB, Visconti PE, Mager J, Fissore RA. Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development. J Clin Invest. 2008 Nov;118(11):3671-81. doi: 10.1172/JCI36942. Epub 2008 Oct 16.
Saunders CM, Larman MG, Parrington J, Cox LJ, Royse J, Blayney LM, Swann K, Lai FA. PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development. Development. 2002 Aug;129(15):3533-44. doi: 10.1242/dev.129.15.3533.
Ito J, Parrington J, Fissore RA. PLCzeta and its role as a trigger of development in vertebrates. Mol Reprod Dev. 2011 Oct-Nov;78(10-11):846-53. doi: 10.1002/mrd.21359. Epub 2011 Aug 5.
Swann K, Yu Y. The dynamics of calcium oscillations that activate mammalian eggs. Int J Dev Biol. 2008;52(5-6):585-94. doi: 10.1387/ijdb.072530ks.
Publicover S, Harper CV, Barratt C. [Ca2+]i signalling in sperm--making the most of what you've got. Nat Cell Biol. 2007 Mar;9(3):235-42. doi: 10.1038/ncb0307-235.
Swann K, Ozil JP. Dynamics of the calcium signal that triggers mammalian egg activation. Int Rev Cytol. 1994;152:183-222. doi: 10.1016/s0074-7696(08)62557-7. No abstract available.
Kline D, Kline JT. Repetitive calcium transients and the role of calcium in exocytosis and cell cycle activation in the mouse egg. Dev Biol. 1992 Jan;149(1):80-9. doi: 10.1016/0012-1606(92)90265-i.
Alshahrani S, Ahmed AF, Gabr AH, Abalhassan M, Ahmad G. The impact of body mass index on semen parameters in infertile men. Andrologia. 2016 Dec;48(10):1125-1129. doi: 10.1111/and.12549. Epub 2016 Feb 5.
Al-Turki HA. A 5-year analysis of semen parameters in Saudi Arabian men attending infertility clinics. J Int Med Res. 2016 Jun;44(3):656-61. doi: 10.1177/0300060516632108. Epub 2016 Apr 1.
Harton GL, Tempest HG. Chromosomal disorders and male infertility. Asian J Androl. 2012 Jan;14(1):32-9. doi: 10.1038/aja.2011.66. Epub 2011 Nov 28.
Hotaling JM. Genetics of male infertility. Urol Clin North Am. 2014 Feb;41(1):1-17. doi: 10.1016/j.ucl.2013.08.009. Epub 2013 Oct 23.
Gunes S, Arslan MA, Hekim GNT, Asci R. The role of epigenetics in idiopathic male infertility. J Assist Reprod Genet. 2016 May;33(5):553-569. doi: 10.1007/s10815-016-0682-8. Epub 2016 Mar 3.
Pelinck MJ, Hoek A, Simons AH, Heineman MJ, van Echten-Arends J, Arts EG. Embryo quality and impact of specific embryo characteristics on ongoing implantation in unselected embryos derived from modified natural cycle in vitro fertilization. Fertil Steril. 2010 Jul;94(2):527-34. doi: 10.1016/j.fertnstert.2009.03.076. Epub 2009 May 12.
Fauque P, Leandri R, Merlet F, Juillard JC, Epelboin S, Guibert J, Jouannet P, Patrat C. Pregnancy outcome and live birth after IVF and ICSI according to embryo quality. J Assist Reprod Genet. 2007 May;24(5):159-65. doi: 10.1007/s10815-007-9115-z. Epub 2007 Mar 6.
Ramadan WM, Kashir J, Jones C, Coward K. Oocyte activation and phospholipase C zeta (PLCzeta): diagnostic and therapeutic implications for assisted reproductive technology. Cell Commun Signal. 2012 Jul 9;10(1):12. doi: 10.1186/1478-811X-10-12.
Kashir J, Heindryckx B, Jones C, De Sutter P, Parrington J, Coward K. Oocyte activation, phospholipase C zeta and human infertility. Hum Reprod Update. 2010 Nov-Dec;16(6):690-703. doi: 10.1093/humupd/dmq018. Epub 2010 Jun 23.
Planned date reported by the registry; this milestone is not confirmed as achieved.
Study Completion
August 2027
EstimatedPlanned date reported by the registry; this milestone is not confirmed as achieved.
Last Updated
July 6, 2026
Record last verified: 2026-06
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