{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPhospholipase C zeta 1 (PLCZ1) is a sperm‐specific enzyme that plays an essential role in initiating oocyte activation at fertilization. Delivered by the sperm at gamete fusion, PLCZ1 hydrolyzes phosphatidylinositol 4,5‐bisphosphate (PIP2) to produce inositol 1,4,5‐trisphosphate (IP3), thereby triggering the characteristic intracellular Ca²⁺ oscillations required for the completion of meiosis, pronuclear formation, and the onset of embryogenesis. Work across mammalian and non‐mammalian species has further underscored that timely expression, proper intracellular trafficking, and nuclear translocation (or sequestration) of PLCZ1 are critical for a normal fertilization process and subsequent embryonic development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in PLCZ1 expression, structure, or localization have been strongly associated with various forms of male infertility, including oocyte activation deficiency and total fertilization failure encountered during assisted reproductive treatments. Multiple studies have identified pathogenic point mutations and genetic variants within key functional domains—such as the catalytic regions, EF‐hand motifs, and the C2 domain—that impair enzymatic activity and disrupt the induction of Ca²⁺ oscillations. In parallel, analyses of sperm from infertile patients (including cases of globozoospermia and idiopathic infertility) have revealed abnormal PLCZ1 immunolocalization and a quantitative reduction in its expression, establishing the protein’s value as a diagnostic biomarker. Moreover, molecular evaluations, ranging from in vitro PIP2 hydrolysis assays to in vivo Ca²⁺ oscillation rescue experiments using PLCZ1 mRNA/protein, have provided compelling evidence linking its deficiency or dysfunction to failed oocyte activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOngoing research into the structure–function relationships of PLCZ1 has revealed species‐specific differences in its Ca²⁺ oscillatory potency and clarified the critical importance of its unique domains—such as the EF‐hand for calcium sensitivity and the C2 domain for membrane/lipid targeting. In parallel, studies contrasting PLCZ1 with other putative sperm factors (e.g. PAWP) have reinforced that only PLCZ1 consistently recapitulates the full spectrum of Ca²⁺ oscillations observed at fertilization. These advances have spawned novel diagnostic assays and therapeutic strategies, including the use of recombinant protein or mRNA microinjection to rescue oocyte activation deficits, ultimately offering promising avenues to ameliorate fertilization failure in clinical settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "38", "end_ref": "46"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sook-Young Yoon, Teru Jellerette, Ana Maria Salicioni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI36942"}], "href": "https://doi.org/10.1172/JCI36942"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18924610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18924610"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jessica Escoffier, Hoi Chang Lee, Sandra Yassine, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddv617"}], "href": "https://doi.org/10.1093/hmg/ddv617"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26721930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26721930"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Masahiko Ito, Tomohide Shikano, Shoji Oda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.108.067801"}], "href": "https://doi.org/10.1095/biolreprod.108.067801"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18322275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18322275"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Michail Nomikos, Junaid Kashir, Karl Swann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sperm PLCζ: from structure to Ca2+ oscillations, egg activation and therapeutic potential."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2013.10.008"}], "href": "https://doi.org/10.1016/j.febslet.2013.10.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24157362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24157362"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Y Yu, C M Saunders, F A Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Preimplantation development of mouse oocytes activated by different levels of human phospholipase C zeta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dem350"}], "href": "https://doi.org/10.1093/humrep/dem350"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18003622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18003622"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Junaid Kashir, Michail Nomikos, F Anthony Lai "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase C zeta and calcium oscillations at fertilisation: The evidence, applications, and further questions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Biol Regul (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbior.2017.10.012"}], "href": "https://doi.org/10.1016/j.jbior.2017.10.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29108881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29108881"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Michail Nomikos "}, {"type": "b", "children": [{"type": "t", "text": "Novel signalling mechanism and clinical applications of sperm-specific PLCζ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST20140291"}], "href": "https://doi.org/10.1042/BST20140291"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26009178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26009178"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Takashi Yamaguchi, Masahiko Ito, Keiji Kuroda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The establishment of appropriate methods for egg-activation by human PLCZ1 RNA injection into human oocyte."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Calcium (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ceca.2017.03.002"}], "href": "https://doi.org/10.1016/j.ceca.2017.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28320563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28320563"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alessandra Parrella, Llanos Medrano, Jon Aizpurua, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase C Zeta in Human Spermatozoa: A Systematic Review on Current Development and Clinical Application."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms25021344"}], "href": "https://doi.org/10.3390/ijms25021344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38279344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38279344"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Junaid Kashir, Michalis Konstantinidis, Celine Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/der384"}], "href": "https://doi.org/10.1093/humrep/der384"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22095789"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22095789"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Siti Nornadhirah Amdani, Celine Jones, Kevin Coward "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase C zeta (PLCζ): oocyte activation and clinical links to male factor infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Biol Regul (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbior.2013.07.005"}], "href": "https://doi.org/10.1016/j.jbior.2013.07.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23916605"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23916605"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Suseela Yelumalai, Marc Yeste, Celine Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta are significantly correlated with fertilization rates after intracytoplasmic sperm injection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2015.05.018"}], "href": "https://doi.org/10.1016/j.fertnstert.2015.05.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26054556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26054556"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "S Aghajanpour, K Ghaedi, A Salamian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative expression of phospholipase C zeta, as an index to assess fertilization potential of a semen sample."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/der285"}], "href": "https://doi.org/10.1093/humrep/der285"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21896550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21896550"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Marc Torra-Massana, David Cornet-Bartolomé, Montserrat Barragán, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel phospholipase C zeta 1 mutations associated with fertilization failures after ICSI."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dez094"}], "href": "https://doi.org/10.1093/humrep/dez094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31347677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31347677"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Michail Nomikos, Khalil Elgmati, Maria Theodoridou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Male infertility-linked point mutation disrupts the Ca2+ oscillation-inducing and PIP(2) hydrolysis activity of sperm PLCζ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20101772"}], "href": "https://doi.org/10.1042/BJ20101772"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21204786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21204786"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Junaid Kashir, Michalis Konstantinidis, Celine Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of two heterozygous mutations of the oocyte activation factor phospholipase C zeta (PLCζ) from an infertile man by use of minisequencing of individual sperm and expression in somatic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2012.05.002"}], "href": "https://doi.org/10.1016/j.fertnstert.2012.05.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22633260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22633260"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Karl Swann, Shane Windsor, Karen Campbell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase C-ζ-induced Ca2+ oscillations cause coincident cytoplasmic movements in human oocytes that failed to fertilize after intracytoplasmic sperm injection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2011.12.013"}], "href": "https://doi.org/10.1016/j.fertnstert.2011.12.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22217962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22217962"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jing Dai, Tianlei Zhang, Jing Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2021.02.004"}], "href": "https://doi.org/10.1016/j.ajhg.2021.02.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33626338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33626338"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Mahmoud Aarabi, Yang Yu, Wei Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The testicular and epididymal expression profile of PLCζ in mouse and human does not support its role as a sperm-borne oocyte activating factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0033496"}], "href": "https://doi.org/10.1371/journal.pone.0033496"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22428063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22428063"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Marziyeh Tavalaee, Michail Nomikos, F Anthony Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of sperm PLCζ and clinical outcomes of ICSI-AOA in men affected by globozoospermia due to DPY19L2 deletion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Biomed Online (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.rbmo.2017.12.013"}], "href": "https://doi.org/10.1016/j.rbmo.2017.12.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29339016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29339016"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Siti Nornadhirah Amdani, Marc Yeste, Celine Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase C zeta (PLCζ) and male infertility: Clinical update and topical developments."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Biol Regul (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbior.2015.11.009"}], "href": "https://doi.org/10.1016/j.jbior.2015.11.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26700242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26700242"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Junaid Kashir, Nathalie Sermondade, Christophe Sifer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Motile sperm organelle morphology evaluation-selected globozoospermic human sperm with an acrosomal bud exhibits novel patterns and higher levels of phospholipase C zeta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/des312"}], "href": "https://doi.org/10.1093/humrep/des312"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22940771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22940771"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Michail Nomikos, Jessica R Sanders, Junaid Kashir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional disparity between human PAWP and PLCζ in the generation of Ca2+ oscillations for oocyte activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gav034"}], "href": "https://doi.org/10.1093/molehr/gav034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26116451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26116451"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Zheng Yan, Yong Fan, Fei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations in PLCZ1 cause male infertility due to fertilization failure or poor fertilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dez282"}], "href": "https://doi.org/10.1093/humrep/dez282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32048714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32048714"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Jing Dai, Can Dai, Jing Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel homozygous variations in PLCZ1 lead to poor or failed fertilization characterized by abnormal localization patterns of PLCζ in sperm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13636"}], "href": "https://doi.org/10.1111/cge.13636"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31463947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31463947"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Jian Mu, Zhihua Zhang, Ling Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The identification of novel mutations in PLCZ1 responsible for human fertilization failure and a therapeutic intervention by artificial oocyte activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gaaa003"}], "href": "https://doi.org/10.1093/molehr/gaaa003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31953539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31953539"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Junaid Kashir, Michail Nomikos, Karl Swann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLCζ or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gav009"}], "href": "https://doi.org/10.1093/molehr/gav009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25722320"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25722320"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Naoko Yoshida, Manami Amanai, Tomoyuki Fukui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Broad, ectopic expression of the sperm protein PLCZ1 induces parthenogenesis and ovarian tumours in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.007930"}], "href": "https://doi.org/10.1242/dev.007930"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17933795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17933795"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Hoi Chang Lee, Margaret Arny, Daniel Grow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phospholipase C Zeta1 expression in patients with failed ICSI but with normal sperm parameters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-014-0229-9"}], "href": "https://doi.org/10.1007/s10815-014-0229-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24756570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24756570"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Michail Nomikos, Maria Theodoridou, Khalil Elgmati, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human PLCζ exhibits superior fertilization potency over mouse PLCζ in triggering the Ca(2+) oscillations required for mammalian oocyte activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gau011"}], "href": "https://doi.org/10.1093/molehr/gau011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24478462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24478462"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Xin Meng, Pedro Melo, Celine Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2020.02.113"}], "href": "https://doi.org/10.1016/j.fertnstert.2020.02.113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32622408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32622408"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Michail Nomikos, Panagiotis Stamatiadis, Jessica R Sanders, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Male infertility-linked point mutation reveals a vital binding role for the C2 domain of sperm PLCζ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20161057"}], "href": "https://doi.org/10.1042/BCJ20161057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28270562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28270562"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Peng Yuan, Cen Yang, Yixin Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel homozygous mutation of phospholipase C zeta leading to defective human oocyte activation and fertilization failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dez293"}], "href": "https://doi.org/10.1093/humrep/dez293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32142120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32142120"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Junaid Kashir "}, {"type": "b", "children": [{"type": "t", "text": "Increasing associations between defects in phospholipase C zeta and conditions of male infertility: not just ICSI failure?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-020-01748-z"}], "href": "https://doi.org/10.1007/s10815-020-01748-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32285298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32285298"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep27543"}], "href": "https://doi.org/10.1038/srep27543"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27270687"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27270687"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Elham Janghorban-Laricheh, Nasim Ghazavi-Khorasgani, Marziyeh Tavalaee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An association between sperm PLCζ levels and varicocele?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-016-0802-5"}], "href": "https://doi.org/10.1007/s10815-016-0802-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27612872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27612872"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Pegah Rahimizadeh, Tohid Rezaei Topraggaleh, Mohammad Hossein Nasr-Esfahani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The alteration of PLCζ protein expression in unexplained infertile and asthenoteratozoospermic patients: A potential effect on sperm fertilization ability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Reprod Dev (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mrd.23293"}], "href": "https://doi.org/10.1002/mrd.23293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31736165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31736165"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Ping Yuan, Lingyan Zheng, Hao Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations in the PLCZ1 gene associated with human low or failed fertilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.1470"}], "href": "https://doi.org/10.1002/mgg3.1470"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32840018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32840018"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Zahabiya H Chithiwala, Hoi Chang Lee, David L Hill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-015-0531-1"}], "href": "https://doi.org/10.1007/s10815-015-0531-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26174123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26174123"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Fengsong Wang, Jingjing Zhang, Shuai Kong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A homozygous nonsense mutation of PLCZ1 cause male infertility with oocyte activation deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-020-01719-4"}], "href": "https://doi.org/10.1007/s10815-020-01719-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32146562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32146562"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Nahid Azad, Hamid Nazarian, Marefat Ghaffari Novin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oligoasthenoteratozoospermic (OAT) men display altered phospholipase C ζ (PLCζ) localization and a lower percentage of sperm cells expressing PLCζ and post-acrosomal sheath WW domain-binding protein (PAWP)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bosn J Basic Med Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.17305/bjbms.2017.2208"}], "href": "https://doi.org/10.17305/bjbms.2017.2208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28954204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28954204"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Shuai Zhao, Ying Cui, Shunli Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel variants in ACTL7A and PLCZ1 are associated with male infertility and total fertilization failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.14293"}], "href": "https://doi.org/10.1111/cge.14293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36593593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36593593"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Jin Xia Zhu, Ning Yang, Hu Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of NYD-SP27 down-regulation on ATP-induced Ca2+-dependent pancreatic duct anion secretion in cystic fibrosis cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellbi.2006.11.021"}], "href": "https://doi.org/10.1016/j.cellbi.2006.11.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17196844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17196844"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Marziyeh Tavalaee, Kazem Parivar, Abdol-Hossein Shahverdi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Status of sperm-born oocyte activating factors (PAWP, PLCζ) and sperm chromatin in uncapacitated, capacitated and acrosome-reacted conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Fertil (Camb) (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/14647273.2016.1264011"}], "href": "https://doi.org/10.1080/14647273.2016.1264011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28076980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28076980"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Xin Meng, Celine Jones, Pedro Melo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antigen unmasking does not improve the visualization of phospholipase C zeta in human spermatozoa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Asian J Androl (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4103/aja202168"}], "href": "https://doi.org/10.4103/aja202168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34893574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34893574"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Ke-Ya Tong, Wei-Wei Liu, Li-Wei Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel PLCZ1 mutation caused polyspermy during in vitro fertilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Asian J Androl (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4103/aja202376"}], "href": "https://doi.org/10.4103/aja202376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38445955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38445955"}]}]}]}