{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWBP2NL, also known as PAWP, is a protein localized to the post‐acrosomal region of mammalian spermatozoa that was originally proposed as a sperm‐borne oocyte activating factor (SOAF), purported to trigger the Ca²⁺ oscillations essential for oocyte activation and the initiation of embryo development. Intriguingly, beyond its putative reproductive role, altered expression of WBP2NL has been observed in breast cancer tissues, suggesting that it may also function as an anti‐apoptotic factor or co‐activator promoting tumor cell survival and proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed functional studies, however, have produced divergent results regarding its ability to induce oocyte activation. Several investigations have demonstrated that microinjection of human PAWP protein or its corresponding cRNA fails to elicit the characteristic Ca²⁺ oscillations normally seen at fertilization, with the sperm‐specific phospholipase C‑zeta (PLCZ1) emerging as the more potent activator. Consistent with this, in patients where deleterious mutations in PLCZ1 resulted in fertilization failure, PAWP expression and localization were found to be normal, indicating that PAWP is not sufficient to compensate for the absence of functional PLCZ1. Moreover, studies in conditions such as globozoospermia have reported that reduced mRNA and protein levels of PAWP are associated with a lower fertilization potential, while sperm processing techniques further modulate its detectable levels."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinical evaluations of WBP2NL/PAWP in the context of assisted reproduction have yielded mixed findings. Although analyses of infertile men with conditions such as oligoasthenoteratozoospermia reveal a lower proportion of PAWP-positive sperm, comprehensive assessments in patients undergoing intracytoplasmic sperm injection (ICSI) have not established a clear relationship between PAWP protein levels or distribution and fertilization outcomes. These observations, collectively, underscore that while WBP2NL/PAWP may be involved in the ensemble of sperm factors contributing to fertilization—and even in oncogenic regulation—its role as the critical inducer of oocyte activation remains contentious."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mahmoud Aarabi, Hanna Balakier, Siamak Bashar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sperm content of postacrosomal WW binding protein is related to fertilization outcomes in patients undergoing assisted reproductive technology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2014.05.003"}], "href": "https://doi.org/10.1016/j.fertnstert.2014.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24907910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24907910"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Seyedmehdi Nourashrafeddin, Mahmoud Aarabi, Mohammad Hosein Modarressi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Evaluation of WBP2NL-Related Genes Expression in Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Oncol Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12253-014-9820-8"}], "href": "https://doi.org/10.1007/s12253-014-9820-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25417742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25417742"}]}, {"type": "r", "ref": 3, "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": 4, "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": 5, "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": 6, "children": [{"type": "t", "text": "M Tavalaee, M H Nasr-Esfahani "}, {"type": "b", "children": [{"type": "t", "text": "Expression profile of PLCζ, PAWP, and TR-KIT in association with fertilization potential, embryo development, and pregnancy outcomes in globozoospermic candidates for intra-cytoplasmic sperm injection and artificial oocyte activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Andrology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/andr.12179"}], "href": "https://doi.org/10.1111/andr.12179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27089467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27089467"}]}, {"type": "r", "ref": 7, "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": 8, "children": [{"type": "t", "text": "T Freour, M Barragan, A Ferrer-Vaquer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WBP2NL/PAWP mRNA and protein expression in sperm cells are not related to semen parameters, fertilization rate, or reproductive outcome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-017-0902-x"}], "href": "https://doi.org/10.1007/s10815-017-0902-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28444612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28444612"}]}, {"type": "r", "ref": 9, "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": 10, "children": [{"type": "t", "text": "Thomas Freour, Montserrat Barragan, Marc Torra-Massana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Is there an association between PAWP/WBP2NL sequence, expression, and distribution in sperm cells and fertilization failures in ICSI cycles?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Reprod Dev (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mrd.22950"}], "href": "https://doi.org/10.1002/mrd.22950"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29271520"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29271520"}]}]}]}