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dc.contributor.authorAarabi, Mahmouden
dc.date2013-09-29 23:45:35.395
dc.date.accessioned2013-10-01T19:02:39Z
dc.date.available2016-06-26T08:00:05Z
dc.date.issued2013-10-01
dc.identifier.urihttp://hdl.handle.net/1974/8354
dc.descriptionThesis (Ph.D, Anatomy & Cell Biology) -- Queen's University, 2013-09-29 23:45:35.395en
dc.description.abstractSuccessful fertilization depends upon the activation of metaphase II arrested oocytes by sperm-borne oocyte activating factor (SOAF). Failure of oocyte activation is considered as the cause of treatment failure in a proportion of infertile couples. SOAF induces the release of intracellular calcium in oocyte which leads to meiotic resumption and pronuclear formation. Calcium release is either in the form of single calcium transient in echinoderm and amphibian oocytes or several calcium oscillations in ascidian and mammalian oocytes. Although the SOAF attributes are established, it is not clear which sperm protein(s) play such role. Sperm postacrosomal WW binding protein (PAWP) satisfies a developmental criteria set for a candidate SOAF. This study shows that recombinant human PAWP protein or its transcript acts upstream of calcium release and fully activates the amphibian and mammalian oocytes. Interference trials provided evidence for the first time that PAWP mediates sperm-induced intracellular calcium release through a PPXY/WWI domain module in Xenopus, mouse and human oocytes. Clinical applications of PAWP were further investigated by prospective study on the sperm samples from patients undergoing intracytoplasmic sperm injection (ICSI). PAWP expression level, analyzed by flow cytometry, was correlated to ICSI success rate and embryonic development. This study also explored the developmental expression of the other SOAF candidate, PLCζ in male reproductive system and its function during fertilization. Our findings showed for the first time that PLCζ most likely binds to the sperm head surface during epididymal passage and is expressed in epididymis. We demonstrated that PLCζ is also compartmentalized early in spermiogenesis and thus could play an important role during spermiogenesis. Detailed analysis of in vitro fertilization revealed that PLCζ disappears from sperm head during acrosome reaction and is not detectable during sperm incorporation into the oocyte cytoplasm. In conclusion, this dissertation provides evidence for the essential non-redundant role of sperm PAWP in amphibian and mammalian fertilization; recommends PAWP as a biomarker for prediction of ICSI outcomes in infertile couples; and proposes that sperm PLCζ may have functions other than inducing oocyte activation during fertilization.en
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectPLCzen
dc.subjectFertilizationen
dc.subjectSpermen
dc.subjectYAPen
dc.subjectWWI Domainen
dc.subjectOocyte Activationen
dc.subjectIntracytoplasmic Sperm Injectionen
dc.subjectAssisted Reproductive Technologiesen
dc.subjectInfertilityen
dc.subjectPAWPen
dc.titleA Functional, Comparative and Clinical Analysis of Sperm-Borne Oocyte Activating Factor, PAWPen
dc.typethesisen
dc.description.restricted-thesisWe have current patents as well as publications under review for this thesis. Therefore, this document is highly confidential and needs to be restricted from access at the moment.en
dc.description.degreePhDen
dc.contributor.supervisorOko, Richarden
dc.contributor.departmentAnatomy and Cell Biologyen
dc.embargo.terms1825en
dc.degree.grantorQueen's University at Kingstonen


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