{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:37:57Z","timestamp":1790285877145,"version":"4.1.0"},"reference-count":206,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Khalifa University","award":["FSU-2023-15"],"award-info":[{"award-number":["FSU-2023-15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Oocyte activation, a fundamental event during mammalian fertilisation, is initiated by concerted intracellular patterns of calcium (Ca2+) release, termed Ca2+ oscillations, predominantly driven by testis-specific phospholipase C zeta (PLC\u03b6). Ca2+ exerts a pivotal role in not just regulating oocyte activation and driving fertilisation, but also in influencing the quality of embryogenesis. In humans, a failure of Ca2+ release, or defects in related mechanisms, have been reported to result in infertility. Furthermore, mutations in the PLC\u03b6 gene and abnormalities in sperm PLC\u03b6 protein and RNA, have been strongly associated with forms of male infertility where oocyte activation is deficient. Concurrently, specific patterns and profiles of PLC\u03b6 in human sperm have been linked to parameters of semen quality, suggesting the potential for PLC\u03b6 as a powerful target for both therapeutics and diagnostics of human fertility. However, further to PLC\u03b6 and given the strong role played by Ca2+ in fertilisation, targets down- and up-stream of this process may also present a significantly similar level of promise. Herein, we systematically summarise recent advancements and controversies in the field to update expanding clinical associations between Ca2+-release, PLC\u03b6, oocyte activation and human fertility. We discuss how such associations may potentially underlie defective embryogenesis and recurrent implantation failure following fertility treatments, alongside potential diagnostic and therapeutic avenues presented by oocyte activation for the diagnosis and treatment of human infertility.<\/jats:p>","DOI":"10.3390\/ph16030441","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:22:59Z","timestamp":1678857779000},"page":"441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Therapeutic and Diagnostic Potential of Phospholipase C Zeta, Oocyte Activation, and Calcium in Treating Human Infertility"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-3254","authenticated-orcid":false,"given":"Haia M. R.","family":"Abdulsamad","sequence":"first","affiliation":[{"name":"Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoha F.","family":"Murtaza","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hessa M.","family":"AlMuhairi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wjdan S.","family":"Bafleh","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma A.","family":"AlMansoori","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaikha A.","family":"AlQubaisi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2029-6772","authenticated-orcid":false,"given":"Hamdan","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5056-8222","authenticated-orcid":false,"given":"Junaid","family":"Kashir","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Arts and Science, Khalifa University, Abu Dhabi 127788, United Arab Emirates"},{"name":"Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 12713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/humupd\/8.4.313","article-title":"Signalling mechanisms of mammalian oocyte activation","volume":"8","author":"Williams","year":"2002","journal-title":"Hum. 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