{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:43:32Z","timestamp":1790243012149,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"C\u00e1tedra Human Fertility (A-GE-C\u00e1tedra Human Fertility 35.90.6Q..00.01) and Departamento de Biotecnolog\u00eda of the Universidad de Alicante","award":["VIGROB-186"],"award-info":[{"award-number":["VIGROB-186"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During fertilization, the fusion of the spermatozoa with the oocytes causes the release of calcium from the oocyte endoplasmatic reticulum. This, in turn, triggers a series of calcium ion (Ca2+) oscillations, a process known as oocyte activation. The sperm-specific factor responsible for oocyte activation is phospholipase C zeta (PLC\u03b6). Men undergoing intracytoplasmic sperm injection (ICSI) with their spermatozoa lacking PLC\u03b6 are incapable of generating Ca2+ oscillation, leading to fertilization failure. The immunofluorescence assay is the most used technique to assess the expression and localization of PLC\u03b6 and to diagnose patients with reduced\/absent ability to activate the oocytes. In these patients, the use of assisted oocyte activation (AOA) technique can help to yield successful ICSI results and shorten the time of pregnancy. However, the production of a stable PLC\u03b6 recombinant protein represents a new powerful therapeutic approach to treating individuals with this condition. We aim to conduct a systematic review focusing on the expression, level, and localization of PLC\u03b6, discussing the novel genetic mutation associated with its impairment. In addition, we highlight the benefits of AOA, looking at new and less invasive methods to diagnose and treat cases with PLC\u03b6 dysfunction.<\/jats:p>","DOI":"10.3390\/ijms25021344","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T11:36:41Z","timestamp":1705923401000},"page":"1344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Phospholipase C Zeta in Human Spermatozoa: A Systematic Review on Current Development and Clinical Application"],"prefix":"10.3390","volume":"25","author":[{"given":"Alessandra","family":"Parrella","sequence":"first","affiliation":[{"name":"IVF Life, Reproductive Medicine, 03540 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llanos","family":"Medrano","sequence":"additional","affiliation":[{"name":"IVF Life, Reproductive Medicine, 03540 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Aizpurua","sequence":"additional","affiliation":[{"name":"IVF Life, Reproductive Medicine, 03540 Alicante, Spain"},{"name":"C\u00e1tedra Human Fertility, Facultad de Ciencias, Universidad de Alicante, 03690 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2384-8154","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"G\u00f3mez-Torres","sequence":"additional","affiliation":[{"name":"C\u00e1tedra Human Fertility, Facultad de Ciencias, Universidad de Alicante, 03690 Alicante, Spain"},{"name":"Departamento de Biotecnolog\u00eda, Facultad de Ciencias, Universidad de Alicante, 03690 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"F53","DOI":"10.1530\/REP-21-0458","article-title":"SPERM FACTORS AND EGG ACTIVATION: Phospholipase C Zeta (PLCZ1) and the Clinical Diagnosis of Oocyte Activation Deficiency","volume":"164","author":"Jones","year":"2022","journal-title":"Reproduction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1007\/s10815-021-02191-4","article-title":"Single-Center Thorough Evaluation and Targeted Treatment of Globozoospermic Men","volume":"38","author":"Cheung","year":"2021","journal-title":"J. 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