The proteostatic landscape of healthy human oocytes

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• dc.contributor.author Zaffagnini, Gabriele
• dc.contributor.author Solé, Miquel
• dc.contributor.author Duran, Juan M.
• dc.contributor.author Polyzos, Nikolaos P.
• dc.contributor.author Böke, Elvan
• dc.date.accessioned 2025-10-09T13:00:43Z
• dc.date.available 2025-10-09T13:00:43Z
• dc.date.issued 2025
• dc.date.updated 2025-10-09T13:00:43Z
• dc.description.abstract Oocytes, female germ cells that develop into eggs, are among the longest-lived cells in the animal body. Recent studies on mouse oocytes highlight unique adaptations in protein homeostasis (proteostasis) within these cells. However, the mechanisms of proteostasis in human oocytes remain virtually unstudied. We present the first large-scale study of proteostatic activity in human oocytes using over 100 freshly donated oocytes from 21 healthy women aged 19-34 years. We analysed the activity and distribution of lysosomes, proteasomes, and mitochondria in both immature and mature oocytes. Notably, human oocytes exhibit nearly twofold lower proteolytic activity than surrounding somatic cells, with further decreases as oocytes mature. Oocyte maturation is also coupled with lysosomal exocytosis and a decrease in mitochondrial membrane potential. We propose that reduced organelle activity preserves key cellular components critical for early embryonic development during the prolonged maturation of human oocytes. Our findings highlight the distinctive biology of human oocytes and the need to investigate human-specific reproductive biology to address challenges in female fertility.
• dc.description.sponsorship We are grateful to the CRG Advanced Light Microscopy Units for the support and assistance in this work. E.B. acknowledges institutional core funding and the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033) and the Generalitat de Catalunya through the CERCA programme, the Ministerio de Ciencia e Innovación PID2023-146697NB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER, UE and the Vallee Scholar Award (Vallee Foundation Inc).
• dc.format.mimetype application/pdf
• dc.identifier.citation Zaffagnini G, Solé M, Duran JM, Polyzos NP, Böke E. The proteostatic landscape of healthy human oocytes. EMBO J. 2025 Aug;44(16):4611-30. DOI: 10.1038/s44318-025-00493-2
• dc.identifier.doi http://dx.doi.org/10.1038/s44318-025-00493-2
• dc.identifier.issn 0261-4189
• dc.identifier.uri http://hdl.handle.net/10230/71454
• dc.language.iso eng
• dc.publisher EMBO Press
• dc.relation.ispartof The EMBO Journal. 2025;44(16):4611-4630
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2023-146697NB-I00
• dc.rights © 2025 The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Female fertility
• dc.subject.keyword Human oocytes
• dc.subject.keyword Lysosomes
• dc.subject.keyword Mitochondria
• dc.subject.keyword Proteostasis
• dc.title The proteostatic landscape of healthy human oocytes
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion