{"paper_id":"7924e569-0dcd-477d-9205-5132b12e912a","body_text":"Abstract\nBackground\nEndometriosis is a chronic inflammatory disease strongly associated with reduced oocyte quality and subfertility, yet the underlying cytoplasmic defects remain poorly understood.\nMethods\nUsing a surgically induced autologous mouse model, we examined whether endometriosis alters oocyte metabolism, cortical granule (CG) biology, actin architecture, SNARE-regulated exocytosis, fertilization, and early embryonic activation.\nResults\nEndometriosis markedly increased intracellular reactive oxygen species and altered quinacrine-positive acidic vesicular compartments in ovulated oocytes. Although CG localization was preserved, endometriotic oocytes failed to undergo strontium chloride–induced CG exocytosis. These defects correlated with a significantly thickened cortical F-actin cytoskeleton and a substantial reduction in α-SNAP and NSF levels—two essential regulators of SNARE complex disassembly and membrane fusion. Functionally, endometriotic oocytes exhibited decreased fertilization rates without evidence of polyspermy, while their ability to undergo TPEN-induced parthenogenetic activation and second polar body extrusion remained unchanged.\nConclusions\nThese findings demonstrate that endometriosis impairs multiple aspects of cytoplasmic maturation—metabolic homeostasis, actin remodeling, and CG exocytotic machinery—ultimately reducing sperm–oocyte fusion efficiency while preserving early embryonic activation capacity. This mechanistic insight provides a foundation for understanding how endometriosis compromises oocyte competence.\nSimilar content being viewed by others\nAbbreviations\n- α-SNAP:\n-\nAlpha-soluble NSF attachment protein\n- BS:\n-\nBlocking solution\n- BSA:\n-\nBovine serum albumin\n- CCCP:\n-\nCarbonyl cyanide 3-chlorophenylhydrazone\n- CG:\n-\nCortical granule\n- CGE:\n-\nCortical granule exocytosis\n- COCs:\n-\nCumulus–oocyte complexes\n- DCF-DA:\n-\nDichlorofluorescin diacetate\n- DPBS:\n-\nDulbecco’s phosphate-buffered saline\n- Endo:\n-\nEndometriosis group\n- F-actin:\n-\nFilamentous actin\n- GV:\n-\nGerminal vesicle\n- hCG:\n-\nHuman chorionic gonadotropin\n- HTF:\n-\nHuman Tubal Fluid medium\n- i.p.:\n-\nIntraperitoneally\n- IVF:\n-\nIn vitro fertilization\n- LCA-FITC:\n-\nLens Culinaris Agglutinin labeled with Fluorescein Isothiocyanate\n- MII:\n-\nMetaphase II\n- MMP:\n-\nMitochondrial membrane potential\n- NSF:\n-\nN-ethylmaleimide-sensitive factor\n- PBS:\n-\nPhosphate-buffered saline\n- PFA:\n-\nParaformaldehyde\n- PMSG:\n-\nPurified equine chorionic gonadotropin\n- PVA:\n-\nPolyvinyl alcohol\n- ROS:\n-\nReactive oxygen species\n- RT:\n-\nRoom temperature\n- SEM:\n-\nStandard Error of the Mean\n- SNARE:\n-\nSoluble N-ethylmaleimide-sensitive factor Attachment protein Receptor\n- SrCl2:\n-\nStrontium chloride\n- TMRE:\n-\nt-ditetramethyl rhodamine methyl ester\n- TPEN:\n-\nN,N,N′,N′-Tetrakis (2-pyridylmethyl) ethylenediamine\nAcknowledgements\nThe authors are very grateful to Dr. Marilina Casais (Instituto Multidisciplinario de Investigaciones Biológicas de San Luis, Universidad Nacional de San Luis-CONICET, San Luis, Argentina) for her instruction in the development of the endometriosis model used in this work. The authors acknowledge the help of Veterinarian Julieta Scelta in the maintenance of the animal facility and Engr. Elisa Bocanegra and Dr. Jorge Ibáñez for excellent technical assistance (IHEM, UNCUYO-CONICET, Mendoza, Argentina). OGK, PAW and ECA are thankful to CONICET, Argentina, for fellowships. JER is thankful to Agencia I+D+i, Argentina, for his fellowship.\nFunding\nThis work was funded by Agencia Nacional de Promoción Científica y Tecnológica (grant PICT 2020–03627 to MAM), Argentina, and Universidad Nacional de Cuyo (grants 06/M025-T1, J050-T1, PIO 80020230100017 N, and 06/80020240400085UN to MAM; 80020240200084UN to ECA), Mendoza, Argentina.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nEthics approval and consent to participate\nAll experimental procedures were performed in accordance with the Guiding Principles in the Care and Use of Animals of the US National Institutes of Health. Protocols were approved by the Institutional Animal Care and Use Committee of the School of Medical Science, Universidad Nacional de Cuyo (Protocol No. 227/2022).\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSupplementary Information\nRights and permissions\nOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/.\nAbout this article\nCite this article\nKlinsky, O.G., Wetten, P.A., Romani, J.E. et al. Endometriosis disrupts oocyte metabolism and cortical granule function, impairing fertilization. Reprod Biol Endocrinol (2026). https://doi.org/10.1186/s12958-026-01571-8\nReceived:\nAccepted:\nPublished:\nDOI: https://doi.org/10.1186/s12958-026-01571-8","source_license":"CC0","license_restricted":false}