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Endocytosis of sialic acid Neu5Gc and elevated p53 contributes to preimplantation embryonic arrest during in vitro fertilization

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机构： [1]Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China [2]Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China. [3]Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, Duarte, California, USA [4]Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China. [5]Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

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The persistently low success rate of human in vitro fertilization (IVF) remains a major clinical challenge, despite significant technological advancements. While culture media composition is known to influence outcomes, the specific components affecting embryonic development are poorly understood. In this study, we identify N-glycolylneuraminic acid (Neu5Gc), a foreign sialic acid contaminant prevalent in animal-derived IVF media components, as a micro-environmental factor triggering developmental arrest. We demonstrate that Neu5Gc accumulates in arrested human embryos via endocytosis and upregulates p53, leading to caspase-3/PARP -dependent apoptotic pathways. This mechanism was validated in human embryonic stem cells (hESCs) and zebrafish embryos, with antibody-mediated Neu5Gc neutralization rescuing developmental defects. Our findings not only elucidate a novel pathway contributing to IVF inefficiency but also provide actionable insights for optimizing culture media formulations.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

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大类 | 2 区生物学

小类 | 2 区生化与分子生物学

最新[2025]版：

大类 | 2 区生物学

小类 | 2 区生化与分子生物学

第一作者：

第一作者机构： [1]Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China [2]Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

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通讯机构： [1]Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China [2]Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China. [3]Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, Duarte, California, USA [4]Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China. [5]Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

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