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Publications

Journal Article Ppublish

PubMed: 40404013 DOI: 10.1016/j.jbc.2025.110254

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

J Biol Chem 301(6):110254

Authors: Xin Yuan, Yilun Wu, Yi Zhang, Bin Yao, Linyu Zhang, Zhenqing Liu, Qianhong Ma, Fang Ma

Affiliations

  • 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; Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Department of Neurodegenerative Diseases, Beckman Research Institute of City of Hope, Duarte, California, USA; Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China; 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.
  • 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; Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Abstract

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.

MeSH

Human Embryonic Stem Cells, N-Acetylneuraminic Acid, Biochemistry, Culture Media, Embryonic Development, Fertilization In Vitro, Fertilization, Endocytosis