Yuan Xin, Wu Yilun, Zhang Yi, Yao Bin, Zhang Linyu, Liu Zhenqing, Ma Qianhong, Ma Fang
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.
J Biol Chem. 2025 May 20;301(6):110254. doi: 10.1016/j.jbc.2025.110254.
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.
尽管技术取得了重大进步，但人类体外受精（IVF）的成功率持续偏低仍是一项重大临床挑战。虽然已知培养基成分会影响结果，但对影响胚胎发育的具体成分却知之甚少。在本研究中，我们确定了N-羟乙酰神经氨酸（Neu5Gc），一种在动物源性IVF培养基成分中普遍存在的外来唾液酸污染物，是触发发育停滞的微环境因素。我们证明Neu5Gc通过内吞作用在停滞的人类胚胎中积累，并上调p53，导致半胱天冬酶-3/聚（ADP-核糖）聚合酶（PARP）依赖性凋亡途径。这一机制在人类胚胎干细胞（hESC）和斑马鱼胚胎中得到验证，抗体介导的Neu5Gc中和可挽救发育缺陷。我们研究结果不仅阐明了导致IVF效率低下的新途径，还为优化培养基配方提供了可行的见解。
