北京生命科学研究所苏俊小组近日取得一项新成果。经过不懈努力,他们的最新研究探明了两个不同的原因导致人类植入前发育的低效率。2026年6月11日出版的《细胞》杂志发表了这项成果。
通过对150个人类和猴子受精卵进行长达5天的成像,研究人员发现第二次有丝分裂是最容易出错的,这解释了早期胚胎停滞的原因。随机中心粒过度复制可以通过PLK4抑制剂中心酮的短暂治疗有效抑制,使2细胞卵裂球易于组装多极纺锤体和染色体错离。错误分离的染色体反过来导致人类胚胎中大多数微核的形成,并导致子卵裂球的停滞或死亡。相比之下,胚胎晚期停滞在很大程度上与染色体错离无关,但涉及内质网应激反应的激活,这可能会损害胚泡形成所需的连接蛋白和细胞极性蛋白亚群的表达。这两种不同的主题导致了人类植入前发育的低效率。
据了解,约50%的受精卵在人类着床前发育过程中停滞,这是辅助生殖技术的主要瓶颈。根本原因仍然存在争议。
附:英文原文
Title: Two distinct causes contribute to the low efficiency of human pre-implantation development
Author: Zixuan Li, Lizhi Leng, Jinglei Zhai, Xiaowen Wang, Wuling Yang, Shuhui Wang, Haifeng Wan, Shuoping Zhang, Fei Gong, Xi Liao, Yuhui Li, Qing Zeng, Yansu Chen, Zhenyu Xiang, Feiyao Liu, Fuchu He, Yun Yang, Hongmei Wang, Xiaoming Xu, Ge Lin, Chun So
Issue&Volume: 2026-06-11
Abstract: ~50% of fertilized eggs arrest during human pre-implantation development, representing a major bottleneck for assisted reproductive technology. The underlying causes remain controversial. By imaging ~150 live human and monkey fertilized eggs for up to 5 days, we uncovered that the second mitotic divisions are the most error-prone, accounting for early embryonic arrest. Stochastic centriole overduplication, which could be effectively suppressed by transient treatment with PLK4 inhibitor centrinone, predisposed 2-cell blastomeres to assembling multipolar spindles and missegregating chromosomes. Missegregated chromosomes in turn resulted in the formation of most micronuclei in human embryos and led to the arrest or death of daughter blastomeres. By contrast, late embryonic arrest was largely independent of chromosome missegregations but involved the activation of endoplasmic reticulum stress response, which could impair the expression of subsets of junctional and cell polarity proteins required for blastocyst formation. Thus, two distinct causes contribute to the low efficiency of human pre-implantation development.
DOI: 10.1016/j.cell.2026.05.037
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00637-9
期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:66.85
官方网址:https://www.cell.com/
投稿链接:https://www.editorialmanager.com/cell/default.aspx