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受精最后阶段的延迟与三分体胞质分裂和卵裂停滞密切相关。

Delays in the final stages of fertilization are strongly associated with trichotomous cytokinesis and cleavage arrest.

作者信息

Coticchio Giovanni, Marchio Lorena, Bartolacci Alessandro, Cimadomo Danilo, Zacà Carlotta, Lagalla Cristina, Tarozzi Nicoletta, Borini Andrea, Rienzi Laura

机构信息

IVIRMA Global Research Alliance, IVIRMA ITALIA, Rome, Italy.

IVIRMA Global Research Alliance, 9.Baby, Bologna, Italy.

出版信息

J Assist Reprod Genet. 2025 Jan;42(1):107-114. doi: 10.1007/s10815-024-03330-3. Epub 2024 Nov 28.

DOI:10.1007/s10815-024-03330-3
PMID:39607653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11806123/
Abstract

PURPOSE

Recent evidence showed that the phase between pronuclear fading and the first cleavage is a perilous bridge connecting the zygote and the embryo. Indeed, delay in the short interval between pronuclear breakdown (PNBD) and the first cytokinesis may result in chromosome segregation errors. We tested the hypothesis that delays in this final phase of fertilization are associated with a detrimental impact on embryo development.

METHODS

This is a retrospective study of 1315 zygotes cultured using time lapse technologies generated in 205 first ICSI-cycles.

RESULTS

We observed an association between increasing times of the pronuclear fading-first cleavage interval (t2-tPNf) and the rates of trichotomous/direct unequal cleavage at the first (DUC-1) and second (DUC-2) mitotic cycle. Moreover, we observed a reduced blastulation rate. No significant associations were observed between rates of direct unequal cleavage at the third mitotic cycle (DUC-3) and top-quality blastocysts, euploidy, and live births. To evaluate whether the interval t2-tPNf could have a predictive value for the onset of DUC-1 and DUC-2, ROC curve analyses were performed. The area under the curve values obtained for DUC-1 showed a significant prediction accuracy. The best cut-offs to identify zygotes with a high risk of DUC-1 and DUC-2 occurrence were t2-tPNf > 2.78 (hours) and t2-tPNf > 2.50 (hours), respectively.

CONCLUSION

Delay in the short interval between PNBD and the first cytokinesis result in trichotomous cleavage and early developmental arrest. However, if the embryos reach the blastocyst stage, rates of euploidy and live birth do not appear to be compromised.

摘要

目的

最近有证据表明,原核消失与第一次卵裂之间的阶段是连接受精卵和胚胎的危险桥梁。事实上,原核破裂(PNBD)和第一次胞质分裂之间的短暂间隔延迟可能会导致染色体分离错误。我们检验了这样一个假设,即受精这个最后阶段的延迟会对胚胎发育产生不利影响。

方法

这是一项回顾性研究,研究对象为在205个首次卵胞浆内单精子注射(ICSI)周期中使用延时技术培养的1315个受精卵。

结果

我们观察到原核消失至第一次卵裂间隔时间(t2 - tPNf)延长与第一次(DUC - 1)和第二次(DUC - 2)有丝分裂周期的三分体/直接不等卵裂率之间存在关联。此外,我们还观察到囊胚形成率降低。在第三次有丝分裂周期的直接不等卵裂率(DUC - 3)与优质囊胚、整倍体及活产率之间未观察到显著关联。为了评估间隔时间t2 - tPNf是否对DUC - 1和DUC - 2的发生具有预测价值,我们进行了ROC曲线分析。DUC - 1所获得的曲线下面积值显示出显著的预测准确性。识别发生DUC - 1和DUC - 2高风险受精卵的最佳临界值分别为t2 - tPNf > 2.78(小时)和t2 - tPNf > 2.50(小时)。

结论

PNBD和第一次胞质分裂之间的短暂间隔延迟会导致三分体卵裂和早期发育停滞。然而,如果胚胎发育到囊胚阶段,整倍体率和活产率似乎并未受到影响。

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Meiotic and mitotic aneuploidies drive arrest of in vitro fertilized human preimplantation embryos.减数分裂和有丝分裂的非整倍性导致体外受精的人类胚胎停滞。
Genome Med. 2023 Oct 2;15(1):77. doi: 10.1186/s13073-023-01231-1.
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Cleavage Patterns of 9600 Embryos: The Importance of Irregular Cleavage.9600个胚胎的分裂模式:不规则分裂的重要性
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The first mitotic division of human embryos is highly error prone.人类胚胎的第一次有丝分裂高度易错。
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