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胚胎多核:检测、可能的起源及对治疗的影响。

Embryo multinucleation: detection, possible origins, and implications for treatment.

机构信息

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

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

出版信息

Hum Reprod. 2024 Nov 1;39(11):2392-2399. doi: 10.1093/humrep/deae186.

DOI:10.1093/humrep/deae186
PMID:39173609
Abstract

Cell cycle regulation is crucial to assure expansion of a cell population, while preserving genome integrity. This notion is especially relevant to fertilization and early embryo development, a time when the cell cycle transforms from meiotic into mitotic cycles. Zygote-to-embryo transition is acutely error-prone, causing major developmental perturbations, including cleavage delays, tri- and multi-chotomous cleavages, and cell fragmentation. Another such alteration is bi- and multinucleation, consisting of the simultaneous formation of two or more nuclei at interphase. Indeed, multinucleation affects a large proportion of early human embryos, typically at the two-cell stage. Mechanistically, several factors, including spindle dysfunction, failed cleavage, and cell fusion, may generate this cell anomaly. In assisted reproduction treatment, multinucleation is associated with reduced developmental rates and lower implantation rates in Days 2-3 embryo transfers. However, many multinucleated embryos can develop to the blastocyst stage. In blastocyst transfers, the current evidence does not suggest a major impact of a previous history of multinucleation on the odds of euploidy or successful treatment outcomes. Human embryo multinucleation remains a not-fully-understood but developmentally relevant and intriguing phenomenon which requires further research of its generative mechanisms and clinical implications.

摘要

细胞周期调控对于确保细胞群体的扩增和基因组完整性至关重要。这一概念在受精和早期胚胎发育中尤为重要,因为此时细胞周期从减数分裂转变为有丝分裂。从受精卵到胚胎的过渡非常容易出错,导致主要的发育紊乱,包括卵裂延迟、三裂和多裂以及细胞碎片化。另一种这样的改变是双核和多核化,包括在有丝分裂间期同时形成两个或更多核。事实上,多核化影响了很大一部分早期人类胚胎,通常在两细胞阶段。从机制上讲,纺锤体功能障碍、分裂失败和细胞融合等多种因素都可能导致这种细胞异常。在辅助生殖治疗中,多核化与胚胎发育率降低和第 2-3 天胚胎移植的着床率降低有关。然而,许多多核胚胎可以发育到囊胚阶段。在囊胚移植中,目前的证据表明,以前的多核化历史对整倍体的可能性或成功治疗结果没有重大影响。人类胚胎多核化仍然是一个尚未完全理解但与发育相关且引人入胜的现象,需要进一步研究其产生机制和临床意义。

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1
Embryo multinucleation: detection, possible origins, and implications for treatment.胚胎多核:检测、可能的起源及对治疗的影响。
Hum Reprod. 2024 Nov 1;39(11):2392-2399. doi: 10.1093/humrep/deae186.
2
Binucleated embryos at the two-cell stage show higher blastocyst formation rates and higher pregnancy and live birth rates compared to non-multinucleated embryos.与非多核胚胎相比,二细胞期的双核胚胎显示出更高的囊胚形成率、更高的妊娠率和活产率。
Hum Reprod Open. 2022 Nov 24;2022(4):hoac049. doi: 10.1093/hropen/hoac049. eCollection 2022.
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Impact of multinucleated blastomeres on embryo developmental competence, morphokinetics, and aneuploidy.多核胚胎碎片对胚胎发育能力、形态动力学和非整倍体的影响。
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Frequency of embryo multinucleation detected by time-lapse system and its impact on pregnancy outcome.时间延迟系统检测胚胎多核的频率及其对妊娠结局的影响。
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Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome.直接不等卵裂:胚胎发育能力、遗传构成与临床结局
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Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts.标准囊胚形态、整倍体与着床的相关性:两个中心涉及 956 枚筛选囊胚的观察性研究。
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Multinucleation in normally fertilized embryos is associated with an accelerated ovulation induction response and lower implantation and pregnancy rates in in vitro fertilization-embryo transfer cycles.正常受精胚胎中的多核化与体外受精-胚胎移植周期中促排卵反应加速以及着床率和妊娠率降低有关。
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Perturbations of morphogenesis at the compaction stage affect blastocyst implantation and live birth rates.在致密化阶段,形态发生的扰动会影响囊胚着床和活产率。
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Micronuclei in 2-cell embryos show higher blastocyst formation rates on human embryonic development.2 细胞胚胎中的微核显示出更高的囊胚形成率,有利于人类胚胎发育。
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Are cleavage anomalies, multinucleation, or specific cell cycle kinetics observed with time-lapse imaging predictive of embryo developmental capacity or ploidy?在延时成像中观察到的卵裂异常、多核或特定细胞周期动力学是否可预测胚胎发育能力或倍性?
Fertil Steril. 2018 Apr;109(4):665-674. doi: 10.1016/j.fertnstert.2017.12.025. Epub 2018 Feb 13.

引用本文的文献

1
Nuclear error phenotypes in the two-cell embryo are correlated to blastocyst formation rate after assisted reproduction.二细胞胚胎中的核异常表型与辅助生殖后的囊胚形成率相关。
J Assist Reprod Genet. 2025 Jan;42(1):115-124. doi: 10.1007/s10815-024-03354-9. Epub 2024 Dec 27.
2
Tackling multinucleation: a call for automated detection in time-lapse embryo monitoring.应对多核化:呼吁在延时胚胎监测中进行自动检测。
J Assist Reprod Genet. 2025 Jan;42(1):345-346. doi: 10.1007/s10815-024-03347-8. Epub 2024 Dec 13.