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合子纺锤体方向决定了人类胚胎的卵裂模式和核状态。

Zygotic spindle orientation defines cleavage pattern and nuclear status of human embryos.

机构信息

Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Reprofit International, Clinic of Reproductive Medicine, Brno, Czech Republic.

出版信息

Nat Commun. 2024 Jul 29;15(1):6369. doi: 10.1038/s41467-024-50732-z.

DOI:10.1038/s41467-024-50732-z
PMID:39075061
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11286845/
Abstract

The first embryonic division represents a starting point for the development of a new individual. In many species, tight control over the first embryonic division ensures its accuracy. However, the first division in humans is often erroneous and can impair embryo development. To delineate the spatiotemporal organization of the first mitotic division typical for normal human embryo development, we systematically analyzed a unique timelapse dataset of 300 IVF embryos that developed into healthy newborns. The zygotic division pattern of these best-quality embryos was compared to their siblings that failed to implant or arrested during cleavage stage. We show that division at the right angle to the juxtaposed pronuclei is preferential and supports faithful zygotic division. Alternative configurations of the first mitosis are associated with reduced clustering of nucleoli and multinucleation at the 2-cell stage, which are more common in women of advanced age. Collectively, these data imply that orientation of the first division predisposes human embryos to genetic (in)stability and may contribute to aneuploidy and age-related infertility.

摘要

第一次卵裂代表着新个体发育的起点。在许多物种中,对第一次卵裂的严格控制确保了其准确性。然而,人类的第一次分裂往往是错误的,会损害胚胎的发育。为了描绘正常人类胚胎发育中第一次有丝分裂的时空组织,我们系统地分析了 300 个体外受精胚胎的独特延时数据集,这些胚胎发育成了健康的新生儿。将这些最佳质量胚胎的卵裂模式与未能着床或在卵裂期停滞的胚胎进行比较。我们发现,与毗邻原核成直角的分裂是首选的,并且支持合子的准确分裂。第一次有丝分裂的替代构型与核仁聚集减少和 2 细胞期的多核化有关,这些在高龄妇女中更为常见。总的来说,这些数据表明第一次分裂的方向使人类胚胎容易发生遗传(不)稳定性,并可能导致非整倍体和与年龄相关的不孕。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/18032235328c/41467_2024_50732_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/ebc7482be531/41467_2024_50732_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/3233cb0954a9/41467_2024_50732_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/846c015ae335/41467_2024_50732_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/198fbcb0232c/41467_2024_50732_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/18032235328c/41467_2024_50732_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/ebc7482be531/41467_2024_50732_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/3233cb0954a9/41467_2024_50732_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/846c015ae335/41467_2024_50732_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/198fbcb0232c/41467_2024_50732_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3054/11286845/18032235328c/41467_2024_50732_Fig5_HTML.jpg

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本文引用的文献

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Nat Commun. 2024 Jun 25;15(1):5381. doi: 10.1038/s41467-024-49815-8.
2
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.
3
The migration speed of nucleolar precursor bodies in pronuclei affects in vitro fertilization-derived human embryo ploidy status and live birth.
果蝇核孔蛋白ELYS在受精时对亲代染色体排列是必需的。
G3 (Bethesda). 2025 Jul 9;15(7). doi: 10.1093/g3journal/jkaf104.
4
On the origin of mitosis-derived human embryo aneuploidy.关于有丝分裂衍生的人类胚胎非整倍体的起源。
Nat Commun. 2024 Nov 29;15(1):10391. doi: 10.1038/s41467-024-54953-0.
原核中核仁前体的迁移速度影响体外受精衍生的人类胚胎倍性状态和活产。
Reprod Med Biol. 2023 Jan 20;22(1):e12497. doi: 10.1002/rmb2.12497. eCollection 2023 Jan-Dec.
4
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。
Nat Commun. 2022 Nov 8;13(1):6755. doi: 10.1038/s41467-022-34294-6.
5
Fertilization signatures as biomarkers of embryo quality.受精特征可作为胚胎质量的生物标志物。
Hum Reprod. 2022 Jul 30;37(8):1704-1711. doi: 10.1093/humrep/deac123.
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Parental genome unification is highly error-prone in mammalian embryos.父本和母本基因组的统一在哺乳动物胚胎中极易出错。
Cell. 2021 May 27;184(11):2860-2877.e22. doi: 10.1016/j.cell.2021.04.013. Epub 2021 May 7.
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Origins and mechanisms leading to aneuploidy in human eggs.人类卵子非整倍体形成的原因和机制。
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