Preimplantation chromosomal mosaics, chimaeras and confined placental mosaicism.

John D West, Clare A Everett
{"title":"Preimplantation chromosomal mosaics, chimaeras and confined placental mosaicism.","authors":"John D West,&nbsp;Clare A Everett","doi":"10.1530/RAF-21-0095","DOIUrl":null,"url":null,"abstract":"<p><p>Some human preimplantation embryos are chromosomally mosaic. For technical reasons, estimates of the overall frequency vary widely from <15 to >90% and the true frequency remains unknown. Aneuploid/diploid and aneuploid/aneuploid mosaics typically arise during early cleavage stages before the embryonic genome is fully activated and when cell cycle checkpoints are not operating normally. Other mosaics include chaotic aneuploid mosaics and mixoploids, some of which arise by abnormal chromosome segregation at the first cleavage division. Chimaeras are similar to mosaics, in having two genetically distinct cell populations, but they arise from more than one zygote and occur less often. After implantation, the frequency of mosaic embryos declines to about 2% and most are trisomic/diploid mosaics, with trisomic cells confined to the placenta. Thus, few babies are born with chromosomal mosaicism. This review discusses the origin of different types of chromosomal mosaics and chimaeras; their fate and the relationship between preimplantation chromosomal mosaicism and confined placental mosaicism in human conceptuses and animal models. Abnormal cells in mosaic embryos may be depleted by cell death, other types of cell selection or cell correction but the most severely affected mosaic embryos probably die. Trisomic cells could become restricted to placental lineages if cell selection or correction is less effective in placental lineages and/or they are preferentially allocated to a placental lineage. However, the relationship between preimplantation mosaicism and confined placental mosaicism may be complex because the specific chromosome(s) involved will influence whether chromosomally abnormal cells survive predominately in the placental trophoblast and/or placental mesenchyme.</p><p><strong>Lay summary: </strong>Human cells normally have 23 pairs of chromosomes, which carry the genes. During the first few days of development, some human embryos are chromosomal mosaics. These mosaic embryos have both normal cells and cells with an abnormal number of chromosomes, which arise from the same fertilised egg. (More rarely, the different cell populations arise from more than one fertilised egg and these embryos are called chimaeras.) If chromosomally abnormal cells survive to term, they could cause birth defects. However, few abnormal cells survive and those that do are usually confined to the placenta, where they are less likely to cause harm. It is not yet understood how this restriction occurs but the type of chromosomal abnormality influences which placental tissues are affected. This review discusses the origin of different types of chromosomally abnormal cells, their fate and how they might become confined to the placenta in humans and animal models.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066951/pdf/","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproduction & Fertility","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1530/RAF-21-0095","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3

Abstract

Some human preimplantation embryos are chromosomally mosaic. For technical reasons, estimates of the overall frequency vary widely from <15 to >90% and the true frequency remains unknown. Aneuploid/diploid and aneuploid/aneuploid mosaics typically arise during early cleavage stages before the embryonic genome is fully activated and when cell cycle checkpoints are not operating normally. Other mosaics include chaotic aneuploid mosaics and mixoploids, some of which arise by abnormal chromosome segregation at the first cleavage division. Chimaeras are similar to mosaics, in having two genetically distinct cell populations, but they arise from more than one zygote and occur less often. After implantation, the frequency of mosaic embryos declines to about 2% and most are trisomic/diploid mosaics, with trisomic cells confined to the placenta. Thus, few babies are born with chromosomal mosaicism. This review discusses the origin of different types of chromosomal mosaics and chimaeras; their fate and the relationship between preimplantation chromosomal mosaicism and confined placental mosaicism in human conceptuses and animal models. Abnormal cells in mosaic embryos may be depleted by cell death, other types of cell selection or cell correction but the most severely affected mosaic embryos probably die. Trisomic cells could become restricted to placental lineages if cell selection or correction is less effective in placental lineages and/or they are preferentially allocated to a placental lineage. However, the relationship between preimplantation mosaicism and confined placental mosaicism may be complex because the specific chromosome(s) involved will influence whether chromosomally abnormal cells survive predominately in the placental trophoblast and/or placental mesenchyme.

Lay summary: Human cells normally have 23 pairs of chromosomes, which carry the genes. During the first few days of development, some human embryos are chromosomal mosaics. These mosaic embryos have both normal cells and cells with an abnormal number of chromosomes, which arise from the same fertilised egg. (More rarely, the different cell populations arise from more than one fertilised egg and these embryos are called chimaeras.) If chromosomally abnormal cells survive to term, they could cause birth defects. However, few abnormal cells survive and those that do are usually confined to the placenta, where they are less likely to cause harm. It is not yet understood how this restriction occurs but the type of chromosomal abnormality influences which placental tissues are affected. This review discusses the origin of different types of chromosomally abnormal cells, their fate and how they might become confined to the placenta in humans and animal models.

Abstract Image

Abstract Image

Abstract Image

着床前染色体嵌合体、嵌合体和受限胎盘嵌合体。
一些人类胚胎植入前是染色体嵌合的。由于技术原因,对总体频率的估计相差很大,从90%到真实频率仍然未知。非整倍体/二倍体和非整倍体/非整倍体嵌合通常发生在胚胎基因组完全激活之前的早期卵裂阶段,当细胞周期检查点不正常工作时。其他嵌合体包括混乱的非整倍体嵌合体和混合倍体,其中一些是由第一次卵裂分裂时染色体异常分离引起的。嵌合体类似于嵌合体,具有两个基因不同的细胞群,但它们产生于多个受精卵,发生的频率较低。植入后,嵌合体胚胎的发生率下降到2%左右,大多数是三体/二倍体嵌合体,三体细胞局限于胎盘。因此,很少有婴儿出生时带有染色体镶嵌现象。本文综述了不同类型染色体嵌合体和嵌合体的起源;它们的命运以及着床前染色体嵌合与受限胎盘嵌合在人类和动物模型中的关系。嵌合胚胎中的异常细胞可能因细胞死亡、其他类型的细胞选择或细胞校正而耗尽,但受影响最严重的嵌合胚胎可能死亡。如果在胎盘谱系中细胞选择或校正效果较差和/或它们被优先分配到胎盘谱系中,三体细胞可能被限制在胎盘谱系中。然而,着床前嵌合和受限胎盘嵌合之间的关系可能是复杂的,因为所涉及的特定染色体将影响染色体异常细胞是否主要存活于胎盘滋养细胞和/或胎盘间质中。人类细胞通常有23对携带基因的染色体。在发育的最初几天,一些人类胚胎是染色体嵌合体。这些镶嵌胚胎既有正常细胞,也有染色体数量异常的细胞,它们都来自同一个受精卵。(更罕见的是,不同的细胞群来自不止一个受精卵,这些胚胎被称为嵌合体。)如果染色体异常细胞存活到足月,它们可能会导致出生缺陷。然而,很少有异常细胞存活下来,而那些存活下来的细胞通常被限制在胎盘中,在那里它们不太可能造成伤害。目前尚不清楚这种限制是如何发生的,但染色体异常的类型会影响胎盘组织。这篇综述讨论了不同类型染色体异常细胞的起源,它们的命运以及它们如何在人类和动物模型中被限制在胎盘中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信