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[胎盘发育与内源性逆转录病毒]

[Placental Development and Endogenous Retroviruses].

作者信息

Imakawa Kazuhiko, Nakagawa So, Kusama Kazuya

机构信息

Animal Resource Science Center, The University of Tokyo.

Department of Molecular Life Science, Tokai University School of Medicine.

出版信息

Uirusu. 2016;66(1):1-10. doi: 10.2222/jsv.66.1.

Abstract

A placenta as we know now is a relatively new invention in mammals. Data accumulated indicates that a major cell type of the placenta is trophoblast, in which elevated expression of genes derived from various endogenous retroviruses (ERVs) as well as LTR retrotransposons is seen. However, evolutionally significance of ERV expression in placental development has not been well characterized or sorted out. In this review, we describe diversity of placental structures among mammalian species, of which morphological and cells types are far more diverse than those expected from the lines of mammalian orders. We then describe paternally expressed gene 10 (Peg10/Sirh1) and Peg11/Sirh2 as ERVs associated with ancient placenta development, followed by env-related genes such as Syncytin-1, -2, -A, -B, -Rum1, and Fematrin-1 responsible for trophoblast cells fusion, resulting in multinucleate syncytiotrophoblast formation. Because the endogenization of retroviral infections has occurred multiple times in different mammalian lineages, and some of them use similar molecules in their transcriptional activation, we speculate that ERV gene variants integrated into mammalian genomes in a locus specific manner have replaced the genes previously responsible for cell fusion. The role of cell fusion achieved by multiple successive ERV integrations is now called ''baton pass'' hypothesis, possibly resulting in increased trophoblast cell fusion, morphological diversity in placental structures, and survivability of fetuses and/or reproductive advantage in placental mammals.

摘要

我们现在知道,胎盘是哺乳动物中一项相对较新的发明。积累的数据表明,胎盘的主要细胞类型是滋养层细胞,在这种细胞中可以看到源自各种内源性逆转录病毒(ERV)以及LTR逆转座子的基因表达升高。然而,ERV表达在胎盘发育中的进化意义尚未得到很好的表征或梳理。在这篇综述中,我们描述了哺乳动物物种间胎盘结构的多样性,其形态和细胞类型远比从哺乳动物目系中预期的要多样得多。然后我们描述了与古老胎盘发育相关的父系表达基因10(Peg10/Sirh1)和Peg11/Sirh2,接着是与env相关的基因,如Syncytin-1、-2、-A、-B、-Rum1和Fematrin-1,它们负责滋养层细胞融合,从而形成多核合体滋养层细胞。由于逆转录病毒感染的内源性化在不同的哺乳动物谱系中多次发生,并且其中一些在转录激活中使用相似的分子,我们推测以位点特异性方式整合到哺乳动物基因组中的ERV基因变体已经取代了先前负责细胞融合的基因。通过多次连续的ERV整合实现的细胞融合作用现在被称为“接力棒传递”假说,这可能导致滋养层细胞融合增加、胎盘结构的形态多样性以及胎盘哺乳动物胎儿的生存能力和/或生殖优势。

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