Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis

Abstract A diploid genome is necessary for normal mammalian development, thus haploid parthenogenetic embryos undergo frequent self-diploidization during preimplantation development; however, the underlying mechanism is unclear. In this study, time-lapse recording revealed that human haploid parthen...

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Autores principales:	Lizhi Leng, Qi Ouyang, Xiangyi Kong, Fei Gong, Changfu Lu, Lei Zhao, Yun Shi, Dehua Cheng, Liang Hu, Guangxiu Lu, Ge Lin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5826ef19c1a149c3ae1cc997ed119aef
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spelling	oai:doaj.org-article:5826ef19c1a149c3ae1cc997ed119aef2021-12-02T11:53:03ZSelf-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis10.1038/s41598-017-04602-y2045-2322https://doaj.org/article/5826ef19c1a149c3ae1cc997ed119aef2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04602-yhttps://doaj.org/toc/2045-2322Abstract A diploid genome is necessary for normal mammalian development, thus haploid parthenogenetic embryos undergo frequent self-diploidization during preimplantation development; however, the underlying mechanism is unclear. In this study, time-lapse recording revealed that human haploid parthenotes (HPs) undergo self-diploidization via failed cytokinesis (FC) and endomitosis (EM). The frequencies of FC/EM were significantly higher in HPs than in normal fertilized embryos (26.3% vs. 1.6%, P < 0.01; 19.7% vs. 0, P < 0.01), and above 90% of FC/EM occurred at the first cell cycle in HPs. Fluorescent in situ hybridization of chromosome 16,18 and X in HPs identified diploid recovery after the appearance of FC/EM, and FC/EM HPs showed improved blastocyst formation compared with non-FC/EM HPs (18.8% and 40.0% vs. 15.4%, P > 0.05). In 66.7% of the 1-cell stage HPs, furrow ingression was not observed during the time for normal cleavage, and both immunostaining and gene expression analysis of 1-cell stage HPs revealed the absence or down-regulation of several key genes of the Rho pathway, which regulates cytomitosis. Our results suggested that the major mechanism for self-diploidization is Rho pathway inhibition leading to FC/EM in the first cell cycle, and fine-tuning of this signalling pathway may help to generate stable haploid embryos for stem cell biology studies.Lizhi LengQi OuyangXiangyi KongFei GongChangfu LuLei ZhaoYun ShiDehua ChengLiang HuGuangxiu LuGe LinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lizhi Leng Qi Ouyang Xiangyi Kong Fei Gong Changfu Lu Lei Zhao Yun Shi Dehua Cheng Liang Hu Guangxiu Lu Ge Lin Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis
description	Abstract A diploid genome is necessary for normal mammalian development, thus haploid parthenogenetic embryos undergo frequent self-diploidization during preimplantation development; however, the underlying mechanism is unclear. In this study, time-lapse recording revealed that human haploid parthenotes (HPs) undergo self-diploidization via failed cytokinesis (FC) and endomitosis (EM). The frequencies of FC/EM were significantly higher in HPs than in normal fertilized embryos (26.3% vs. 1.6%, P < 0.01; 19.7% vs. 0, P < 0.01), and above 90% of FC/EM occurred at the first cell cycle in HPs. Fluorescent in situ hybridization of chromosome 16,18 and X in HPs identified diploid recovery after the appearance of FC/EM, and FC/EM HPs showed improved blastocyst formation compared with non-FC/EM HPs (18.8% and 40.0% vs. 15.4%, P > 0.05). In 66.7% of the 1-cell stage HPs, furrow ingression was not observed during the time for normal cleavage, and both immunostaining and gene expression analysis of 1-cell stage HPs revealed the absence or down-regulation of several key genes of the Rho pathway, which regulates cytomitosis. Our results suggested that the major mechanism for self-diploidization is Rho pathway inhibition leading to FC/EM in the first cell cycle, and fine-tuning of this signalling pathway may help to generate stable haploid embryos for stem cell biology studies.
format	article
author	Lizhi Leng Qi Ouyang Xiangyi Kong Fei Gong Changfu Lu Lei Zhao Yun Shi Dehua Cheng Liang Hu Guangxiu Lu Ge Lin
author_facet	Lizhi Leng Qi Ouyang Xiangyi Kong Fei Gong Changfu Lu Lei Zhao Yun Shi Dehua Cheng Liang Hu Guangxiu Lu Ge Lin
author_sort	Lizhi Leng
title	Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis
title_short	Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis
title_full	Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis
title_fullStr	Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis
title_full_unstemmed	Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis
title_sort	self-diploidization of human haploid parthenogenetic embryos through the rho pathway regulates endomitosis and failed cytokinesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5826ef19c1a149c3ae1cc997ed119aef
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Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis

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