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.

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http://dx.doi.org/10.1038/s41598-017-04602-yDOI Listing

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