Sperm induction of somatic cell-cell fusion as a novel functional test
- Technion-Israel Institute of Technology, Israel
Abstract
The fusion of mammalian gametes requires the interaction between IZUMO1 on the sperm and JUNO on the oocyte. We have recently shown that ectopic expression of mouse IZUMO1 induces cell-cell fusion and that sperm can fuse to fibroblasts expressing JUNO. Here, we found that the incubation of mouse sperm with hamster fibroblasts or human epithelial cells in culture induces the fusion between these somatic cells and formation of syncytia, a pattern previously observed with some animal viruses. This sperm-induced cell-cell fusion requires a species-matching JUNO on both fusing cells, can be blocked by an antibody against IZUMO1, and does not rely on the synthesis of new proteins. The fusion is dependent on the sperm's fusogenic capacity, making this a reliable, fast and simple method for predicting sperm function during the diagnosis of male infertility.
Data availability
In all figures individual data is plotted. The raw data for the correlation analysis is found in Supplementary file 1.
Article and author information
Author details
Benjamin Podbilewicz
Funding
Israel Science Foundation (257/17)
- Benjamin Podbilewicz
Israel Science Foundation (2462/18)
- Benjamin Podbilewicz
Israel Science Foundation (2327/19)
- Benjamin Podbilewicz
Israel Science Foundation (178/20)
- Benjamin Podbilewicz
Horizon 2020 Framework Programme (844807)
- Nicolas G Brukman
Direccion General de Asuntos del Personal Academico, Programa de Estancias de Investigacion , UNAM
- Benjamin Podbilewicz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal studies were approved by the Committee on theEthics of Animal Experiments of the Technion - Israel Instituteof Technology.
Copyright
© 2024, Brukman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Sperm induction of somatic cell-cell fusion as a novel functional test
eLife 13:e94228.
https://doi.org/10.7554/eLife.94228
Further reading
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During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 activate the pluripotency-related genes through the putative OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory toward the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.
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