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Publication : Knockdown of Toe1 causes developmental arrest during the morula-to-blastocyst transition in mice.

First Author  Wang H Year  2022
Journal  Theriogenology Volume  194
Pages  154-161 PubMed ID  36257135
Mgi Jnum  J:332468 Mgi Id  MGI:7425469
Doi  10.1016/j.theriogenology.2022.10.011 Citation  Wang H, et al. (2022) Knockdown of Toe1 causes developmental arrest during the morula-to-blastocyst transition in mice. Theriogenology 194:154-161
abstractText  The target of EGR1 protein 1 (TOE1) is evolutionarily conserved from Caenorhabditis elegans to mammals, which plays a critical role in the maturation of a variety of small nuclear RNAs. Mutation in human TOE1 has been reported to cause pontocerebellar hypoplasia type 7, a severe neurodegenerative syndrome. However, the role of TOE1 in early embryonic development remains unclear. Herein, we found that Toe1 mRNA and protein were expressed in mouse preimplantation embryos. Silencing Toe1 by siRNA led to morula-to-blastocyst transition failure. This developmental arrest can be rescued by Toe1 mRNA microinjection. EdU incorporation assay showed a defect in blastomere proliferation within developmentally arrested embryos. Further studies revealed that Toe1 knockdown caused increased signals for gammaH2AX and micronuclei, indicative of sustained DNA damage. Moreover, mRNA levels of cell cycle inhibitor p21 were significantly upregulated in Toe1 knockdown embryos before developmental arrest. Together, these results suggest that TOE1 is indispensable for mouse early embryo development potentially through maintaining genomic integrity. Our findings provide further insight into the role of TOE1 in mouse preimplantation embryonic development.
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