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Despite zygotic genome activation (ZGA) is crucial for early embryonic development, its regulatory mechanism is still unclear in mammals. In the present study, we demonstrate that TRPS1, a maternal factor, plays an essential role in mouse early embryogenesis by regulating the transition from 2-cell to 4-cell embryos during preimplantation development. The absence of Trps1 could leads to impaired ZGA through AKT/CREB signaling pathway. Furthermore, our findings suggest that TRPS1 may modulate the transcription of Pde4d to influence AKT and CREB phosphorylation. Interestingly, compared to Trps1 knockdown alone, co-injection of Trps1 siRNA and Pde4d mRNA significantly enhances the development rate of 4-cell embryos. Collectively, these results indicate a negative involvement of Trps1 in mouse preimplantation embryo development by targeting the PDE4D/AKT/CREB pathway to regulate ZGA.
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http://dx.doi.org/10.1007/s10565-025-09999-1 | DOI Listing |
PLoS One
September 2025
Division of Reproductive Engineering, Center for Animal Resources and Development, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
Zygotes are used to create genetically modified animals by electroporation using the CRISPR-Cas9 system. Such zygotes in rats are obtained from superovulated female rats after mating. Recently, we reported that in vivo-fertilized zygotes had higher cryotolerance and developmental ability than in vitro-fertilized zygotes in Sprague Dawley (SD) and Fischer 344 rats.
View Article and Find Full Text PDFEMBO Rep
September 2025
School of Biological and Behavioural Sciences, Queen Mary University of London, Mile End Road, E1 4NS, London, UK.
Early animal development can be remarkably variable, influenced by lineage-specific reproductive strategies and adaptations. Yet, early embryogenesis is also strikingly conserved in certain groups, such as Spiralia. In this clade, a shared cleavage program (i.
View Article and Find Full Text PDFDev Cell
August 2025
Friedrich Miescher Institute for Biomedical Research, 4056 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland. Electronic address:
Except for regulatory CpG-island sequences, genomes of most mammalian cells are widely DNA-methylated. In oocytes, though, DNA methylation (DNAme) is largely confined to transcribed regions. The mechanisms restricting de novo DNAme in oocytes and their relevance thereof for zygotic genome activation and embryonic development are largely unknown.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Federal Research Center Institute of Cytology and Genetics, Siberian Branch of RAS, Lavrentyeva 10, 630090 Novosibirsk, Russia.
Zygotic genome activation (ZGA) represents one of the most vulnerable periods to environmental perturbations. The objective of this study was to investigate the formation of stress granules in mouse embryos in response to temperature reduction during ZGA, preimplantation embryo mortality, and long-term phenotypic outcomes. These outcomes included the evaluation of expression noise in bilateral right/left limbs of offspring as an indicator of developmental instability, behavioral deviation, hippocampal volume, and metabolomics profiling in adult offspring.
View Article and Find Full Text PDFSkelet Muscle
August 2025
Randall Centre for Cell and Molecular Biophysics, King's College London, Guy's Campus, London, SE1 1UL, UK.
Double Homeobox 4 (DUX4) is a potent transcription factor encoded by a retrogene mapped in D4Z4 repeated elements on chromosome 4q35. DUX4 has emerged as pivotal in the pathomechanisms of facioscapulohumeral muscular dystrophy (FSHD), a relatively common hereditary muscle wasting condition, although classified as a rare disease. DUX4 contributes to zygote genome activation before its expression is repressed in most somatic tissues through epigenetic mechanisms, including DNA methylation and chromatin modifications.
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