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Published on: December 16, 2016
The interferon α-responsive gene, Ifrg15, plays vital roles during mouse early embryonic development
Ye Yang1, Jiayi Wang1, Chun Zhao1
1State Key Laboratory of Reproductive Medicine, Department of Reproduction, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing Medical University, Nanjing, 210004, Jiangsu, China.
Abstract:
The interferon alpha-responsive gene (Ifrg15) mRNA is highly expressed in various stages during preimplantation mammalian embryo development. Unfortunately, few studies have investigated the effect of Ifrg15 in this process. In mammals, the fusion of male and female pronuclei generates a diploid zygote, and is an important step for subsequent cleavage and blastocyst formation. Here, by using RNA interference, rescue experiments, immunofluorescence staining and live cell observations, we found that preimplantation embryo development was arrested at the 1-cell stage after knocking down Ifrg15 expression. This induced DNA damage and prevented the cleavage of embryos. Furthermore, the effect of Ifrg15 deficiency in arresting preimplantation embryo development produced by specific short interfering RNA microinjection was concentration-dependent. Using transcriptome expression profiles, gene ontogeny functional annotation and enrichment analysis, we gained 197 enriched pathways based on 1445 differentially expressed genes (DEGs). Of these, 12 pathways and about one third of the DEGs were involved in DNA damage, DNA repair, cell cycle, and developmental processes. Thus, the IFRG15 protein might be an important molecule for maintaining genomic integrity and stability through upregulating or downregulating a cascade of genes to permit normal preimplantation embryo development.
Insights
Interferon alpha-responsive gene 15 (Ifrg15) is crucial for early mammalian embryo development. Knocking down Ifrg15 arrests development, causing DNA damage and preventing cell division.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Interferon alpha-responsive gene 15 (Ifrg15) mRNA is highly expressed during preimplantation mammalian embryo development.
- Its specific role in early embryogenesis remains largely unexplored.
- Proper pronuclear fusion and subsequent development are critical for mammalian reproduction.
Purpose of the Study:
- To investigate the function of Ifrg15 during preimplantation mammalian embryo development.
- To determine the molecular mechanisms underlying Ifrg15's role in early embryonic stages.
Main Methods:
- RNA interference (RNAi) for gene knockdown.
- Rescue experiments to validate findings.
- Immunofluorescence staining and live cell imaging.
- Transcriptome analysis (RNA sequencing) and bioinformatics.
Main Results:
- Knockdown of Ifrg15 expression led to developmental arrest at the 1-cell stage in mammalian embryos.
- Ifrg15 deficiency induced significant DNA damage and inhibited embryo cleavage.
- The observed effects were concentration-dependent on the short interfering RNA used.
- Transcriptome analysis revealed 1445 differentially expressed genes and 197 enriched pathways, with many related to DNA damage, repair, and cell cycle regulation.
Conclusions:
- The IFRG15 protein is essential for maintaining genomic integrity and stability during preimplantation development.
- IFRG15 regulates a cascade of genes involved in DNA repair and cell cycle control.
- These regulatory functions are vital for successful mammalian embryo development.
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