Potential Involvement of SCF-Complex in Zygotic Genome Activation During Early Bovine Embryo Development

Mitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inhibition of DRP1 activity by mitochondrial division inhibitor-1, a small molecule reported to specifically inhibit DRP1 activity, can cause severe developmental arrest of preimplantation embryos in a dose-dependent manner in mice. Meanwhile, DRP1 inhibition resulted in mitochondrial dysfunction including decreased mitochondrial activity, loss of mitochondrial membrane potential, reduced mitochondrial copy number and inadequate ATP by disrupting both expression and activity of DRP1 and mitochondrial complex assembly, leading to excessive ROS production, severe DNA damage and cell cycle arrest at 2-cell embryo stage. Furthermore, reduced transcriptional and translational activity and altered histone modifications in DRP1-inhibited embryos contributed to impeded zygotic genome activation, which prevented early embryos from efficient development beyond 2-cell embryo stage. These results show that DRP1 inhibition has potential cytotoxic effects on mammalian reproduction, and DRP1 inhibitor should be used with caution when it is applied to treat diseases. Additionally, this study improves our understanding of the crosstalk between mitochondrial metabolism and zygotic genome activation.

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Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development

Scientific Reports ◽

10.1038/s41598-019-44882-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Elo Madissoon ◽

Anastasios Damdimopoulos ◽

Shintaro Katayama ◽

Kaarel Krjutškov ◽

Elisabet Einarsdottir ◽

...

Keyword(s):

Pleomorphic Adenoma ◽

Embryo Development ◽

Early Embryo ◽

Zygotic Genome Activation ◽

Early Embryo Development ◽

Genome Activation ◽

Zygotic Genome

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190 SPINDLIN 1 IS REQUIRED FOR METAPHASE II ARREST IN PORCINE OOCYTES

Reproduction Fertility and Development ◽

10.1071/rdv28n2ab190 ◽

2016 ◽

Vol 28 (2) ◽

pp. 226

Author(s):

J.-W. Choi ◽

T. Kim ◽

N.-H. Kim ◽

X.-S. Cui

Keyword(s):

Embryo Development ◽

Oocyte Maturation ◽

Messenger Rna ◽

Fluorescent Protein ◽

Rrna Genes ◽

Control Group ◽

Rrna Gene ◽

Zygotic Genome Activation ◽

Genome Activation ◽

Zygotic Genome

Spindlin 1 (Spin1), is a histone methylation effecter protein. It can specifically recognise and bind to trimethylated histone 3 lysine 4 (H3K4). Spin1 localizes to the active rDNA repeats and facilitates the expressions of rRNA genes. For exploring the function of Spin1 in porcine oocyte and embryo development, siRNA of Spin1 (siSpin1) was used in the present study. Messenger RNA level of Spin1 was more highly expressed in the ovary than other tissues. During oocyte maturation, Spin1 was highly expressed from germinal vesicle to metaphase II stage in oocyes but sharply decreased after zygotic genome activation. The SPIN1 protein was localised to the cytoplasm and showed a similar expression pattern with mRNA through all stages of early embryonic development. Spin1 was successfully knocked down by siRNA injection. The siRNA of green fluorescent protein (siGFP) was used as positive control, and distilled water (DW) was used as a negative control. All were injected at metaphase II stage. Oocyte maturation was not altered by siSpin1 microinjection, but the rate of embryo development was significantly decreased from 4-cell stage when compared with the control group. The Spin1 had an effect on the blastocyst formation, which may have been altered by polymerase I-mediated rRNA gene transcription via regulation of H3K4 methylation. On the other hand, pronuclear formation was reduced by Spin1 siRNA. All data were analysed with a one-way analysis of variance, and differences between treatment groups were assessed by l.s.d. test, using SPSS software. In conclusion, Spin1 may be involved in metaphase arrest in oocyte and zygotic genome activation during early embryo development in pigs.

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Wenshen Shengjing Decoction Improves Early Embryo Development by Maintaining Low H3K27me3 Levels in Sperm and Pronuclear Embryos of Spermatogenesis Impaired Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8035997 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Yanmei Sun ◽

Fan Gao ◽

Da Xu ◽

Lei Lu ◽

Qianggen Chen ◽

...

Keyword(s):

Embryo Development ◽

Early Embryo ◽

Development Rate ◽

Epigenetic Changes ◽

Zygotic Genome Activation ◽

Arrest Rate ◽

Developmental Arrest ◽

Early Embryos ◽

Genome Activation ◽

Zygotic Genome

Many ingredients in Wenshen Shengjing Decoction (WSSJD) can cause epigenetic changes in the development of different types of cells. It is not yet known whether they can cause epigenetic changes in sperms or early embryos. Here, we investigated the role of WSSJD in epigenetic modifications of sperms or early embryos and early embryo development. A mouse model with spermatogenesis disorders was established with cyclophosphamide (CPA). WSSJD was administrated for 30 days. The male model mice after the treatment were mated with the female mice treated with superovulation. The embryo development rate of each stage was calculated. Immunofluorescence staining was used to detect the expression of H3K27me3 in sperm, pronuclear embryos, and 2-cell embryos. Western blotting was used to detect the expression of histone demethylase KDM6A and methyltransferase EZH2 in 2-cell embryos with developmental arrest. The expressions of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) in 2-cell embryos with developmental arrest were analyzed with qRT-PCR. Comparing with the control group, CPA destroyed the development of seminiferous epithelium, significantly increased the expression level of H3K27me3 in sperm, reduced the expression ratio of H3K27me3 in female and male pronuclei, delayed the development of 2-cell embryos, and increased the developmental arrest rate and degeneration rate of 2-cell embryos. Moreover, the expressions of EZH2 and H3K27me3 were significantly increased in the 2-cell embryos with developmental arrest, and the expression of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) was significantly decreased. Compared with the CPA group, WSSJD promoted the development of seminiferous epithelium, maintained a low level of H3K27me3 modification in sperm and male pronucleus, significantly increased the development rate of 2-cell embryos and 3-4 cell embryos, and reduced the developmental arrest rate and degeneration rate of 2-cell embryos. WSSJD may promote early embryonic development by maintaining a low level of H3K27me3 modification in sperm and male pronucleus and regulating the zygotic genome activation in mice with spermatogenesis disorders induced by CPA.

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Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development

10.1101/305375 ◽

2018 ◽

Author(s):

Elo Madissoon ◽

Anastasios Damdimopoulos ◽

Shintaro Katayama ◽

Kaarel Krjutškov ◽

Elisabet Einarsdottir ◽

...

Keyword(s):

Pleomorphic Adenoma ◽

Embryo Development ◽

Ribosome Biogenesis ◽

De Novo ◽

Paternal Allele ◽

Human Embryos ◽

Zygotic Genome Activation ◽

Dna Motif ◽

Genome Activation ◽

Zygotic Genome

ABSTRACTPleomorphic adenoma gene 1 (PLAG1) is a transcription factor involved in cancer and growth. We discovered a de novo DNA motif containing a PLAG1 binding site in the promoters of genes activated during zygotic genome activation (ZGA) in human embryos. This motif was located within an Alu element in a region that was conserved in the murine B1 element. We show that maternally provided Plag1 is essential for timely mouse preimplantation embryo development. Heterozygous mouse embryos lacking maternal Plag1 showed disrupted regulation of 1,089 genes, spent significantly longer time in the 2-cell stage, and started expressing Plag1 ectopically from the paternal allele. The de novo PLAG1 motif was enriched in the promoters of the genes whose activation was delayed in the absence of Plag1. Further, these mouse genes showed a significant overlap with genes upregulated during human ZGA that also contain the motif. By gene ontology, the mouse and human ZGA genes with de novo PLAG1 motifs were involved in ribosome biogenesis and protein synthesis. Collectively, our data suggest that PLAG1 affects embryo development in mice and humans through a conserved DNA motif within Alu/B1 elements located in the promoters of a subset of ZGA genes.

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