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

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.

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

2019 ◽  
Vol 9 (1) ◽  
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

scholarly journals Single cell RNA-seq reveals genes vital to in vitro fertilized embryos and parthenotes in pigs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhi-Qiang Du ◽  
Hao Liang ◽  
Xiao-Man Liu ◽  
Yun-Hua Liu ◽  
Chonglong Wang ◽  
...  
Keyword(s):  
Embryo Development ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Expression Patterns ◽  
Early Embryo ◽  
Specific Factor ◽  
Early Embryos ◽  
Genome Activation

AbstractSuccessful early embryo development requires the correct reprogramming and configuration of gene networks by the timely and faithful execution of zygotic genome activation (ZGA). However, the regulatory principle of molecular elements and circuits fundamental to embryo development remains largely obscure. Here, we profiled the transcriptomes of single zygotes and blastomeres, obtained from in vitro fertilized (IVF) or parthenogenetically activated (PA) porcine early embryos (1- to 8-cell), focusing on the gene expression dynamics and regulatory networks associated with maternal-to-zygote transition (MZT) (mainly maternal RNA clearance and ZGA). We found that minor and major ZGAs occur at 1-cell and 4-cell stages for both IVF and PA embryos, respectively. Maternal RNAs gradually decay from 1- to 8-cell embryos. Top abundantly expressed genes (CDV3, PCNA, CDR1, YWHAE, DNMT1, IGF2BP3, ARMC1, BTG4, UHRF2 and gametocyte-specific factor 1-like) in both IVF and PA early embryos identified are of vital roles for embryo development. Differentially expressed genes within IVF groups are different from that within PA groups, indicating bi-parental and maternal-only embryos have specific sets of mRNAs distinctly decayed and activated. Pathways enriched from DEGs showed that RNA associated pathways (RNA binding, processing, transport and degradation) could be important. Moreover, mitochondrial RNAs are found to be actively transcribed, showing dynamic expression patterns, and for DNA/H3K4 methylation and transcription factors as well. Taken together, our findings provide an important resource to investigate further the epigenetic and genome regulation of MZT events in early embryos of pigs.

scholarly journals Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuanyuan Li ◽  
Ning-Hua Mei ◽  
Gui-Ping Cheng ◽  
Jing Yang ◽  
Li-Quan Zhou
Keyword(s):  
Embryo Development ◽  
Preimplantation Embryo ◽  
Preimplantation Embryos ◽  
Dependent Manner ◽  
Zygotic Genome Activation ◽  
Preimplantation Embryo Development ◽  
Cell Embryo ◽  
Embryo Stage ◽  
Genome Activation ◽  
Zygotic Genome

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.

scholarly journals The miR-430 locus with extreme promoter density is a transcription body organizer, which facilitates long range regulation in zygotic genome activation

2021 ◽  
Author(s):  
Yavor Hadzhiev ◽  
Lucy Wheatley ◽  
Ledean Cooper ◽  
Federico Ansaloni ◽  
Celina Whalley ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Gene Cluster ◽  
Core Promoter ◽  
Single Copy ◽  
Early Embryo ◽  
Zygotic Genome Activation ◽  
Pol Ii ◽  
A Minor ◽  
Genome Activation ◽  
Zygotic Genome

In anamniote embryos the major wave of zygotic genome activation (ZGA) starts during the mid-blastula transition. This major wave of ZGA is facilitated by several mechanisms, including dilution of repressive maternal factors and accumulation of activating transcription factors during the fast cell division cycles preceding the mid-blastula transition. However, a set of genes escape global genome repression and are activated substantially earlier, during what is called, the minor wave of genome activation. While the mechanisms underlying the major wave of genome activation have been studied extensively, the minor wave of genome activation is little understood. In zebrafish the earliest expressed RNA polymerase II (Pol II) transcribed genes are activated in a pair of large transcription bodies depleted of chromatin, abundant in elongating Pol II and nascent RNAs (Hadzhiev et al., 2019; Hilbert et al., 2021). This transcription body includes the miR-430 gene cluster required for maternal mRNA clearance. Here we explored the genomic, chromatin organisation and cis-regulatory mechanisms of the minor wave of genome activation occurring in the transcription body. By long read genome sequencing we identified a remarkable cluster of miR-430 genes with over 300 promoters and spanning 0.6 Mb, which represent the highest promoter density of the genome. We demonstrate that the miR-430 gene cluster is required for the formation of the transcription body and acts as a transcription organiser for minor wave activation of a set of zinc finger genes scattered on the same chromosome arm, which share promoter features with the miR-430 cluster. These promoter features are shared among minor wave genes overall and include the TATA-box and sharp transcription start site profile. Single copy miR-430 promoter transgene reporter experiments indicate the importance of promoter-autonomous mechanisms regulating escape from global repression of the early embryo. These results together suggest that formation of the transcription body in the early embryo is the result of high promoter density coupled to a minor wave-specific core promoter code for transcribing key minor wave ZGA genes, which are required for the overhaul of the transcriptome during early embryonic development.

scholarly journals Transcriptional Activation of Arabidopsis Zygotes Is Required for Initial Cell Divisions

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ping Kao ◽  
Michael D. Nodine
Keyword(s):  
Transcriptional Activation ◽  
Gene Products ◽  
Zygotic Genome Activation ◽  
Microscopy Technique ◽  
Early Embryos ◽  
Maternal To Zygotic Transition ◽  
Parental Gene ◽  
Active Transcription ◽  
Genome Activation ◽  
Zygotic Genome

AbstractCommonly referred to as the maternal-to-zygotic transition, the shift of developmental control from maternal-to-zygotic genomes is a key event during animal and plant embryogenesis. Together with the degradation of parental gene products, the increased transcriptional activities of the zygotic genome remodels the early embryonic transcriptome during this transition. Although evidence from multiple flowering plants suggests that zygotes become transcriptionally active soon after fertilization, the timing and developmental requirements of zygotic genome activation in Arabidopsis thaliana (Arabidopsis) remained a matter of debate until recently. In this report, we optimized an expansion microscopy technique for robust immunostaining of Arabidopsis ovules and seeds. This enabled the detection of marks indicative of active transcription in zygotes before the first cell division. Moreover, we employed a live-imaging culture system together with transcriptional inhibitors to demonstrate that such active transcription is physiologically required in zygotes and early embryos. Our results indicate that zygotic genome activation occurs soon after fertilization and is required for the initial zygotic divisions in Arabidopsis.

scholarly journals The miR-125 family is an important regulator of the expression and maintenance of maternal effect genes during preimplantational embryo development

Open Biology ◽  
2016 ◽  
Vol 6 (11) ◽  
pp. 160181 ◽  
Author(s):  
Kyeoung-Hwa Kim ◽  
You-Mi Seo ◽  
Eun-Young Kim ◽  
Su-Yeon Lee ◽  
Jini Kwon ◽  
...  
Keyword(s):  
Embryo Development ◽  
Maternal Effect ◽  
Early Embryo ◽  
Binding Motif ◽  
Seed Region ◽  
Maternal Effect Gene ◽  
Maternal Effect Genes ◽  
Important Regulator ◽  
Genome Activation ◽  
Zygotic Genome

Previously, we reported that Sebox is a new maternal effect gene (MEG) that is required for early embryo development beyond the two-cell (2C) stage because this gene orchestrates the expression of important genes for zygotic genome activation (ZGA). However, regulators of Sebox expression remain unknown. Therefore, the objectives of the present study were to use bioinformatics tools to identify such regulatory microRNAs (miRNAs) and to determine the effects of the identified miRNAs on Sebox expression. Using computational algorithms, we identified a motif within the 3′UTR of Sebox mRNA that is specific to the seed region of the miR-125 family, which includes miR-125a-5p, miR-125b-5p and miR-351-5p. During our search for miRNAs, we found that the Lin28a 3′UTR also contains the same binding motif for the seed region of the miR-125 family. In addition, we confirmed that Lin28a also plays a role as a MEG and affects ZGA at the 2C stage, without affecting oocyte maturation or fertilization. Thus, we provide the first report indicating that the miR-125 family plays a crucial role in regulating MEGs related to the 2C block and in regulating ZGA through methods such as affecting Sebox and Lin28a in oocytes and embryos.

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

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.

scholarly journals DPPA2 and DPPA4 are necessary to establish a totipotent state in mouse embryonic stem cells

2018 ◽  
Author(s):  
Alberto De Iaco ◽  
Alexandre Coudray ◽  
Julien Duc ◽  
Didier Trono
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Zygotic Genome Activation ◽  
Cell Stage ◽  
Oocyte Expression ◽  
Genome Activation ◽  
Zygotic Genome

AbstractAfter fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through so-called zygotic genome activation (ZGA), occurring in the mouse at the 2-cell stage. Amongst the first elements to be transcribed are the Dux gene, the product of which secondarily induces a wide array of ZGA genes, and a subset of evolutionary recent LINE-1 retrotransposons, which regulate chromatin accessibility in the early embryo. The maternally-inherited factors that activate Dux and LINE-1 transcription have so far remained unknown. Here we identify the paralog proteins DPPA2 and DPPA4 as responsible for this process.

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

2017 ◽  
pp. 245-257 ◽  
Author(s):  
Veronika Benesova ◽  
Veronika Kinterova ◽  
Jiri Kanka ◽  
Tereza Toralova
Keyword(s):  
Embryo Development ◽  
Bovine Embryo ◽  
Zygotic Genome Activation ◽  
Scf Complex ◽  
Genome Activation ◽  
Zygotic Genome

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

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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