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Trends in Molecular Medicine Nov 2015In 1999, Tesarik and Greco reported that they could predict the developmental potential of human zygotes from a single static evaluation of their pronuclei. This was... (Review)
Review
In 1999, Tesarik and Greco reported that they could predict the developmental potential of human zygotes from a single static evaluation of their pronuclei. This was based on the distribution and number of specific nuclear organelles - the nucleoli. Recent studies in mice show that nucleoli play a key role in parental genome restructuring after fertilization, and that interfering with this process may lead to developmental failure. These studies thus support the Tesarik-Greco evaluation as a potentially useful method for selecting high-quality embryos in human assisted reproductive technologies. In this opinion article we discuss recent evidence linking nucleoli to parental genome reprogramming, and ask whether nucleoli can mirror or be used as representative markers of embryonic parameters such as chromosome content or DNA fragmentation.
Topics: Animals; Cell Nucleolus; DNA Fragmentation; Embryo, Mammalian; Epigenesis, Genetic; Fertilization; Genome, Human; Humans; Mice; Oocytes; Reproductive Techniques, Assisted; Zygote
PubMed: 26494190
DOI: 10.1016/j.molmed.2015.09.005 -
Nature Cell Biology Feb 2016The first hours of mammalian embryogenesis are devoted to extensive epigenetic reprogramming. One hallmark is active demethylation of the paternal genome by Tet...
The first hours of mammalian embryogenesis are devoted to extensive epigenetic reprogramming. One hallmark is active demethylation of the paternal genome by Tet (ten-eleven translocation) enzymes. However, the process is now shown to be Tet-independent at first, with Tet enzymes only counteracting hitherto underappreciated de novo DNA methylation activity in later zygotic stages.
Topics: 5-Methylcytosine; Animals; Cellular Reprogramming; Cytosine; DNA Methylation; Epigenesis, Genetic; Zygote
PubMed: 26820436
DOI: 10.1038/ncb3304 -
Science (New York, N.Y.) Apr 2007Maternal gene products drive early development when the newly formed embryo is transcriptionally inactive. During the maternal-zygotic transition, embryonic... (Review)
Review
Maternal gene products drive early development when the newly formed embryo is transcriptionally inactive. During the maternal-zygotic transition, embryonic transcription is initiated and many maternal RNAs are degraded. Multiple mechanisms regulate the birth of zygotic RNAs and the death of maternal RNAs. Genome activation appears to rely in part on the sequestration of transcriptional repressors by the exponentially increasing amount of DNA during cleavage divisions. Maternal RNA degradation is induced by the binding of proteins and microRNAs to the 3' untranslated region of target RNAs.
Topics: 3' Untranslated Regions; Animals; Cell Cycle; Embryonic Development; Female; Gene Expression Regulation, Developmental; Gene Silencing; MicroRNAs; RNA Stability; RNA, Messenger; RNA, Messenger, Stored; RNA-Binding Proteins; Transcription, Genetic; Zygote
PubMed: 17446392
DOI: 10.1126/science.1140693 -
The Journal of Reproduction and... Aug 2007Zygotic gene activation (ZGA) is the first event of gene expression after fertilization. Following fertilization, ZGA occurs within a short time interval depending on... (Review)
Review
Zygotic gene activation (ZGA) is the first event of gene expression after fertilization. Following fertilization, ZGA occurs within a short time interval depending on the animal species. Until ZGA, maternal proteins and transcripts stored in oocytes control embryonic development, indicating the importance of maternal factors for development. Somatic cell cloning also proves the potential of oocyte to reprogram the differentiated cell nuclei to embryonic nuclei. Recent studies show that the epigenetic modifications of nuclei play important roles in controlling gene expression during ZGA. However, the mechanisms that control ZGA remain largely unknown. This review will cover the current understanding of ZGA. Specifically, it will focus on the maternal factors that control gene expression during early embryogenesis.
Topics: Animals; Gene Expression Regulation, Developmental; Mammals; Oocytes; Transcriptional Activation; Zygote
PubMed: 17827882
DOI: 10.1262/jrd.19029 -
Microscopy and Microanalysis : the... Dec 2017Confocal microscopy was used to image stages of equine zygote development, at timed intervals, after intracytoplasmic sperm injection (ICSI) of oocytes that were matured...
Confocal microscopy was used to image stages of equine zygote development, at timed intervals, after intracytoplasmic sperm injection (ICSI) of oocytes that were matured in vivo or in vitro. After fixation for 4, 6, 8, 12, or 16 h after ICSI, zygotes were incubated with α/β tubulin antibodies and human anticentromere antibody (CREST/ACA), washed, incubated in secondary antibodies, conjugated to either Alexa 488 or Alexa 647, and incubated with 561-Phalloidin and Hoechst 33258. An Olympus IX81 spinning disk confocal microscope was used for imaging. Data were analyzed using χ 2 and Fisher's exact tests. Minor differences in developmental phases were observed for oocytes matured in vivo or in vitro. Oocytes formed pronuclei earlier when matured in vivo (67% at 6 h and 80% at 8 h) than in vitro (13% at 6 and 8 h); 80% of oocytes matured in vitro formed pronuclei by 12 h. More (p=0.04) zygotes had atypical phenotypes, indicative of a failure of normal zygote development, when oocyte maturation occurred in vitro versus in vivo (30 and 11%, respectively). Some potential zygotes from oocytes matured in vivo had normal phenotypes, although development appeared to be delayed or arrested. Confocal microscopy provided a feasible method to assess equine zygote development using limited samples.
Topics: Animals; Fertilization; Horses; Microinjections; Microscopy, Confocal; Microscopy, Fluorescence; Time Factors; Zygote
PubMed: 29208065
DOI: 10.1017/S1431927617012740 -
Cellular and Molecular Life Sciences :... May 2020Maternal RNAs and proteins in the oocyte contribute to early embryonic development. After fertilization, these maternal factors are cleared and embryonic development is... (Review)
Review
Maternal RNAs and proteins in the oocyte contribute to early embryonic development. After fertilization, these maternal factors are cleared and embryonic development is determined by an individual's own RNAs and proteins, in a process called the maternal-to-zygotic transition. Zygotic transcription is initially inactive, but is eventually activated by maternal transcription factors. The timing and molecular mechanisms involved in zygotic genome activation (ZGA) have been well-described in many species. Among birds, a transcriptome-based understanding of ZGA has only been explored in chickens by RNA sequencing of intrauterine embryos. RNA sequencing of chicken intrauterine embryos, including oocytes, zygotes, and Eyal-Giladi and Kochav (EGK) stages I-X has enabled the identification of differentially expressed genes between consecutive stages. These studies have revealed that there are two waves of ZGA: a minor wave at the one-cell stage (shortly after fertilization) and a major wave between EGK.III and EGK.VI (during cellularization). In the chicken, the maternal genome is activated during minor ZGA and the paternal genome is quiescent until major ZGA to avoid transcription from supernumerary sperm nuclei. In this review, we provide a detailed overview of events in intrauterine embryonic development in birds (and particularly in chickens), as well as a transcriptome-based analysis of ZGA.
Topics: Animals; Chick Embryo; Chickens; Embryonic Development; Gene Expression Regulation, Developmental; Genome; Oocytes; RNA, Messenger, Stored; Transcriptome; Zygote
PubMed: 31728579
DOI: 10.1007/s00018-019-03360-6 -
Protein & Cell Nov 2014The active DNA demethylation in early embryos is essential for subsequent development. Although the zygotic genome is globally demethylated, the DNA methylation of... (Review)
Review
The active DNA demethylation in early embryos is essential for subsequent development. Although the zygotic genome is globally demethylated, the DNA methylation of imprinted regions, part of repeat sequences and some gamete-specific regions are maintained. Recent evidence has shown that multiple proteins and biological pathways participate in the regulation of active DNA demethylation, such as TET proteins, DNA repair pathways and DNA methyltransferases. Here we review the recent understanding regarding proteins associated with active DNA demethylation and the regulatory networks controlling the active DNA demethylation in early embryos.
Topics: Animals; DNA Methylation; Embryo, Mammalian; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Genome; Humans; Mice; Models, Genetic; Zygote
PubMed: 25152302
DOI: 10.1007/s13238-014-0095-3 -
Current Topics in Developmental Biology 2015Fertilization marks the turnover from the gametophyte to sporophyte generation in higher plants. After fertilization, sporophytic development undergoes genetic turnover... (Review)
Review
Fertilization marks the turnover from the gametophyte to sporophyte generation in higher plants. After fertilization, sporophytic development undergoes genetic turnover from maternal to zygotic control: the maternal-to-zygotic transition (MZT). The MZT is thought to be critical for early embryogenesis; however, little is known about the time course or developmental impact of the MZT in higher plants. Here, we discuss what is known in the field and focus on techniques used in relevant studies and their limitations. Some significant questions and technical requirements for further investigations are also discussed.
Topics: Gene Expression Regulation, Plant; Magnoliopsida; Models, Biological; Seeds; Zygote
PubMed: 26358879
DOI: 10.1016/bs.ctdb.2015.06.006 -
Scientific Reports Oct 2018Here, we describe an expansion of the typical DNA size limitations associated with CRISPR knock-in technology, more specifically, the physical extent to which mouse...
Here, we describe an expansion of the typical DNA size limitations associated with CRISPR knock-in technology, more specifically, the physical extent to which mouse genomic DNA can be replaced with donor (in this case, human) DNA at an orthologous locus by zygotic injection. Driving our efforts was the desire to create a whole animal model that would replace 17 kilobase pairs (kbp) of the mouse Bcl2l11 gene with the corresponding 25-kbp segment of human BCL2L11, including a conditionally removable segment (2.9-kbp) of intron 2, a cryptic human exon immediately 3' of this, and a native human exon some 20 kbp downstream. Using two methods, we first carried out the replacement by employing a combination of bacterial artificial chromosome recombineering, classic embryonic stem cell (ESC) targeting, dual selection, and recombinase-driven cassette removal (ESC/Blastocyst Approach). Using a unique second method, we employed the same vector (devoid of its selectable marker cassettes), microinjecting it along with redundant single guide RNAs (sgRNAs) and Cas9 mRNA into mouse zygotes (CRISPR/Zygote Approach). In both instances, we were able to achieve humanization of Bcl2l11 to the extent designed, remove all selection cassettes, and demonstrate the functionality of the conditionally removable, loxP-flanked, 2.9-kbp intronic segment.
Topics: Animals; Bcl-2-Like Protein 11; Blastocyst; CRISPR-Cas Systems; Embryonic Stem Cells; Gene Editing; Humans; Introns; Mice; Microinjections; RNA, Guide, CRISPR-Cas Systems; Zygote
PubMed: 30301924
DOI: 10.1038/s41598-018-33408-9 -
Current Topics in Developmental Biology 2015During the maternal-to-zygotic transition (MZT), major changes in cell cycle regulation coincide with large-scale zygotic genome activation. In this chapter, we discuss... (Review)
Review
During the maternal-to-zygotic transition (MZT), major changes in cell cycle regulation coincide with large-scale zygotic genome activation. In this chapter, we discuss the current understanding of how the cell cycle is remodeled over the course of the Drosophila MZT, and how the temporal precision of this event is linked to contemporaneous alterations in genome-wide chromatin structure and transcriptional activity. The cell cycle is initially lengthened during the MZT by activation of the DNA replication checkpoint but, subsequently, zygotically supplied factors are essential for establishing lasting modifications to the cell cycle.
Topics: Animals; Blastula; Cell Cycle; Drosophila melanogaster; Genome, Insect; Transcriptional Activation; Zygote
PubMed: 26358872
DOI: 10.1016/bs.ctdb.2015.06.002