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The International Journal of... 2019Monozygotic (MZ) polyembryony is a strategy to increase the output of a single zygote, thereby producing more offspring from a limited number of oocytes. However, MZ... (Review)
Review
Monozygotic (MZ) polyembryony is a strategy to increase the output of a single zygote, thereby producing more offspring from a limited number of oocytes. However, MZ twins and multiples (multiplets) of mammals occur rarely in nature, while their generation has been more successful experimentally. In this work, we review some of the methodological, biological and field aspects of experimental MZ polyembryony in mammals. First attempts of mechanical bisection of 2-cell stage rodent embryos provided a proof-of-principle for the survival and independent development of both blastomeres. Subsequently, experiments in other species, particularly sheep and bovine, allowed 2 methods of embryo multiplication to become routine: the separation or biopsy of blastomeres from cleavage-stage embryos and the bisection of morulae and blastocysts. We discuss how the preferable stage of bisection and the success rate can be species-specific. The scope that profited most from experimental MZ polyembryony is the production of additional copies of elite livestock individuals, the reduction of interindividual variation in test groups and the possibility of investigating discordant phenotypic traits in the same genomic background, for instance, comparing an affected twin with its healthy co-twin. By contrast, the original motivation for experimental polyembryony - efficiently generating more offspring out of the same zygote - has not been fulfilled yet. Although embryo splitting leads to an increase in quantity, there is a loss of embryo quality, thus, there is no real gain from artificially generated embryos (yet) in the field of medically assisted reproduction. In conclusion, mammalian zygotes have the regulative capacity to be polyembryonic, but this is not obligate.
Topics: Animals; Blastocyst; Blastomeres; Breeding; Cattle; Embryo, Mammalian; Embryonic Development; Female; Sheep; Twins, Monozygotic; Zygote
PubMed: 31058293
DOI: 10.1387/ijdb.190016mb -
Genes Oct 2022The 3D chromatin structure within the nucleus is important for gene expression regulation and correct developmental programs. Recently, the rapid development of... (Review)
Review
The 3D chromatin structure within the nucleus is important for gene expression regulation and correct developmental programs. Recently, the rapid development of low-input chromatin conformation capture technologies has made it possible to study 3D chromatin structures in gametes, zygotes and early embryos in a variety of species, including flies, vertebrates and mammals. There are distinct 3D chromatin structures within the male and female gametes. Following the fertilization of male and female gametes, fertilized eggs undergo drastic epigenetic reprogramming at multi levels, including the 3D chromatin structure, to convert the terminally differentiated gamete state into the totipotent state, which can give rise to an individual. However, to what extent the 3D chromatin structure reorganization is evolutionarily conserved and what the underlying mechanisms are for the tremendous reorganization in early embryos remain elusive. Here, we review the latest findings on the 3D chromatin structure reorganization during embryogenesis, and discuss the convergent and divergent reprogramming patterns and key molecular mechanisms for the 3D chromatin structure reorganization from gametes to embryos in different species. These findings shed light on how the 3D chromatin structure reorganization contribute to embryo development in different species. The findings also indicate the role of the 3D chromatin structure on the acquisition of totipotent developmental potential.
Topics: Animals; Male; Female; Germ Cells; Chromatin; Embryonic Development; Zygote; Cell Nucleus; Mammals
PubMed: 36292750
DOI: 10.3390/genes13101864 -
The Keio Journal of Medicine Jun 2020We present the most recent research results on the creation of pigs that can accept human cells. Pigs in which grafted human cells can flourish are essential for studies... (Review)
Review
We present the most recent research results on the creation of pigs that can accept human cells. Pigs in which grafted human cells can flourish are essential for studies of the production of human organs in the pig and for verification of the efficacy of cells and tissues of human origin for use in regenerative therapy. First, against the background of a worldwide shortage of donor organs, the need for future medical technology to produce human organs for transplantation is discussed. We then describe proof-of-concept studies in small animals used to produce human organs. An overview of the history of studies examining the induction of immune tolerance by techniques involving fertilized animal eggs and the injection of human cells into fetuses or neonatal animals is also presented. Finally, current and future prospects for producing pigs that can accept human cells and tissues for experimental purposes are discussed.
Topics: Animals; Animals, Genetically Modified; Animals, Newborn; Bioreactors; Blastocyst; Embryo Transfer; Fetus; Humans; Immune Tolerance; Induced Pluripotent Stem Cells; Organ Transplantation; Regenerative Medicine; Swine; Transplantation, Heterologous; Zygote
PubMed: 31391348
DOI: 10.2302/kjm.2019-0006-OA -
The Journal of Reproduction and... Apr 2022The zygotic genome is transcriptionally silent immediately after fertilization. In mice, initial activation of the zygotic genome occurs in the middle of the one-cell... (Review)
Review
The zygotic genome is transcriptionally silent immediately after fertilization. In mice, initial activation of the zygotic genome occurs in the middle of the one-cell stage. At the mid-to-late two-cell stage, a burst of gene activation occurs after the second round of DNA replication, and the profile of transcribed genes changes dramatically. These two phases of gene activation are called minor and major zygotic gene activation (ZGA), respectively. As they mark the beginning of the gene expression program, it is important to elucidate gene expression regulation during these stages. This article reviews the outcomes of studies that have clarified the profiles and regulatory mechanisms of ZGA.
Topics: Animals; DNA Replication; Embryonic Development; Gene Expression Regulation, Developmental; Genome; Mice; Transcriptional Activation; Zygote
PubMed: 35034936
DOI: 10.1262/jrd.2021-129 -
Nature Communications Jun 2023Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been...
Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been revealed for the totipotency regulatory network around the zygotic genome activation (ZGA) period. However, how the dissolution of the totipotency network is triggered to ensure the timely embryonic development following ZGA is largely unknown. In this study, we identify the unexpected role of a highly expressed 2-cell (2C) embryo specific transcription factor, ZFP352, in facilitating the dissolution of the totipotency network. We find that ZFP352 has selective binding towards two different retrotransposon sub-families. ZFP352 coordinates with DUX to bind the 2C specific MT2_Mm sub-family. On the other hand, without DUX, ZFP352 switches affinity to bind extensively onto SINE_B1/Alu sub-family. This leads to the activation of later developmental programs like ubiquitination pathways, to facilitate the dissolution of the 2C state. Correspondingly, depleting ZFP352 in mouse embryos delays the 2C to morula transition process. Thus, through a shift of binding from MT2_Mm to SINE_B1/Alu, ZFP352 can trigger spontaneous dissolution of the totipotency network. Our study highlights the importance of different retrotransposons sub-families in facilitating the timely and programmed cell fates transition during early embryogenesis.
Topics: Animals; Mice; Embryonic Development; Gene Expression Regulation, Developmental; Retroelements; Solubility; Transcription Factors; Zygote
PubMed: 37339952
DOI: 10.1038/s41467-023-39344-1 -
Genome Biology Apr 2023N-methyladenosine (mA) modification has been shown to regulate RNA metabolism. Here, we investigate mA dynamics during maternal-to-zygotic transition (MZT) in mice...
N-methyladenosine (mA) modification has been shown to regulate RNA metabolism. Here, we investigate mA dynamics during maternal-to-zygotic transition (MZT) in mice through multi-omic analysis. Our results show that mA can be maternally inherited or de novo gained after fertilization. Interestingly, mA modification on maternal mRNAs not only correlates with mRNA degradation, but also maintains the stability of a small group of mRNAs thereby promoting their translation after fertilization. We identify Ythdc1 and Ythdf2 as key mA readers for mouse preimplantation development. Our study reveals a key role of mA mediated RNA metabolism during MZT in mammals.
Topics: Animals; Mice; RNA, Messenger; Reading; Zygote; Embryonic Development; Mammals; Writing; Gene Expression Regulation, Developmental
PubMed: 37024923
DOI: 10.1186/s13059-023-02918-9 -
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 -
The Plant Cell Sep 2017The formation of a zygote via the fusion of an egg and sperm cell and its subsequent asymmetric division herald the start of the plant's life cycle. Zygotic genome...
The formation of a zygote via the fusion of an egg and sperm cell and its subsequent asymmetric division herald the start of the plant's life cycle. Zygotic genome activation (ZGA) is thought to occur gradually, with the initial steps of zygote and embryo development being primarily maternally controlled, and subsequent steps being governed by the zygotic genome. Here, using maize () as a model plant system, we determined the timing of zygote development and generated RNA-seq transcriptome profiles of gametes, zygotes, and apical and basal daughter cells. ZGA occurs shortly after fertilization and involves ∼10% of the genome being activated in a highly dynamic pattern. In particular, genes encoding transcriptional regulators of various families are activated shortly after fertilization. Further analyses suggested that chromatin assembly is strongly modified after fertilization, that the egg cell is primed to activate the translational machinery, and that hormones likely play a minor role in the initial steps of early embryo development in maize. Our findings provide important insights into gamete and zygote activity in plants, and our RNA-seq transcriptome profiles represent a comprehensive, unique RNA-seq data set that can be used by the research community.
Topics: Body Patterning; Cell Cycle; Cell Separation; Chromatin; Fertilization; Gene Expression Regulation, Plant; Genes, Plant; Genome, Plant; Germ Cells, Plant; Histones; Indoleacetic Acids; Oryza; Reproducibility of Results; Seeds; Sequence Analysis, RNA; Signal Transduction; Time Factors; Transcription Factors; Transcriptome; Zea mays; Zygote
PubMed: 28814645
DOI: 10.1105/tpc.17.00099 -
Open Biology Jun 2022POUV is a relatively newly emerged class of POU transcription factors present in jawed vertebrates (Gnathostomata). The function of POUV-class proteins is inextricably... (Review)
Review
POUV is a relatively newly emerged class of POU transcription factors present in jawed vertebrates (Gnathostomata). The function of POUV-class proteins is inextricably linked to zygotic genome activation (ZGA). A large body of evidence now extends the role of these proteins to subsequent developmental stages. While some functions resemble those of other POU-class proteins and are related to neuroectoderm development, others have emerged . The most notable of the latter functions is pluripotency control by Oct4 in mammals. In this review, we focus on these functions in the best-studied species harbouring POUV proteins-zebrafish, (anamniotes) and mammals (amniotes). Despite the broad diversity of their biological functions in vertebrates, POUV proteins exert a common feature related to their role in safeguarding the undifferentiated state of cells. Here we summarize numerous pieces of evidence for these specific functions of the POUV-class proteins and recap available loss-of-function data.
Topics: Animals; Gene Expression Regulation, Developmental; Mammals; Xenopus laevis; Zebrafish; Zebrafish Proteins; Zygote
PubMed: 35765816
DOI: 10.1098/rsob.220065 -
The International Journal of... 2019Early embryonic development is characterized by a plethora of very complex and simultaneously operating processes, which are constantly changing cellular morphology and... (Review)
Review
Early embryonic development is characterized by a plethora of very complex and simultaneously operating processes, which are constantly changing cellular morphology and behaviour. After fertilization, blastomeres of the newly created embryo undergo global epigenetic changes and simultaneously initiate transcription from the zygotic genome and differentiation forming separate cell lineages. Some of these mechanisms were extensively studied during the last several decades and valuable insight was gained into how these processes are regulated at the molecular level. We have, however, a still very limited understanding of how multiple events are coordinated during rapid development of an early mammalian embryo. In this review, we discuss some aspects of early embryonic development in mammals, namely the fidelity of chromosome segregation and occurrence of aneuploidy, as well as the clinical applications of cell cycle monitoring in human embryos.
Topics: Aneuploidy; Animals; Blastomeres; Cell Cycle; Chromosome Segregation; Embryo, Mammalian; Embryonic Development; Female; Humans; Pregnancy; Spindle Apparatus; Zygote
PubMed: 30785212
DOI: 10.1387/ijdb.180400ma