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JBRA Assisted Reproduction May 2020The mitochondria are intracellular organelles, and just like the cell nucleus they have their own genome. They are extremely important for normal body functioning and... (Review)
Review
The mitochondria are intracellular organelles, and just like the cell nucleus they have their own genome. They are extremely important for normal body functioning and are responsible for ATP production - the main energy source for the cell. Mitochondrial diseases are associated with mutations in mitochondrial DNA and are inherited exclusively from the mother. They can affect organs that depend on energy metabolism, such as skeletal muscles, the cardiac system, the central nervous system, the endocrine system, the retina and liver, causing various incurable diseases. Mitochondrial replacement techniques provide women with mitochondrial defects a chance to have normal biological children. The goal of such treatment is to reconstruct functional oocytes and zygotes, in order to avoid the inheritance of mutated genes; for this the nuclear genome is withdrawn from an oocyte or zygotes, which carries mitochondrial mutations, and is implanted in a normal anucleated cell donor. Currently, the options of a couple to prevent the transmission of mitochondrial diseases are limited, and mitochondrial donation techniques provide women with mitochondrial defects a chance to have normal children. The nuclear genome can be transferred from oocytes or zygotes using techniques such as pronuclear transfer, spindle transfer, polar body transfer and germinal vesicle transfer. This study presents a review of developed mitochondrial substitution techniques, and its ability to prevent hereditary diseases.
Topics: Adult; DNA, Mitochondrial; Female; Genome, Mitochondrial; Humans; Male; Mitochondrial Diseases; Mitochondrial Replacement Therapy; Mutation; Oocytes; Parents; Zygote
PubMed: 32073245
DOI: 10.5935/1518-0557.20190086 -
Current Opinion in Cell Biology Feb 2022The genome of an early embryo undergoes significant remodelling at the epigenetic, transcriptional, and structural levels. New technological developments have made it... (Review)
Review
The genome of an early embryo undergoes significant remodelling at the epigenetic, transcriptional, and structural levels. New technological developments have made it possible to study 3D genome organisation in the zygote and early embryo of many different species. Recent studies in human embryos, zebrafish, medaka, and Xenopus have revealed that, similar to previous results in mouse and Drosophila, the zygotic genome is unstructured prior to zygotic genome activation. While these studies show that topologically associating domains are established coincident with zygotic genome activation across species, other 3D genome structures have more varied timing. Here, we review recent studies examining the timing and mechanisms of establishment of 3D genome organisation in the early embryo, and discuss similarities and differences between species. Investigating the establishment of 3D chromatin conformation in early embryos has the potential to reveal novel mechanisms of 3D genome organisation.
Topics: Animals; Chromatin; Drosophila; Drosophila Proteins; Gene Expression Regulation, Developmental; Genome; Mice; Zebrafish; Zygote
PubMed: 35065445
DOI: 10.1016/j.ceb.2021.12.004 -
PLoS Biology Jan 2021To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes....
To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes. In the fission yeast Schizosaccharomyces pombe, fertilization triggers the Mei3-Pat1-Mei2 signaling cascade, which represses subsequent mating and initiates meiosis. Here, we establish a degron system to specifically degrade proteins postfusion and demonstrate that mating blocks not only safeguard zygote ploidy but also prevent lysis caused by aberrant fusion attempts. Using long-term imaging and flow-cytometry approaches, we identify previously unrecognized and independent roles for Mei3 and Mei2 in zygotes. We show that Mei3 promotes premeiotic S-phase independently of Mei2 and that cell cycle progression is both necessary and sufficient to reduce zygotic mating behaviors. Mei2 not only imposes the meiotic program and promotes the meiotic cycle, but also blocks mating behaviors independently of Mei3 and cell cycle progression. Thus, we find that fungi preserve zygote ploidy and survival by at least 2 mechanisms where the zygotic fate imposed by Mei2 and the cell cycle reentry triggered by Mei3 synergize to prevent zygotic mating.
Topics: Cell Cycle; Cell Cycle Proteins; Fungal Proteins; Genes, Fungal; Mating Factor; Meiosis; Organisms, Genetically Modified; Ploidies; RNA-Binding Proteins; Recombination, Genetic; Schizosaccharomyces; Schizosaccharomyces pombe Proteins; Zygote
PubMed: 33406066
DOI: 10.1371/journal.pbio.3001067 -
Cell and Tissue Research Jan 2016The origin recognition complex (ORC) proteins, ORC1-6, are the first known proteins that bind DNA replication origins to mark the competency for the initiation of DNA... (Review)
Review
The origin recognition complex (ORC) proteins, ORC1-6, are the first known proteins that bind DNA replication origins to mark the competency for the initiation of DNA synthesis. These proteins have complex mechanisms of assembly into the ORC complex and unexpected localizations in the mitotic chromosomes, cytoplasm, and nuclear structures. The mammalian zygote is a potentially important model that may contribute to our understanding of the mechanisms and features influencing origin establishment and in the identification of other functions of the ORC proteins. Together with expected localizations to the chromatin during G1, we found an unexpected distribution in the cytoplasm that appeared to accumulate ORC proteins suggesting potential roles for ORC subunits in mitosis and chromatin segregation. ORC1, 2, 3, and 5 all localize to the area between the separating maternal chromosomes shortly after fertilization. ORC4 forms a cage around the set of chromosomes that will be extruded during polar body formation before it binds to the chromatin shortly before zygotic DNA replication. These data suggest that the ORC proteins may also play roles in preparing the cell for DNA replication in addition to their direct role in establishing functional replication origins.
Topics: Animals; DNA Replication; Female; Humans; Male; Origin Recognition Complex; Spermatozoa; Zygote
PubMed: 26453397
DOI: 10.1007/s00441-015-2296-3 -
Molecular Plant Sep 2021Fertilization constitutes a critical step in the plant life cycle during which the gamete genomes undergo chromatin dynamics in preparation for embryogenesis. In...
Fertilization constitutes a critical step in the plant life cycle during which the gamete genomes undergo chromatin dynamics in preparation for embryogenesis. In mammals, parental chromatin is extensively reprogrammed through the global erasure of DNA methylation. However, in flowering plants it remains unclear whether and how DNA methylation is remodeled in gametes and after fertilization in the zygote. In this study, we characterize DNA methylation patterns and investigate the function of DNA glycosylases in rice eggs, sperm, and unicellular zygotes and during embryogenesis. We found that DNA methylation is locally reconfigured after fertilization and is intensified during embryogenesis. Genetic, epigenomic, and transcriptomic analysis revealed that three rice DNA glycosylases, DNG702, DNG701, and DNG704, demethylate DNA at distinct genomic regions in the gametes and the zygote, and are required for zygotic gene expression and development. Collectively, these results indicate that active DNA demethylation takes place in the gametes and the zygote to locally remodel DNA methylation, which is critical for egg and zygote gene expression and reproduction in rice.
Topics: Arabidopsis; Chromatin; DNA Methylation; DNA, Plant; Germ Cells, Plant; Oryza; Plant Development; Zygote
PubMed: 34116223
DOI: 10.1016/j.molp.2021.06.006 -
Developmental Cell Aug 2018Parental genomes are initially separate in the zygote following fertilization. A recent study in Science by Reichmann et al. (2018) reveals that dual spindles assemble...
Parental genomes are initially separate in the zygote following fertilization. A recent study in Science by Reichmann et al. (2018) reveals that dual spindles assemble around the two pronuclei in mouse embryos to maintain separation of the two parental genomes through the first zygotic division.
Topics: Animals; Cell Nucleus; Fertilization; Genome; Mice; Zygote
PubMed: 30086299
DOI: 10.1016/j.devcel.2018.07.019 -
Fly Dec 2022The development of all animal embryos is initially directed by the gene products supplied by their mothers. With the progression of embryogenesis, the embryo's genome is... (Review)
Review
The development of all animal embryos is initially directed by the gene products supplied by their mothers. With the progression of embryogenesis, the embryo's genome is activated to command subsequent developments. This transition, which has been studied in many model animals, is referred to as the Maternal-to-Zygotic Transition (MZT). In many organisms, including flies, nematodes, and sea urchins, genes involved in Notch signaling are extensively influenced by the MZT. This signaling pathway is highly conserved across metazoans; moreover, it regulates various developmental processes. Notch signaling defects are commonly associated with various human diseases. The maternal contribution of its factors was first discovered in flies. Subsequently, several genes were identified from mutant embryos with a phenotype similar to mutants only upon the removal of the maternal contributions. Studies on these maternal genes have revealed various novel steps in the cascade of Notch signal transduction. Among these genes, and have been functionally characterized in recent studies. Therefore, in this review, we will focus on the roles of these two maternal genes in Notch signaling and discuss future research directions on its maternal function.
Topics: Humans; Animals; Gene Expression Regulation, Developmental; Zygote; Embryonic Development; Signal Transduction; Genome
PubMed: 36346359
DOI: 10.1080/19336934.2022.2139981 -
The International Journal of... 2009In mammals, the maternal and the paternal genome are not functionally equivalent and are both required for embryonic and postnatal development. The genome is organised... (Review)
Review
In mammals, the maternal and the paternal genome are not functionally equivalent and are both required for embryonic and postnatal development. The genome is organised differently in the oocyte as compared to sperm, in which the DNA is tightly packaged with protamines rather than with histones. The requirement of both the parental genomes for normal development is a consequence of differential epigenetic marking in oogenesis and spermatogenesis, at the regulatory elements that control genomic imprinting. These germ line-derived marks of DNA methylation are resistant to the global waves of demethylation that occur following fertilisation, and bring about the parental allele-specific expression of imprinted genes during development and after birth. Perturbation of the differential organisation of the maternally and paternally derived genomes, before fertilisation, or in the early embryo, can give rise to aberrant growth and developmental disorders in humans.
Topics: Animals; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Genomic Imprinting; Humans; Mammals; Models, Biological; Zygote
PubMed: 19378254
DOI: 10.1387/ijdb.082654rf -
Current Topics in Developmental Biology 2020Mammalian embryogenesis depends on maternal factors accumulated in eggs prior to fertilization and on placental transfers later in gestation. In this review, we focus on... (Review)
Review
Mammalian embryogenesis depends on maternal factors accumulated in eggs prior to fertilization and on placental transfers later in gestation. In this review, we focus on initial events when the organism has insufficient newly synthesized embryonic factors to sustain development. These maternal factors regulate preimplantation embryogenesis both uniquely in pronuclear formation, genome reprogramming and cell fate determination and more universally in regulating cell division, transcription and RNA metabolism. Depletion, disruption or inappropriate persistence of maternal factors can result in developmental defects in early embryos. To better understand the origins of these maternal effects, we include oocyte maturation processes that are responsible for their production. We focus on recent publications and reference comprehensive reviews that include earlier scientific literature of early mouse development.
Topics: Animals; Embryo, Mammalian; Embryonic Development; Female; Gene Expression Regulation, Developmental; Genome; Maternal Inheritance; Mice; Oocytes; Zygote
PubMed: 32591079
DOI: 10.1016/bs.ctdb.2019.10.006 -
Reproduction (Cambridge, England) Dec 2016Gametogenesis (spermatogenesis and oogenesis) is accompanied by the acquisition of gender-specific epigenetic marks, such as DNA methylation, histone modifications and... (Review)
Review
Gametogenesis (spermatogenesis and oogenesis) is accompanied by the acquisition of gender-specific epigenetic marks, such as DNA methylation, histone modifications and regulation by small RNAs, to form highly differentiated, but transcriptionally silent cell-types in preparation for fertilisation. Upon fertilisation, extensive global epigenetic reprogramming takes place to remove the previously acquired epigenetic marks and produce totipotent zygotic states. It is the aim of this review to delineate the cellular and molecular events involved in maternal, paternal and zygotic epigenetic reprogramming from the time of gametogenesis, through fertilisation, to the initiation of zygotic genome activation for preimplantation embryonic development. Recent studies have begun to uncover the indispensable functions of epigenetic players during gametogenesis, fertilisation and preimplantation embryo development, and a more comprehensive understanding of these early events will be informative for increasing pregnancy success rates, adding particular value to assisted fertility programmes.
Topics: Animals; Cellular Reprogramming; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; Male; Mice; Zygote
PubMed: 27601712
DOI: 10.1530/REP-16-0376