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Zygote (Cambridge, England) Aug 2023Fertilization failure (FF) and zygotic arrest after ICSI have a huge effect on both patients and clinicians, but both problems are usually unexpected and cannot be... (Review)
Review
Fertilization failure (FF) and zygotic arrest after ICSI have a huge effect on both patients and clinicians, but both problems are usually unexpected and cannot be properly diagnosed. Fortunately, in recent years, gene sequencing has allowed the identification of multiple genetic variants underlying failed ICSI outcomes, but the use of this approach is still far from routine in the fertility clinic. In this systematic review, the genetic variants associated with FF, abnormal fertilization and/or zygotic arrest after ICSI are compiled and analyzed. Forty-seven studies were included. Data from 141 patients carrying 121 genetic variants affecting 16 genes were recorded and analyzed. In total, 27 variants in (in 50 men) and 26 variants in (in 24 women) are two of the factors related to oocyte activation failure that could explain a high percentage of male-related and female-related FF. Additional variants identified were reported in , and (in men), and , , , , , , and (in women). Most of these variants are pathogenic or potentially pathogenic (89/121, 72.9%), as demonstrated by experimental and/or approaches. Most individuals carried bi-allelic variants (89/141, 63.1%), but pathogenic variants in heterozygosity have been identified for and . Clinical treatment options for affected individuals, such as chemical-assisted oocyte activation (AOA) or cRNA injection in the oocyte, are still experimental. In conclusion, a genetic study of known pathogenic variants may help in diagnosing recurrent FF and zygotic arrest and guide patient counselling and future research perspectives.
Topics: Male; Female; Animals; Sperm Injections, Intracytoplasmic; Zygote; Oocytes; Fertilization
PubMed: 37212058
DOI: 10.1017/S096719942300014X -
Food and Chemical Toxicology : An... May 2023Acrylamide (ACR) is an important chemical raw material for wastewater treatment, paper industry and textile industry, which is widely exposed from occupational,...
Acrylamide (ACR) is an important chemical raw material for wastewater treatment, paper industry and textile industry, which is widely exposed from occupational, environmental and dietary situation. ACR has neurotoxicity, genotoxicity, potential carcinogenicity and reproductive toxicity. Recent study indicates that ACR affected oocyte maturation quality. In the present study, we reported the effects of ACR exposure on zygotic genome activation (ZGA) in embryos and its related mechanism. Our results showed that ACR treatment caused 2-cell arrest in mouse embryos, indicating the failure of ZGA, which was confirmed by decreased global transcription levels and aberrant expression of ZGA-related and maternal factors. We found that histone modifications such as H3K9me3, H3K27me3 and H3K27ac levels were altered, and this might be due to the occurrence of DNA damage, showing with positive γ-H2A.X signal. Moreover, mitochondrial dysfunction and high levels of ROS were detected in ACR treated embryos, indicating that ACR induced oxidative stress, and this might further cause abnormal distribution of endoplasmic reticulum, Golgi apparatus and lysosomes. In conclusion, our results indicated that ACR exposure disrupted ZGA by inducing mitochondria-based oxidative stress, which further caused DNA damage, aberrant histone modifications and organelles in mouse embryos.
Topics: Mice; Animals; Acrylamide; Zygote; Oxidative Stress; Protein Processing, Post-Translational; DNA Damage
PubMed: 36997053
DOI: 10.1016/j.fct.2023.113753 -
Current Opinion in Genetics &... Oct 2020After fertilization, mouse embryos go through preimplantation development to give rise to blastocyst. Two key molecular events, zygotic genome activation (ZGA) and the... (Review)
Review
After fertilization, mouse embryos go through preimplantation development to give rise to blastocyst. Two key molecular events, zygotic genome activation (ZGA) and the first cell lineage specification, are essential for the process. Recent advances in low-input epigenomics profiling techniques allow the analysis of these events at a molecular level, which revealed a critical role of epigenetic and chromatin reprogramming in ZGA and the first cell lineage specification. Additionally, the establishment of an in vitro embryonic stem cell (ESC) to two-cell embryo-like conversion system have also contributed to the molecular understanding of preimplantation development. In this review, we summarize recent advances in epigenetic regulation of mouse preimplantation development, point out the remaining questions, and propose strategies to tackle these questions.
Topics: Animals; Blastocyst; Embryonic Development; Embryonic Stem Cells; Epigenesis, Genetic; Female; Genome; Humans; Pregnancy; Zygote
PubMed: 32563750
DOI: 10.1016/j.gde.2020.05.015 -
Current Topics in Developmental Biology 2015In Caenorhabditis elegans, the first zygotic transcription can be detected in the 4-cell stage C. elegans embryo, a little over 2h after fertilization. However, early... (Review)
Review
In Caenorhabditis elegans, the first zygotic transcription can be detected in the 4-cell stage C. elegans embryo, a little over 2h after fertilization. However, early development until the onset of gastrulation at approximately the 28-cell stage takes place normally even in the absence of zygotic transcription. Therefore, posttranslational and posttranscriptional regulation of the maternal proteins and mRNAs, respectively, that are loaded into the developing oocytes is sufficient to direct development prior to gastrulation. Protein phosphorylation is extensively used throughout the C. elegans maternal-to-zygotic transition (MZT): (1) for maternal protein activation, (2) for coordination of the meiotic and mitotic cell cycle, (3) to mark specific proteins for degradation, and/or (4) to switch the biochemical activity of specific proteins. Maternally loaded mRNAs are regulated primarily by a set of maternal RNA-binding proteins (RBPs), each of which binds to sometimes overlapping target sequences within the mRNA 3'UTRs and either promotes or inhibits translation. Most maternal transcripts are uniformly distributed throughout the embryo but specific transcripts are translated only in certain blastomeres. This control is achieved by the asymmetric distribution of the maternal RBPs, such that the blastomere-specific constellation of RBPs present, and their relative levels, determines the translational readout for their target transcripts. In certain well-studied cases, such as the specification of the sole endodermal precursor in the 8-cell embryo, the maternal transcripts and proteins along with their directly targeted zygotic genes have been identified.
Topics: Animals; Caenorhabditis elegans; Embryo, Nonmammalian; Female; Fertilization; Gene Expression Regulation, Developmental; Models, Biological; Zygote
PubMed: 26358869
DOI: 10.1016/bs.ctdb.2015.06.001 -
Current Opinion in Plant Biology Feb 2021In flowering plants, haploid gametes - an egg cell and a sperm cell fuse to form the first diploid cell - the zygote. The zygote is the progenitor stem cell that gives... (Review)
Review
In flowering plants, haploid gametes - an egg cell and a sperm cell fuse to form the first diploid cell - the zygote. The zygote is the progenitor stem cell that gives rise to all the embryonic and post embryonic tissues and organs. Unlike animals, both maternal and paternal gene products participate in the initial development of zygotes in plants. Here, we discuss recent advances in understanding of the zygotic transition and embryo initiation in angiosperms, including the role of parental contributions to gene expression in the zygote. We further discuss utilization of this knowledge in agricultural biotechnology through synthetic apomixis. Parthenogenesis obtained by manipulation of embryogenic factors, combined with mutations that bypass meiosis, enables clonal propagation of hybrid crops through seeds.
Topics: Animals; Crops, Agricultural; Diploidy; Gene Expression Regulation, Plant; Haploidy; Seeds; Zygote
PubMed: 33422964
DOI: 10.1016/j.pbi.2020.101993 -
International Journal of Molecular... Jan 2024Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a... (Review)
Review
Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA), marking the initiation of transcriptional control and gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis have enabled detailed explorations of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.
Topics: Animals; Pregnancy; Female; Male; Zygote; Histone Code; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Semen; Embryonic Development; Mammals
PubMed: 38338738
DOI: 10.3390/ijms25031459 -
Cell Research Sep 2022Chromatin remodeling is essential for epigenome reprogramming after fertilization. However, the underlying mechanisms of chromatin remodeling remain to be explored....
Chromatin remodeling is essential for epigenome reprogramming after fertilization. However, the underlying mechanisms of chromatin remodeling remain to be explored. Here, we investigated the dynamic changes in nucleosome occupancy and positioning in pronucleus-stage zygotes using ultra low-input MNase-seq. We observed distinct features of inheritance and reconstruction of nucleosome positioning in both paternal and maternal genomes. Genome-wide de novo nucleosome occupancy in the paternal genome was observed as early as 1 h after the injection of sperm into ooplasm. The nucleosome positioning pattern was continually rebuilt to form nucleosome-depleted regions (NDRs) at promoters and transcription factor (TF) binding sites with differential dynamics in paternal and maternal genomes. NDRs formed more quickly on the promoters of genes involved in zygotic genome activation (ZGA), and this formation is closely linked to histone acetylation, but not transcription elongation or DNA replication. Importantly, we found that NDR establishment on the binding motifs of specific TFs might be associated with their potential pioneer functions in ZGA. Further investigations suggested that the predicted factors MLX and RFX1 played important roles in regulating minor and major ZGA, respectively. Our data not only elucidate the nucleosome positioning dynamics in both male and female pronuclei following fertilization, but also provide an efficient method for identifying key transcription regulators during development.
Topics: Animals; Chromatin Assembly and Disassembly; Female; Fertilization; Male; Mice; Nucleosomes; Regulatory Factor X1; Semen; Zygote
PubMed: 35428874
DOI: 10.1038/s41422-022-00652-8 -
Cold Spring Harbor Protocols Aug 2017This protocol describes an example of complete zygote enucleation and transplantation of male and female pronuclei; however, single pronuclei can also be removed and...
This protocol describes an example of complete zygote enucleation and transplantation of male and female pronuclei; however, single pronuclei can also be removed and transplanted. In this method, pronuclei are removed without penetrating the plasma membrane of the zygote. Instead, they are withdrawn individually or together into a membrane-bound karyoplast that can then be fused with a recipient enucleated zygote using inactivated Sendai virus or electrofusion. Preincubation of the embryos in the presence of the cytoskeletal inhibitors cytochalasin B and colcemid is critical for the survival of the embryos during this microsurgical procedure. The protocol is divided into five parts: (1) isolating embryos, (2) making an enucleation/injection pipette, (3) enucleating a zygote, (4) preparing inactivated Sendai virus, and (5) introducing pronuclei into enucleated zygotes.
Topics: Animals; Cell Fusion; Cell Nucleus; Female; Male; Mice; Microinjections; Nuclear Transfer Techniques; Zygote
PubMed: 28765300
DOI: 10.1101/pdb.prot094417 -
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 -
FEBS Letters Sep 2018Since their discovery, the study of maternal mRNAs has led to the identification of mechanisms underlying their spatiotemporal regulation within the context of oogenesis... (Review)
Review
Since their discovery, the study of maternal mRNAs has led to the identification of mechanisms underlying their spatiotemporal regulation within the context of oogenesis and early embryogenesis. Following synthesis in the oocyte, maternal mRNAs are translationally silenced and sequestered into storage in cytoplasmic granules. At the same time, their unique distribution patterns throughout the oocyte and embryo are tightly controlled and connected to their functions in downstream embryonic processes. At certain points in oogenesis and early embryogenesis, maternal mRNAs are translationally activated to perform their functions in a timely manner. The cytoplasmic polyadenylation machinery is responsible for the translational activation of maternal mRNAs, and its role in initiating the maternal to zygotic transition events has recently come to light. Here, we summarize the current knowledge on maternal mRNA regulation, with particular focus on cytoplasmic polyadenylation as a mechanism for translational regulation.
Topics: Animals; Female; Gene Expression Regulation, Developmental; Humans; Oogenesis; Polyadenylation; RNA Interference; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Messenger, Stored; Zygote
PubMed: 29972882
DOI: 10.1002/1873-3468.13183