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zygote arrest

Sarah Wyck, Carolina Herrera, Cristina E Requena, Lilli Bittner, Petra Hajkova, Heinrich Bollwein, Raffaella Santoro
BACKGROUND: Reactive oxygen species (ROS)-induced oxidative stress is well known to play a major role in male infertility. Sperm are sensitive to ROS damaging effects because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. However, how oxidative DNA lesions in sperm affect early embryonic development remains elusive. RESULTS: Using cattle as model, we show that fertilization using sperm exposed to oxidative stress caused a major developmental arrest at the time of embryonic genome activation...
October 17, 2018: Epigenetics & Chromatin
Hongzheng Sun, Jian Kang, Jianmin Su, Jinjing Zhang, Lei Zhang, Xin Liu, Jingcheng Zhang, Fengyu Wang, Zhenzhen Lu, Xupeng Xing, HuanHuan Chen, Yong Zhang
Methionine adenosyltransferase II (MAT2A) is essential to the synthesis of S-adenosylmethionine, a major methyl donor, from L-methionine and ATP. Upon fertilization, zygotic genome activation (ZGA) marks the period that transforms the genome from transcriptional quiescence to robust transcriptional activity. During this period, embryonic epigenome undergoes extensive modifications, including histone methylation changes. However, whether MAT2A participates in histone methylation at the ZGA stage is unknown. Herein, we identified that MAT2A is a pivotal factor for ZGA in mouse embryos...
September 27, 2018: Biology of Reproduction
Wen-Xia He, Min Wu, Zhen Liu, Zhi Li, Yang Wang, Jian Zhou, Peng Yu, Xiao-Juan Zhang, Li Zhou, Jian-Fang Gui
Stem-loop binding protein (SLBP) has been revealed to bind to the stem-loop of replication-dependent histone mRNAs and to be required for replication-dependent histone mRNA metabolism in mammals. Zebrafish possesses two slbps and slbp1 is required for retinal neurogenesis. However, the detailed expression and function of slbp2 in zebrafish is still unknown. In this study, we first identified zebrafish slbp2 as an oocyte-specific maternal factor and then generated maternal-zygotic slbp2 F3 homozygous mutant (MZslbp2Δ4-/-) by CRISPR/Cas9...
September 5, 2018: RNA
Rui Gao, Chenfei Wang, Yawei Gao, Wenchao Xiu, Jiayu Chen, Xiaochen Kou, Yanhong Zhao, Yuhan Liao, Dandan Bai, Zhibin Qiao, Lei Yang, Mingzhu Wang, Ruge Zang, Xiaoyu Liu, Yanping Jia, Yanhe Li, Yalin Zhang, Jiqing Yin, Hong Wang, Xiaoping Wan, Wenqiang Liu, Yong Zhang, Shaorong Gao
Somatic cell nuclear transfer (SCNT) enables cloning of differentiated cells by reprogramming their nuclei to a totipotent state. However, successful full-term development of SCNT embryos is a low-efficiency process and arrested embryos frequently exhibit epigenetic abnormalities. Here, we generated genome-wide DNA methylation maps from mouse pre-implantation SCNT embryos. We identified widespread regions that were aberrantly re-methylated, leading to mis-expression of genes and retrotransposons important for zygotic genome activation...
September 6, 2018: Cell Stem Cell
Yin-Li Zhang, Long-Wen Zhao, Jue Zhang, Rongrong Le, Shu-Yan Ji, Chuan Chen, Yawei Gao, Dali Li, Shaorong Gao, Heng-Yu Fan
Mammalian oocytes and zygotes have the unique ability to reprogram a somatic cell nucleus into a totipotent state. SUV39H1/2-mediated histone H3 lysine-9 trimethylation (H3K9me3) is a major barrier to efficient reprogramming. How SUV39H1/2 activities are regulated in early embryos and during generation of induced pluripotent stem cells (iPSCs) remains unclear. Since expression of the CRL4 E3 ubiquitin ligase in oocytes is crucial for female fertility, we analyzed putative CRL4 adaptors (DCAFs) and identified DCAF13 as a novel CRL4 adaptor that is essential for preimplantation embryonic development...
September 14, 2018: EMBO Journal
Jinsong Liu
Life starts with a zygote, which is formed by the fusion of a haploid sperm and egg. The formation of a blastomere by cleavage division (nuclear division without an increase in cell size) is the first step in embryogenesis, after the formation of the zygote. Blastomeres are responsible for reprogramming the parental genome as a new embryonic genome for generation of the pluripotent stem cells which then differentiate by Waddington's epigenetic landscape to create a new life. Multiple authors over the past 150 years have proposed that tumors arises from development gone awry at a point within Waddington's landscape...
July 21, 2018: Seminars in Cancer Biology
Ken-Ichiro Abe, Satoshi Funaya, Dai Tsukioka, Machika Kawamura, Yutaka Suzuki, Masataka G Suzuki, Richard M Schultz, Fugaku Aoki
In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-cell stage, the function of minor ZGA is not well understood...
July 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
Daniel J Kaser, Berhan Bogale, Vishnudas Sarda, Leslie V Farland, Paige L Williams, Catherine Racowsky
OBJECTIVE: To determine whether [1] exposure of embryos to 5% oxygen (O2 ) from day 1 (D1) to D3, and then to 2% O2 from D3 to D5, improves total blastocyst yield, as compared with continuous exposure to 5% O2 ; and [2] extended culture in 2% O2 alters key metabolic processes and O2 -regulated gene expression in human preimplantation embryos. DESIGN: Randomized controlled trial. SETTING: Academic medical center. PATIENT(S): Bipronucleate and tripronucleate embryos donated for research...
June 2018: Fertility and Sterility
Dang Vinh Do, Bernhard Strauss, Engin Cukuroglu, Iain Macaulay, Keng Boon Wee, Tim Xiaoming Hu, Ruiz De Los Mozos Igor, Caroline Lee, Andrew Harrison, Richard Butler, Sabine Dietmann, Ule Jernej, John Marioni, Christopher W J Smith, Jonathan Göke, M Azim Surani
The RNA-binding protein SRSF3 (also known as SRp20) has critical roles in the regulation of pre-mRNA splicing. Zygotic knockout of Srsf3 results in embryo arrest at the blastocyst stage. However, SRSF3 is also present in oocytes, suggesting that it might be critical as a maternally inherited factor. Here we identify SRSF3 as an essential regulator of alternative splicing and of transposable elements to maintain transcriptome integrity in mouse oocyte. Using 3D time-lapse confocal live imaging, we show that conditional deletion of Srsf3 in fully grown germinal vesicle oocytes substantially compromises the capacity of germinal vesicle breakdown (GVBD), and consequently entry into meiosis...
2018: Cell Discovery
Bradford W Daigneault, Sandeep Rajput, George W Smith, Pablo J Ross
POU5F1 is a transcription factor and master regulator of cell pluripotency with indispensable roles in early embryo development and cell lineage specification. The role of embryonic POU5F1 in blastocyst formation and cell lineage specification differs between mammalian species but remains completely unknown in cattle. The CRISPR/Cas9 system was utilized for targeted disruption of the POU5F1 gene by direct injection into zygotes. Disruption of the bovine POU5F1 locus prevented blastocyst formation and was associated with embryonic arrest at the morula stage...
May 17, 2018: Scientific Reports
Mingtian Deng, Yongjie Wan, Zifei Liu, Caifang Ren, Guomin Zhang, Jing Pang, Yanli Zhang, Feng Wang
In mammals, their proper development during the early cleavage stages strongly relies on the gene products newly transcribed by zygotic genome activation (ZGA). Long noncoding RNAs (lncRNAs) have been characterized as key regulators of the ZGA process in mice and human. However, the ZGA stage has not yet been identified and epigenetic regulations of the ZGA process remain largely unknown in goats. Here, we show that ZGA occurred at the 8-cell stage in goats. During ZGA, tri-methylation of H3K9 was dynamically changed but maintained strong staining in development arrested embryos...
May 15, 2018: Biology of Reproduction
Cristina Fernández-Díez, Silvia González-Rojo, Marta Lombó, M Paz Herráez
Spermatozoa carry DNA damage that must be repaired by the oocyte machinery upon fertilization. Different strategies could be adopted by different vertebrates to face the paternal genotoxic damage. Mammals have strong sperm selection mechanisms and activate a zygotic DNA damage response (DDR) (including cell cycle arrest, DNA repair and alternative apoptosis) in order to guarantee the genomic conformity of the reduced progeny. However, external fertilizers, with different reproductive strategies, seem to proceed distinctively...
April 30, 2018: Biology Open
Ping Yuan, Lingyan Zheng, Hao Liang, Yu Li, Haijing Zhao, Ruiqi Li, Luhua Lai, Qingxue Zhang, Wenjun Wang
PURPOSE: Cleavage of the zygote during human reproduction is a key event of early embryonic development. The genetic events associated with idiopathic embryonic cleavage failure are not certain. Mutations in the tubulin beta 8 class VIII (TUBB8) gene have been reported to be associated with oocyte maturation, fertilization, and developmental arrest. Here, we aimed to assess the clinical and genetic characteristics of complete cleavage failure in fertilized eggs. METHODS: We have characterized a patient with a 9-year history of primary infertility in a non-consanguineous family from China...
July 2018: Journal of Assisted Reproduction and Genetics
Te-Sha Tsai, Justin C St John
Mitochondrial DNA (mtDNA) deficient metaphase II porcine oocytes are less likely to fertilize and more likely to arrest during preimplantation development. However, they can be supplemented with autologous populations of mitochondria at the time of fertilization, which significantly increases mtDNA copy number by the 2-cell stage due to the modulation of DNA methylation at a CpG island of the gene encoding the mtDNA-specific polymerase, POLG, and promotes preimplantation development. Although mitochondrial supplementation does not increase development rates or mtDNA copy number in oocytes with normal levels of mtDNA copy number, we tested whether this approach would also impact on chromosomal gene expression patterns in these oocytes at each stage of preimplantation development...
June 2018: Molecular Reproduction and Development
Giuliana D Clemente, Matthew R Hannaford, Hamze Beati, Katja Kapp, Jens Januschke, Eric R Griffis, Hans-Arno J Müller
Spindly was originally identified as a specific regulator of Dynein activity at the kinetochore. In early prometaphase, Spindly recruits the Dynein/Dynactin complex, promoting the establishment of stable kinetochore-microtubule interactions and progression into anaphase. While details of Spindly function in mitosis have been worked out in cultured human cells and in the C. elegans zygote, the function of Spindly within the context of an organism has not yet been addressed. Here, we present loss- and gain-of-function studies of Spindly using transgenic RNAi in Drosophila ...
March 30, 2018: Journal of Developmental Biology
Gláucia M Bragança, Ribrio Ivan T P Batista, Joanna Maria G Souza-Fabjan, Vivian A P Alfradique, Eduardo K N Arashiro, Isabel O Cosentino, Pedro Henrique N Pinto, Luiz Sérgio A Camargo, Jeferson F da Fonseca, Felipe Z Brandão
The present study evaluated the effect of four ovarian stimulation protocols on the follicular population and molecular status of cumulus-oocyte complexes (COCs). Twelve Santa Inês ewes (in a cross-over design) received 80 or 120mg FSH alone in a multiple-dose (MD80 and MD120) regimen or in combination with 300IU equine chorionic gonadotrophin (eCG) in a one-shot (OS80 and OS120) protocol. The follicular population, COC recovery rate, mean COCs per ewe and the rate of brilliant Cresyl blue-positive (BCB+) COCs were similar among treatments (P>0...
March 27, 2018: Reproduction, Fertility, and Development
Erika Toda, Yukinosuke Ohnishi, Takashi Okamoto
Upon double fertilization, one sperm cell fuses with the egg cell to form a zygote with a 1:1 maternal-to-paternal genome ratio (1m:1p), and another sperm cell fuses with the central cell to form a triploid primary endosperm cell with a 2m:1p ratio, resulting in formation of the embryo and the endosperm, respectively. The endosperm is known to be considerably sensitive to the ratio of the parental genomes. However, the effect of an imbalance of the parental genomes on zygotic development and embryogenesis has not been well studied, because it is difficult to reproduce the parental genome-imbalanced situation in zygotes and to monitor the developmental profile of zygotes without external effects from the endosperm...
April 27, 2018: Journal of Experimental Botany
Pengyu Cheng, Hongjuan Li, Linlin Yuan, Huiyong Li, Lele Xi, Junjie Zhang, Jin Liu, Yingdian Wang, Heping Zhao, Huixin Zhao, Shengcheng Han
The ERA ( E. coli RAS-like protein)-related GTPase (ERG) is a nuclear-encoded GTPase with two conserved domains: a GTPase domain and a K Homology (KH) domain. ERG plays a vital role in early seed development in Antirrhinum majus . However, the mechanism that regulates seed development remains unclear. Blasting the genome sequence revealed two homologies of ERG, AtERG1, and AtERG2 in Arabidopsis . In this study, we found that AtERG2 is localized in the mitochondria and binds mitochondrial 18S RNA. Promoter and transcript analyses indicated that AtERG2 was mainly expressed in the leaf vein, trichome, and ovule...
2018: Frontiers in Plant Science
Christoph Lippuner, Chandra Ramakrishnan, Walter U Basso, Marc W Schmid, Michal Okoniewski, Nicholas C Smith, Michael Hässig, Peter Deplazes, Adrian B Hehl
Cryptosporidium parvum is a major cause of diarrhoea in humans and animals. There are no vaccines and few drugs available to control C. parvum. In this study, we used RNA-Seq to compare gene expression in sporozoites and intracellular stages of C. parvum to identify genes likely to be important for successful completion of the parasite's life cycle and, thereby, possible targets for drugs or vaccines. We identified 3774 protein-encoding transcripts in C. parvum. Applying a stringent cut-off of eight fold for determination of differential expression, we identified 173 genes (26 coding for predicted secreted proteins) upregulated in sporozoites...
May 2018: International Journal for Parasitology
Jie Qian, Yueyue Chen, Ying Hu, Yingtian Deng, Yang Liu, Gang Li, Wenxuan Zou, Jie Zhao
Replication factor C (RFC) is a conserved eukaryotic complex consisting of RFC1/2/3/4/5. It plays important roles in DNA replication and the cell cycle in yeast and fruit fly. However, it is not very clear how RFC subunits function in higher plants, except for the Arabidopsis (At) subunits AtRFC1 and AtRFC3. In this study, we investigated the functions of AtRFC4 and found that loss of function of AtRFC4 led to an early sporophyte lethality that initiated as early as the elongated zygote stage, all defective embryos arrested at the two- to four-cell embryo proper stage, and the endosperm possessed six to eight free nuclei...
April 2018: Plant Journal: for Cell and Molecular Biology
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