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zygote arrest

Bo Fu, Hong Ma, Di Liu
Pre-implantation embryo development encompasses several key developmental events, especially the activation of zygotic genome activation (ZGA)-related genes. Endogenous retroviruses (ERVs), which are regarded as "deleterious genomic parasites", were previously considered to be "junk DNA". However, it is now known that ERVs, with limited conservatism across species, mediate conserved developmental processes (e.g., ZGA). Transcriptional activation of ERVs occurs during the transition from maternal control to zygotic genome control, signifying ZGA...
February 12, 2019: International Journal of Molecular Sciences
Qian-Qian Sha, Jue Zhang, Heng-Yu Fan
In mammals, maternal-to-zygotic transition (MZT), or oocyte-to-embryo transition, begins with oocyte meiotic resumption due to the sequential translational activation and destabilization of dormant maternal transcripts stored in the ooplasm. It then continues with the elimination of maternal transcripts during oocyte maturation and fertilization and ends with the full transcriptional activation of the zygotic genome during embryonic development. A hallmark of MZT in mammals is its reliance on translation and the utilization of stored RNAs and proteins, rather than de novo transcription of genes, to sustain meiotic maturation and early development...
January 31, 2019: Biology of Reproduction
C Scarica, D Cimadomo, L Dovere, A Giancani, M Stoppa, A Capalbo, F M Ubaldi, L Rienzi, R Canipari
PURPOSE: To investigate the association of cumulus cell (CC)-related expression of a selected cluster of key genes (PTGS2, CAMK1D, HAS2, STC1, and EFNB2) with embryo development to blastocyst. METHODS: Exploratory study at a private clinic. Eighteen advanced maternal age patients were enrolled (37.3 ± 4.0 years). Seventy-five cumuli were collected, whose oocytes resulted in either developmental arrest (N = 33) or blastocyst formation (N = 42). The noninvasive CC gene expression was combined with time-lapse morphokinetic parameters and, for blastocysts, with qPCR-based aneuploidy testing on trophectoderm biopsies...
February 1, 2019: Journal of Assisted Reproduction and Genetics
Lun Suo, Yu Xiao Zhou, Li Ling Jia, Hai Bo Wu, Jin Zheng, Qi Feng Lyu, Li Hua Sun, Han Sun, Yan Ping Kuang
There exist some patients who face recurrent total fertilization failure during assisted reproduction treatment, but the pathological mechanism underlying is elusive. Here, by using sc-RNA-seq method, the transcriptome profiles of ten abnormally fertilized zygotes were assessed, including five zygotes from one patient with recurrent Poly-PN zygotes, and five zygotes from a patient with pronuclear fusion failure. Four zygotes with three pronuclear (Tri-PN) were collected from four different patients as controls...
December 17, 2018: Scientific Reports
Imtiyaz Khanday, Debra Skinner, Bing Yang, Raphael Mercier, Venkatesan Sundaresan
The molecular pathways that trigger the initiation of embryogenesis after fertilization in flowering plants, and prevent its occurrence without fertilization, are not well understood1 . Here we show in rice (Oryza sativa) that BABY BOOM1 (BBM1), a member of the AP2 family2 of transcription factors that is expressed in sperm cells, has a key role in this process. Ectopic expression of BBM1 in the egg cell is sufficient for parthenogenesis, which indicates that a single wild-type gene can bypass the fertilization checkpoint in the female gamete...
December 12, 2018: Nature
Jacinta H Martin, R John Aitken, Elizabeth G Bromfield, Brett Nixon
BACKGROUND: DNA integrity and stability are critical determinants of cell viability. This is especially true in the female germline, wherein DNA integrity underpins successful conception, embryonic development, pregnancy and the production of healthy offspring. However, DNA is not inert; rather, it is subject to assault from various environment factors resulting in chemical modification and/or strand breakage. If structural alterations result and are left unrepaired, they have the potential to cause mutations and propagate disease...
December 12, 2018: Human Reproduction Update
Ömer Copur, Andrey Gorchakov, Katja Finkl, Mitzi I Kuroda, Jürg Müller
Acetylation of histone H4 at lysine 16 (H4K16) modulates nucleosome-nucleosome interactions and directly affects nucleosome binding by certain proteins. In Drosophila , H4K16 acetylation by the dosage compensation complex subunit Mof is linked to increased transcription of genes on the single X chromosome in males. Here, we analyzed Drosophila containing different H4K16 mutations or lacking Mof protein. An H4K16A mutation causes embryonic lethality in both sexes, whereas an H4K16R mutation permits females to develop into adults but causes lethality in males...
December 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Qian-Qian Sha, Jia-Li Yu, Jing-Xin Guo, Xing-Xing Dai, Jun-Chao Jiang, Yin-Li Zhang, Chao Yu, Shu-Yan Ji, Yu Jiang, Song-Ying Zhang, Li Shen, Xiang-Hong Ou, Heng-Yu Fan
Meiotic resumption-coupled degradation of maternal transcripts occurs during oocyte maturation in the absence of mRNA transcription. The CCR4-NOT complex has been identified as the main eukaryotic mRNA deadenylase. In vivo functional and mechanistic information regarding its multiple subunits remains insufficient. Cnot6l , one of four genes encoding CCR4-NOT catalytic subunits, is preferentially expressed in mouse oocytes. Genetic deletion of Cnot6l impaired deadenylation and degradation of a subset of maternal mRNAs during oocyte maturation...
December 14, 2018: EMBO Journal
L T M Vandenberghe, B Heindryckx, K Smits, M Popovic, K Szymanska, D Bonte, L Peelman, D Deforce, P De Sutter, A Van Soom, C De Schauwer
Platelet-activating factor (PAF) is a well-known marker for embryo quality and viability. For the first time, we describe an intracellular localisation of PAF in oocytes and embryos of cattle, mice and humans. We showed that PAF is represented in the nucleus, a signal that was lost upon nuclear envelope breakdown. This process was confirmed by treating the embryos with nocodazole, a spindle-disrupting agent that, as such, arrests the embryo in mitosis, and by microinjecting a PAF-specific antibody in bovine MII oocytes...
November 21, 2018: Reproduction, Fertility, and Development
Filip Horvat, Helena Fulka, Radek Jankele, Radek Malik, Ma Jun, Katerina Solcova, Radislav Sedlacek, Kristian Vlahovicek, Richard M Schultz, Petr Svoboda
Removal of poly(A) tail is an important mechanism controlling eukaryotic mRNA turnover. The major eukaryotic deadenylase complex CCR4-NOT contains two deadenylase components, CCR4 and CAF1, for which mammalian CCR4 is encoded by Cnot6 or Cnot6l paralogs. We show that Cnot6l apparently supplies the majority of CCR4 in the maternal CCR4-NOT in mouse, hamster, and bovine oocytes. Deletion of Cnot6l yielded viable mice, but Cnot6l -/- females exhibited ∼40% smaller litter size. The main onset of the phenotype was post-zygotic: fertilized Cnot6l -/- eggs developed slower and arrested more frequently than Cnot6l +/- eggs, suggesting that maternal CNOT6L is necessary for accurate oocyte-to-embryo transition...
August 2018: Life science alliance
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) is required for replication-dependent histone mRNA metabolism in mammals. Zebrafish possesses two slbps , and slbp1 is necessary for retinal neurogenesis. However, the detailed expression and function of slbp2 in zebrafish are still unknown. In this study, we first identified zebrafish slbp2 as an oocyte-specific maternal factor and then generated a maternal-zygotic slbp2 F3 homozygous mutant (MZ slbp2 Δ4-/- ) using CRISPR/Cas9. The depletion of maternal Slbp2 disrupted early nuclear cleavage, which resulted in developmental arrest at the MBT stage...
December 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
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