bims-mazytr Biomed News
on Maternal‐to‐zygotic transition
Issue of 2025–04–13
eleven papers selected by
川一刀
  1. Reshaping transcription and translation dynamics during the awakening of the zygotic genome.
  2. Perturbing nuclear glycosylation in the mouse preimplantation embryo slows down embryonic development.
  3. Single-cell 5-hydroxymethylcytosine landscapes of mouse early embryos at single-base resolution.
  4. DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity.
  5. Suppression of oocyte glycine transporter activity in mouse cumulus-oocyte complexes before resumption of meiosis†.
  6. Sperm derived H2AK119ub1 is required for embryonic development in Xenopus laevis.
  7. The guinea pig serves as an alternative model to study human preimplantation development.
  8. The cohesin-associated protein Pds5A governs the meiotic spindle assembly via deubiquitination of Kif5B in oocytes.
  9. Prolonged metaphase II arrest weakens Aurora B/C-dependent error correction in mouse oocytes.
  10. Sperm morphology of the Australasian hydromyine rodents and the interactions between the spermatozoon and oocyte at the time of fertilisation.
  11. The regulation and function of post-transcriptional RNA splicing.
  1. Curr Opin Genet Dev. 2025 Apr 04. pii: S0959-437X(25)00036-X. [Epub ahead of print]92 102344
    Reshaping transcription and translation dynamics during the awakening of the zygotic genome.
    Louise Maillard, Pierre Bensidoun, Mounia Lagha.
      During the oocyte-to-embryo transition, the transcriptome and proteome are dramatically reshaped. This transition entails a shift from maternally inherited mRNAs to newly synthesized transcripts, produced during the zygotic genome activation (ZGA). Furthermore, a crucial transcription and translation selectivity is required for early embryonic development. Studies across various model organisms have revealed conserved cis- and trans-regulatory mechanisms dictating the regimes by which mRNA and proteins are produced during this critical phase. In this article, we highlight recent technological and conceptual advances that deepen our understanding of how the tuning of both transcription and translation evolves during ZGA.
    DOI:  https://doi.org/10.1016/j.gde.2025.102344
  2. Proc Natl Acad Sci U S A. 2025 Apr 15. 122(15): e2410520122
    Perturbing nuclear glycosylation in the mouse preimplantation embryo slows down embryonic development.
    Sara Formichetti, Joana B Serrano, Urvashi Chitnavis, Agnieszka Sadowska, Na Liu, Ana Boskovic, Matthieu Boulard.
      The main form of intracellular protein glycosylation (O-GlcNAc) is reversible and has been mapped on thousands of cytoplasmic and nuclear proteins, including RNA polymerase II, transcription factors, and chromatin modifiers. The O-GlcNAc modification is catalyzed by a single enzyme known as O-GlcNAc Transferase, that is required for mammalian early development. Yet, neither the regulatory function of protein O-GlcNAcylation in the embryo nor the embryonic O-GlcNAc proteome have been documented. Here, we devised a strategy to enzymatically remove O-GlcNAc from preimplantation embryonic nuclei, where this modification accumulates coincidently with embryonic genome activation (EGA). Unexpectedly, the depletion of nuclear O-GlcNAc to undetectable levels has no impact on EGA, but dampens the transcriptional upregulation of the translational machinery, and triggers a spindle checkpoint response. These molecular alterations were phenotypically associated with a developmental delay starting from early cleavage stages and persisting after embryo implantation, establishing a link between nuclear glycosylation and the pace of embryonic development.
    Keywords:  O-GlcNAc; embryonic genome activation; gene expression; preimplantation development
    DOI:  https://doi.org/10.1073/pnas.2410520122
  3. Cell Rep. 2025 Apr 03. pii: S2211-1247(25)00291-8. [Epub ahead of print]44(4): 115520
    Single-cell 5-hydroxymethylcytosine landscapes of mouse early embryos at single-base resolution.
    Dongsheng Bai, Jinmin Yang, Xiaohui Xue, Yun Gao, Yan Wang, Mengge Cui, Bo He, Hu Zeng, Huifen Xiang, Zijian Guo, Lan Zhu, Juan Gao, Chenxu Zhu, Fuchou Tang, Chengqi Yi.
      DNA methylation and hydroxymethylation are extensively reprogrammed during mammalian early embryogenesis, and studying their regulatory functions requires comprehensive DNA hydroxymethylation maps at base resolution. Here, we develop single-cell 5-hydroxymethylcytosine (5hmC) chemical-assisted C-to-T conversion-enabled sequencing (schmC-CATCH), a method leveraging selective 5hmC labeling for a quantitative, base-resolution, genome-wide landscape of the DNA hydroxymethylome in mouse gametes and preimplantation embryos spanning from the zygote to blastocyst stage. We revealed that, in addition to late zygotic stages, onset of ten-eleven translocation (TET)-mediated DNA hydroxymethylation initiates immediately after fertilization and is characterized by the distinct 5hmC patterns on the parental genomes shaped by TET3 demethylase. We identified persistent clusters of 5hmC hotspots throughout early embryonic stages, which are highly associated with young retroelements. 5hmC is also associated with different regulatory elements, indicating a potential regulatory function during early embryogenesis. Collectively, our work elucidates the dynamics of active DNA demethylation during mouse preimplantation development and provides a valuable resource for functional studies of epigenetic reprogramming in early embryos.
    Keywords:  CP: Developmental biology; CP: Molecular biology; DNA hydroxymethylation; TET3; bisulfite-free method; mammalian early embryo; single cell sequencing
    DOI:  https://doi.org/10.1016/j.celrep.2025.115520
  4. Cell Rep. 2025 Apr 08. pii: S2211-1247(25)00315-8. [Epub ahead of print]44(4): 115544
    DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity.
    Lieying Xiao, Hao Jin, Yanna Dang, Panpan Zhao, Shuang Li, Yan Shi, Shaohua Wang, Kun Zhang.
      Maternal-deposited factors initiate zygotic genome activation (ZGA), driving the maternal-to-zygotic transition; however, the coordination between maternal coactivators and transcription factors (TFs) in this process remains unclear. In this study, by profiling the dynamic landscape of p300 during mouse ZGA, we reveal its role in promoting RNA polymerase II (Pol II) pre-configuration at ZGA gene regions and sequentially establishing enhancer activity and regulatory networks. Moreover, p300/CBP-catalyzed acetylation drives Pol II elongation and minor ZGA gene expression by inducing pivotal TFs such as Dux. Remarkably, the supplementation of exogenous Dux rescues ZGA failure and developmental defects caused by the loss of p300/CBP acetylation. DUX functions as a pioneer factor, guiding p300 and Pol II to minor ZGA gene regions and activating them in a manner dependent on the non-catalytic functions of p300/CBP. Together, our findings reveal a mutual dependency between p300/CBP and DUX, highlighting their coordinated role in regulating minor ZGA activation.
    Keywords:  CP: Developmental biology; DUX; RNA polymerase II; ZGA; acetylation; embryo; enhancer; minor ZGA; p300/CBP; preimplantation
    DOI:  https://doi.org/10.1016/j.celrep.2025.115544
  5. Biol Reprod. 2025 Apr 09. pii: ioaf080. [Epub ahead of print]
    Suppression of oocyte glycine transporter activity in mouse cumulus-oocyte complexes before resumption of meiosis†.
    Allison K Tscherner, Jay M Baltz.
      Glycine is a key regulator of cell volume in early preimplantation mouse embryos and supports embryo viability. Its accumulation is initiated when the GLYT1 glycine transporter (SLC6A9) is activated in oocytes at about the same time the oocyte is released from meiotic arrest at the germinal vesicle (GV) stage. The mechanism by which GLYT1 is maintained in an inactive state before ovulation is triggered is unknown. Here, we have shown that GLYT1 activity can remain suppressed in isolated cumulus oocyte complexes (COCs) under defined culture conditions that include keeping COCs physically separated and using the physiological mediator of GV arrest, Natriuretic Peptide Precursor C (NPPC). When GV arrest is instead maintained in oocytes within COCs by inhibiting phosphodiesterase 3A (PDE3A) or cyclin-dependent kinase 1 (CDK1), GLYT1 similarly remains inactive. However, GLYT1 becomes activated in isolated GV oocytes similarly maintained in GV arrest, indicating that cumulus cells are required for suppressing GLYT1 activity. This implied that meiotic arrest was necessary but not sufficient for preventing GLYT1 activation and that an inhibitory factor likely arising from the cumulus was also required. Finally, we found that pyrrophenone, a selective inhibitor of arachidonic acid production by cytoplasmic phospholipase A alpha (cPLAα), caused GLYT1 to become activated in oocytes within COCs despite maintenance of meiotic arrest of the oocyte. Since arachidonic acid levels decrease in oocytes after release from GV arrest, we propose that arachidonic acid may be a candidate for the inhibitory factor in COCs that regulates GLYT1 activity.
    Keywords:  Arachidonic acid; cell volume regulation; cumulus; glycine; meiosis; oocyte
    DOI:  https://doi.org/10.1093/biolre/ioaf080
  6. Nat Commun. 2025 Apr 05. 16(1): 3268
    Sperm derived H2AK119ub1 is required for embryonic development in Xenopus laevis.
    Valentin Francois-Campion, Florian Berger, Mami Oikawa, Maissa Goumeidane, Nolwenn Mouniée, Vanessa Chenouard, Kseniya Petrova, Jose G Abreu, Cynthia Fourgeux, Jeremie Poschmann, Leonid Peshkin, Romain Gibeaux, Jérôme Jullien.
      Ubiquitylation of H2A (H2AK119ub1) by the polycomb repressive complexe-1 plays a key role in the initiation of facultative heterochromatin formation in somatic cells. Here we evaluate the contribution of sperm derived H2AK119ub1 to embryo development. In Xenopus laevis we found that H2AK119ub1 is present during spermiogenesis and into early embryonic development, highlighting its credential for a role in the transmission of epigenetic information from the sperm to the embryo. In vitro treatment of sperm with USP21, a H2AK119ub1 deubiquitylase, just prior to injection to egg, results in developmental defects associated with gene upregulation. Sperm H2AK119ub1 editing disrupts egg factor mediated paternal chromatin remodelling processes. It leads to post-replication accumulation of H2AK119ub1 on repeat element of the genome instead of CpG islands. This shift in post-replication H2AK119ub1 distribution triggered by sperm epigenome editing entails a loss of H2AK119ub1 from genes misregulated in embryos derived from USP21 treated sperm. We conclude that sperm derived H2AK119ub1 instructs egg factor mediated epigenetic remodelling of paternal chromatin and is required for embryonic development.
    DOI:  https://doi.org/10.1038/s41467-025-58615-7
  7. Nat Cell Biol. 2025 Apr;27(4): 696-710
    The guinea pig serves as an alternative model to study human preimplantation development.
    Jesica Romina Canizo, Cheng Zhao, Sophie Petropoulos.
      Preimplantation development is an important window of human embryogenesis. However, ethical constraints and the limitations involved in studying human embryos often necessitate the use of alternative model systems. Here we identify the guinea pig as a promising small animal model to study human preimplantation development. Using single-cell RNA-sequencing, we generated an atlas of guinea pig preimplantation development, revealing its close resemblance to early human embryogenesis in terms of the timing of compaction, early-, mid- and late-blastocyst formation, and implantation, and the spatio-temporal expression of key lineage markers. We also show conserved roles of Hippo, MEK-ERK and JAK-STAT signalling. Furthermore, multi-species analysis highlights the spatio-temporal expression of conserved and divergent genes during preimplantation development and pluripotency. The guinea pig serves as a valuable animal model for advancing preimplantation development and stem cell research, and can be leveraged to better understand the longer-term impact of early exposures on offspring outcomes.
    DOI:  https://doi.org/10.1038/s41556-025-01642-9
  8. Sci Adv. 2025 Apr 11. 11(15): eadt6159
    The cohesin-associated protein Pds5A governs the meiotic spindle assembly via deubiquitination of Kif5B in oocytes.
    Yu Zhang, Jie Bai, Bo Xiong.
      Chromosome cohesion mediated by cohesin complex and its associated proteins is required for accurate chromosome segregation and genomic stability in mitosis. However, because of the distinct operation mechanisms, many proteins might exert different functions during meiosis in germ cells. Here, we document that cohesin-associated protein precocious dissociation of sisters 5A (Pds5A) plays a noncanonical role in the meiotic spindle assembly during oocyte maturation independent of its cohesion function. Pds5A distributes on the spindle fibers in oocytes at both metaphase I and metaphase II stages. Morpholino-based depletion or genetic ablation of Pds5A all lead to defects in spindle organization, chromosome euploidy and meiotic progression in oocytes and thus compromising the female fertility. Mechanistically, Pds5A recruits deubiquitinase ubiquitin-specific protease 14 to the spindle apparatus for stabilization of kinesin family member 5B, regulating the spindle elongation. Collectively, our findings unveil that cohesin-associated protein Pds5A can be used as a spindle regulator during oocyte meiosis.
    DOI:  https://doi.org/10.1126/sciadv.adt6159
  9. Curr Biol. 2025 Apr 04. pii: S0960-9822(25)00315-X. [Epub ahead of print]
    Prolonged metaphase II arrest weakens Aurora B/C-dependent error correction in mouse oocytes.
    Antoine Langeoire, Alison Kem-Seng, Damien Cladière, Katja Wassmann, Eulalie Buffin.
      Chromosome segregation during meiosis is highly error-prone in mammalian oocytes. The mechanisms controlling chromosome attachments and the spindle assembly checkpoint (SAC) have been extensively studied in meiosis I, but our knowledge of these mechanisms during meiosis II is rather limited. Although mammalian oocytes arrest in metaphase II for an extended period awaiting fertilization, some misattached chromosomes may persist. This suggests that the mechanism correcting misattachments is not fully functional during the arrest. In this study, we investigated whether low inter-kinetochore tension, which characterizes incorrect attachments, can be detected by Aurora B/C-dependent error correction in meiosis II. We found that low tension, induced by low dose of STLC in early metaphase II, does indeed mediate microtubule detachment by Aurora B/C and, consequently, anaphase II delay through SAC activation. Surprisingly, we also found that, during prolonged metaphase II arrest, Aurora B/C activity is no longer sufficient to detach low-tension attachments, correlating with high accumulation of PP2A at kinetochores. As a result, the SAC is not activated, and sister chromatids segregate in anaphase II without delay even in the presence of low tension. Hence, during the prolonged metaphase II arrest to await fertilization, oocytes become unable to discriminate between correct and incorrect attachments and may allow errors to persist.
    Keywords:  Aurora B/C; SAC; error correction; meiosis; oocyte; spindle; tension
    DOI:  https://doi.org/10.1016/j.cub.2025.03.030
  10. Reprod Fertil Dev. 2025 Apr;pii: RD25012. [Epub ahead of print]37
    Sperm morphology of the Australasian hydromyine rodents and the interactions between the spermatozoon and oocyte at the time of fertilisation.
    William G Breed, Chris M Leigh, Emily Roycroft, Ingrid Ahmer.
      Context This paper explores the morphology of spermatozoa in Australian hydromyine rodents, specifically focusing on the plains mouse (Pseudomys australis ), and examines the interactions between sperm and eggs at time of fertilisation. Aims The aim of this study is to provide an overview of sperm morphology of hydromyine rodents, comparing its morphology across the different species and to investigate the interactions between the gametes at fertilisation in the plains mouse. Methods We summarise the sperm head morphology of the hydromyine rodents across the six divisions, with emphasis on the structure in the plains mouse and its interactions with the zona pellucida during fertilisation. Key results Most hydromyine rodents, including the plains mouse, exhibit a highly complex sperm head morphology with two prominent ventral processes in addition to the apical hook. These processes primarily contain filamentous actin with some species of the New Guinea Pogonomys Division having a nuclear extension into the lower process. Nevertheless three species in the Pogonomys Division and a few in the Pseudomys Division have derived sperm heads which lack the ventral processes which in the plains mouse bind the sperm to the zona pellucida around the ovulated oocyte. This may stabilise the sperm head at this time and facilitate zona pellucida penetration and fusion with the oolemma at this time. Conclusion The complex sperm head morphology in most of the hydromyine rodents is likely to date back over one million years with, in the plains mouse, interaction between sperm and egg during fertilisation involving sperm head stabilisation and zona pellucida attachment. Implications These findings suggest in hydromyine rodents valuable insights into the evolutionary development of sperm morphology and sperm-egg interactions during fertilisation, and in particular that the role of the ventral processes may be critical for successful fertilisation in this group. Understanding these processes could give insight into broader studies on reproductive strategies and evolutionary biology in rodents.
    DOI:  https://doi.org/10.1071/RD25012
  11. Nat Rev Genet. 2025 Apr 11.
    The regulation and function of post-transcriptional RNA splicing.
    Karine Choquet, Ines L Patop, L Stirling Churchman.
      Eukaryotic RNA transcripts undergo extensive processing before becoming functional messenger RNAs, with splicing being a critical and highly regulated step that occurs both co-transcriptionally and post-transcriptionally. Recent analyses have revealed, with unprecedented spatial and temporal resolution, that up to 40% of mammalian introns are retained after transcription termination and are subsequently removed largely while transcripts remain chromatin-associated. Post-transcriptional splicing has emerged as a key layer of gene expression regulation during development, stress response and disease progression. The control of post-transcriptional splicing regulates protein production through delayed splicing and nuclear export, or nuclear retention and degradation of specific transcript isoforms. Here, we review current methodologies for detecting post-transcriptional splicing, discuss the mechanisms controlling the timing of splicing and examine how this temporal regulation affects gene expression programmes in healthy cells and in disease states.
    DOI:  https://doi.org/10.1038/s41576-025-00836-z
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