bims-mazytr Biomed News
on Maternal‐to‐zygotic transition
Issue of 2025–06–15
ten papers selected by
川一刀
  1. Embryo and prejudice: From diverse first transcriptional impressions to a common developmental path.
  2. Nuclearporin subcomplex Nup98/Rae1 is vital for maternal-to-zygotic transition during early embryonic development.
  3. Tmx2 Maintains Mitochondrial Function to Support Preimplantation Embryogenesis.
  4. Bulk-level maps of pioneer factor binding dynamics during Drosophila maternal-to-zygotic transition.
  5. From genes to geometry: Controlling embryo models by programming genomic activation.
  6. Oviductin sets the species-specificity of the mammalian zona pellucida.
  7. Different populations of mouse egg cortical vesicles are responsible for post-fertilization zinc sparks and proteolysis of the zona pellucida.
  8. Impact of organelle architecture on oocyte developmental potential.
  9. Proteostasis in cellular dormancy: lessons from yeast to oocytes.
  10. Early signaling pathways during in vitro culture of isolated primordial follicles.
  1. Cell Genom. 2025 Jun 11. pii: S2666-979X(25)00175-2. [Epub ahead of print]5(6): 100919
    Embryo and prejudice: From diverse first transcriptional impressions to a common developmental path.
    Guillaume Giraud Collet, Nicola Festuccia, Pablo Navarro.
      Pre-implantation mammalian development culminates in the blastocyst, where embryonic and extra-embryonic tissue founders reside. However, species variations in the underlying mechanisms, starting from zygotic genome activation (ZGA), remain underexplored. In this issue of Cell Genomics, Zhang et al.1 studied RNA Pol II in bovine embryos and discovered super RNA Pol II domains, a regulatory architecture promoting transcription in species with delayed ZGA.
    DOI:  https://doi.org/10.1016/j.xgen.2025.100919
  2. Theriogenology. 2025 Jun 05. pii: S0093-691X(25)00245-6. [Epub ahead of print]245 117519
    Nuclearporin subcomplex Nup98/Rae1 is vital for maternal-to-zygotic transition during early embryonic development.
    Luo Anfeng, Gu Hao, Akhtar Ali, Qi Mengfan, Pan Kaixin, Zhou Changfan, Zeng Wei, Liu Song, Ren Hongyan, Bi Yanzhen, Chen Fan.
      The Nup98/Rae1 nuclear pore subcomplex, a critical mediator of nucleocytoplasmic transport, orchestrates fundamental cellular processes including transcriptional regulation, mRNA surveillance, and mitotic fidelity. However, its functional significance during early embryogenesis remains incompletely understood. In this study, we employed an in vitro embryo culture system combined with embryo electroporation-mediated interference to investigate the role of Nup98/Rae1 in early mouse embryos. Our results revealed that Nup98/Rae1 deficiency led to delayed embryonic progression and a significant decline in blastocyst formation rates. Transcriptomic analysis using SMART-seq2 in two-cell stage embryos revealed that Nup98/Rae1 modulates global gene expression, particularly within pathways governing RNA splicing, protein catabolism, and the DNA damage response. Integration of transcriptomic data with established databases further confirmed that Nup98/Rae1 is indispensable for zygotic genome activation and maternal mRNA clearance-key events in the maternal-to-zygotic transition. Moreover, quantitative immunofluorescence analysis demonstrated that loss of Nup98/Rae1 resulted in heightened DNA damage and reduced H3K27ac levels. Additionally, the increased mRNA expression of apoptosis-related markers BAX and CASPASE3, alongside positive TUNEL staining, indicated the induction of early apoptosis. Immunostaining for Sox2 and Cdx2 revealed a defective inner cell mass development, highlighting the detrimental impact of Nup98/Rae1 on cell fate specification. Collectively, these findings indicate that Nup98/Rae1 deficiency disrupts maternal mRNA degradation, impairs zygotic genome activation, alters histone modifications, induces genomic instability, and ultimately compromises early embryonic development by triggering apoptosis.
    Keywords:  Early embryonic development; Histone modification; Nup98; Rae1; Zygotic genome activation
    DOI:  https://doi.org/10.1016/j.theriogenology.2025.117519
  3. FASEB J. 2025 Jun 15. 39(11): e70723
    Tmx2 Maintains Mitochondrial Function to Support Preimplantation Embryogenesis.
    Shangrong Zhang, Qing Liu, Siyu Wang, Xiaoyu Zhang, Dingmei Qin, Ruisong Bai, Ji Chen, Zijian Ma, Zhipeng Lin, Yuheng Bi, Huan Liu, Aoxue Sun, Zhongzhi Mo, Hongcheng Wang, Xiaoqing Wu, Yong Liu.
      Thioredoxin (TRX)-related transmembrane proteins (TMX), a subgroup of the protein disulfide isomerase (PDI) family, comprise a class of transmembrane proteins with diverse biological functions. Among these, TMX2 (PDIA12) remains one of the least characterized members. Recent studies have identified missense mutations in TMX2 associated with aberrant brain development and cerebellar malformations, highlighting its potential importance in developmental processes. Notably, Tmx2 mutant embryos exhibit developmental arrest at the E3.5 stage, suggesting a critical role in preimplantation embryogenesis. However, the precise molecular and cellular functions of Tmx2 in mammalian embryonic development remain largely unexplored. In this study, we provide novel insights into the essential role of Tmx2 during preimplantation embryonic development in mice. We demonstrate that TMX2 is specifically expressed in mouse embryos, with its subcellular localization closely associated with mitochondria during the two-cell to eight-cell stages. Knockdown of Tmx2 recapitulates the phenotypic defects observed in genetic mutants, revealing a pronounced impairment in blastomere proliferation, as confirmed by EdU incorporation assays. Furthermore, TUNEL assays indicate a significant increase in apoptotic signaling in Tmx2-deficient embryos, accompanied by elevated mRNA levels of the cell cycle inhibitors p21 and p53. Mechanistically, we show that Tmx2 knockdown disrupts mitochondrial function, leading to oxidative stress and impaired mitophagy and autophagy in developing embryos. These findings suggest that Tmx2 plays a pivotal role in maintaining mitochondrial integrity and cellular homeostasis during preimplantation embryogenesis. In summary, our study elucidates the critical role of Tmx2 in preimplantation embryonic development in mice, primarily through its regulation of mitochondrial function. These results advance our understanding of the molecular mechanisms governing preimplantation embryonic development and establish Tmx2 as a key regulator of mitochondrial dynamics and cellular survival during this critical developmental window.
    Keywords:   Tmx2 ; autophagy; embryo development; mice; mitochondrial dysfunction
    DOI:  https://doi.org/10.1096/fj.202500640R
  4. Development. 2025 Jun 13. pii: dev.204460. [Epub ahead of print]
    Bulk-level maps of pioneer factor binding dynamics during Drosophila maternal-to-zygotic transition.
    Sadia Siddika Dima, Gregory T Reeves.
      Gene regulation by transcription factors (TFs) binding cognate sequences is of paramount importance. For example, the TFs Zelda (Zld) and GAGA factor (GAF) are widely acknowledged for pioneering gene activation during zygotic genome activation (ZGA) in Drosophila. However, quantitative dose/response relationships between bulk TF concentration and DNA binding, an event tied to transcriptional activity, remain elusive. Here, we map these relationships during ZGA: a crucial step in metazoan development. To map the dose/response relationship between nuclear concentration and DNA binding, we performed raster image correlation spectroscopy, a method that can measure biophysical parameters of fluorescent molecules. We found that, although Zld concentration increases during nuclear cycles (ncs) 10 to 14, its binding in the transcriptionally active regions decreases, consistent with its function as an activator for early genes. In contrast, GAF-DNA binding is nearly linear with its concentration, which sharply increases during the major wave, implicating it in the major wave. This study provides key insights into the properties of the two factors and puts forward a quantitative approach that can be used for other TFs to study transcriptional regulation.
    Keywords:  DNA binding; GAGA factor; Pioneer factors; Raster image correlation spectroscopy; Zelda; Zygotic genome activation
    DOI:  https://doi.org/10.1242/dev.204460
  5. Cell Stem Cell. 2025 Jun 05. pii: S1934-5909(25)00180-8. [Epub ahead of print]32(6): 857-858
    From genes to geometry: Controlling embryo models by programming genomic activation.
    Harold M McNamara, Berna Sozen.
      Embryo-like models derived from stem cells have emerged as powerful tools to study early development. In this issue, Lodewijk et al.1 demonstrate that activating just two enhancers via CRISPR activation (CRISPRa) in mouse embryonic stem cells (ESCs) can drive self-organization into structured embryo-like models, offering a genome-driven approach in stem cell and developmental biology.
    DOI:  https://doi.org/10.1016/j.stem.2025.04.013
  6. Elife. 2025 Jun 09. pii: RP101338. [Epub ahead of print]13
    Oviductin sets the species-specificity of the mammalian zona pellucida.
    Daniel de la Fuente, Maria Maroto, Yulia N Cajas, Karina Canon-Beltran, Raul Fernandez-Gonzalez, Ana Munoz-Maceda, Juana M Sanchez-Puig, Rafael Blasco, Paula Cots-Rodríguez, Manuel Avilés, Dimitrios Rizos, Alfonso Gutierrez-Adan.
      The zona pellucida (ZP) is vital for species-specific fertilization as this barrier mediates sperm-oocyte binding. Here, we determined whether sperm from distant mammalian orders (Carnivora, Primates, and Rodentia) could penetrate bovine oocytes by examining the role of bovine oviductal fluid and species-specific oviductal glycoprotein (OVGP1 or oviductin) from bovine, murine, or human sources in modulating the species-specificity of bovine and murine oocytes. Sperm from all the species were found to penetrate intact bovine ovarian oocytes to form hybrid embryos. However, contact with oviductal fluid or bovine, murine, or human OVGP1, conferred the ZP species-specificity, allowing only the penetration of the corresponding sperm regardless of the ZP's origin. Glycolytic and microstructural analyses revealed that OVGP1 covers the pores present in the ZP and that OVGP1 glycosylation determines sperm specificity. This suggests specific fertilization capacity is acquired in the oviduct through the ZP's incorporation of specific oviductin.
    Keywords:  OVGP1; bovine; developmental biology; fertilization; human; mouse; zona pellucida
    DOI:  https://doi.org/10.7554/eLife.101338
  7. iScience. 2025 Jun 20. 28(6): 112606
    Different populations of mouse egg cortical vesicles are responsible for post-fertilization zinc sparks and proteolysis of the zona pellucida.
    Omar José, Boris Baibakov, Jurrien Dean.
      Fertilization of mouse eggs by sperm triggers exocytosis of cortical granules, releasing zinc sparks as well as ovastacin that cleaves ZP2 in the zona pellucida. The mechanism by which zinc accumulates in cortical granules prior to fertilization has yet to be determined. We microinjected cRNAs encoding eight zinc transporters (ZnTs) into mouse oocytes and observed that only ZnT2 and ZnT4 accumulate in structures located in the cortex. We genetically ablated the single-copy genes encoding each of the two transporters. The absence of both transporters in ovulated eggs impaired accumulation of zinc in cortical granules and release of zinc sparks. Ovastacin and zinc are present in mostly non-overlapping populations of cortical granules. Our results provide new insights into the biology of mammalian cortical granules, but the release of zinc sparks does not affect the post-fertilization number of sperm in the perivitelline space nor increases polyspermy.
    Keywords:  Developmental biology; cell biology
    DOI:  https://doi.org/10.1016/j.isci.2025.112606
  8. Curr Opin Cell Biol. 2025 Jun 11. pii: S0955-0674(25)00094-8. [Epub ahead of print]95 102556
    Impact of organelle architecture on oocyte developmental potential.
    Elvira Nikalayevich, Noemi Zollo, Marie-Hélène Verlhac.
      Oocytes are female gametes specialized in storing maternal RNAs, proteins, lipids, and metabolites essential for embryonic development after fertilization, sometimes for decades in humans. To support this extended lifespan, oocytes have evolved mechanisms to organize specialized organelles. This review highlights recent discoveries on how oocytes regulate mRNA and protein accumulation, storage, and degradation over time. Additionally, we explore advances in understanding cytoplasmic activity and remodeling, particularly the role of cortex mechanical properties in fine-tuning organelle distribution and function to ensure proper oocyte development.
    DOI:  https://doi.org/10.1016/j.ceb.2025.102556
  9. Trends Biochem Sci. 2025 Jun 11. pii: S0968-0004(25)00108-2. [Epub ahead of print]
    Proteostasis in cellular dormancy: lessons from yeast to oocytes.
    Stephanie Rosswag de Souza, Elvan Böke, Gabriele Zaffagnini.
      Cellular dormancy is characterized by a prolonged, reversible cell cycle arrest and absence of growth. Dormancy allows organisms to endure unfavorable environmental conditions and to maintain long-lived quiescent progenitor cells essential for tissue homeostasis and reproduction. Protein homeostasis (proteostasis) is central to the maintenance of intracellular integrity in all cell types, particularly in long-lived, non-dividing cells. Here we review adaptations to support proteostasis in dormant cells and highlight common themes of cellular dormancy across organisms, from yeast to adult quiescent stem cells. We also feature vertebrate oocytes as an emerging model of proteostasis during dormancy. Together, these comparisons reveal common and unique strategies to sustain proteostasis during dormancy, offering insights into how cells preserve function and viability over long quiescence periods.
    Keywords:  mTOR; protein aggregates; protein degradation; quiescence; ribosome biogenesis; translation
    DOI:  https://doi.org/10.1016/j.tibs.2025.05.004
  10. Mol Hum Reprod. 2025 Jun 09. pii: gaaf026. [Epub ahead of print]
    Early signaling pathways during in vitro culture of isolated primordial follicles.
    Pritha Dey, Noemi Monferini, Ludovica Donadini, Filippo Zambelli, Maria Belen Rabaglino, Valentina Lodde, Federica Franciosi, Alberto Maria Luciano.
      The ability to grow undifferentiated oocytes in vitro from primordial follicles would increase the availability of fully grown oocytes in fertility preservation programs and other downstream applications. To date, the development of living offspring in vitro from the primordial follicle reserve has only been achieved in mice, proving the principle of the potential value of follicle culture as a source of competent oocytes. In certain pathophysiological conditions, such as polycystic ovarian syndrome, premature ovarian failure, or ovarian and blood cancer, where the ovarian tissue cannot be reintroduced into the patient, it is essential to isolate these follicles from the surrounding tissue and culture them in vitro. However, the culture systems that produce mature oocytes from isolated primordial follicles are still under investigation. Upon isolation from the ovarian microenvironment, a critical limiting factor is follicle death after a short period of culture. Previous studies suggest that glycine, a key component of glutathione (GSH), plays a protective role against the programmed cell death mechanism, ferroptosis, in in vitro matured porcine oocytes via the System Xc-/GSH/glutathione peroxidase 4 (GPX4) axis. Employing a previously developed high-yielding primordial follicle mechanical isolation strategy and a defined culture system, we used RNA-seq to advance the knowledge of the main transcriptional events and molecular factors determining follicle fate in a 2D culture system. Our transcriptome analyses identified genes involved in ferroptosis that may bring about primordial follicle death. To suppress ferroptosis, glycine supplementation maintained the viability of primordial follicles at approximately 85% for 16 hours. Future improvements to the culture system should inhibit programmed cell death mechanisms and ensure the physiological compliance of the genes regulating primordial follicle activation and transition to the primary stage, along with effective supplementation media to develop isolated primordial follicles in vitro.
    Keywords:   In vitro Culture; Bovine; Ferroptosis; Folliculogenesis; Glycine; Mechanical Isolation; Ovarian Reserve; Primordial Follicle; Programmed cell death; RNA-seq
    DOI:  https://doi.org/10.1093/molehr/gaaf026
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