bims-mazytr Biomed News
on Maternal‐to‐zygotic transition
Issue of 2025–05–25
eight papers selected by
川一刀



  1. Commun Biol. 2025 May 21. 8(1): 769
      While protein aggregation is a well-documented factor in various age-related diseases, its specific impact on oocyte aging and the molecular mechanisms responsible remain poorly understood. In a mouse model of advanced maternal age, we observe that aging promotes ubiquitinated protein aggregation in oocytes and embryos. Starting with this clue, we identify that the expression of ubiquitin-conjugating enzyme (E2) UBE2V1 in oocyte increases with age and correlates with aggresome formation. We further provide evidence that UBE2V1 positively regulates protein aggregates formation in oocyte under both physiological and stress conditions. Moreover, enhanced UBE2V1 expression mimics the phenotypes observed in aged oocytes. Notably, restoring UBE2V1 expression in aged oocytes and embryos not only alleviates aggresome formation but also partly ameliorates the age-related defects in oocyte maturation and embryo development. Thus, our findings provide a mechanistic link between UBE2V1 expression, protein aggregation and developmental defects in aged oocytes and embryos.
    DOI:  https://doi.org/10.1038/s42003-025-08214-5
  2. Science. 2025 May 22. 388(6749): eads1234
      Following fertilization, the preimplantation embryo undergoes successive rounds of cell division and must accurately propagate the genetic material to ensure successful development. However, early mammalian embryos lack efficient spindle assembly mechanisms, and it remains unclear how error-free chromosome segregation is achieved. In this work, we imaged early mouse embryos and identified a network of nuclear actin cables that organize prophase chromosomes at the nuclear periphery. Following nuclear envelope breakdown, the network contracts and gathers chromosomes toward the cell center. Network contraction was driven by filament disassembly in a myosin II-independent manner. Additionally, we identified a network of branched actin filaments that attenuates metaphase spindle elongation. We also visualized nuclear actin in human embryos, suggesting a conserved role for actin in ensuring mitotic fidelity during early mammalian development.
    DOI:  https://doi.org/10.1126/science.ads1234
  3. Genome Med. 2025 May 19. 17(1): 57
       BACKGROUND: Three-dimensional (3D) chromatin architecture undergoes dynamic reorganization during mammalian gametogenesis and early embryogenesis. While mouse studies have shown species-specific patterns as well as mechanisms underlying de novo organization, these remain poorly characterized in humans. Although RNA polymerases II and III have been shown to regulate chromatin structure, the potential role of RNA polymerase I (Pol I), which drives ribosomal RNA production, in shaping 3D genome organization during these developmental transitions has not been investigated.
    METHODS: We employed a modified low-input in situ Hi-C approach to systematically compare 3D genome architecture dynamics from gametogenesis through early embryogenesis in human and mouse. Complementary Smart-seq2 for low-input transcriptomics, CUT&Tag for Pol I profiling, and Pol I functional inhibition assays were performed to elucidate the mechanisms governing chromatin organization.
    RESULTS: Our study revealed an extensive reorganization of the 3D genome from human oogenesis to early embryogenesis, displaying significant differences with the mouse, including dramatically attenuated topologically associating domains (TADs) at germinal vesicle (GV) stage oocytes. The 3D genome reconstruction timing is a fundamental difference between species. In human, reconstruction initiates at the 4-cell stage embryo in human, while in mouse, it commences at the 2-cell stage embryo. We discovered that Pol I is crucial for establishing the chromatin structures during mouse embryogenesis, but not in human embryos. Intriguingly, the absence of Pol I transcription weakens TAD structure in mouse female germline stem cells, whereas it fortifies it in human counterparts.
    CONCLUSIONS: These observed interspecies distinctions in chromatin organization dynamics provide novel insights into the evolutionary divergence of chromatin architecture regulation during early mammalian development. Our findings provide mechanistic insights into species-specific chromatin organization during germ cell and embryonic development and have potential implications for fertility preservation and birth defect prevention.
    Keywords:  Chromatin structure; Early embryonic development; Polymerase I; Stem cell
    DOI:  https://doi.org/10.1186/s13073-025-01476-y
  4. Curr Opin Genet Dev. 2025 May 20. pii: S0959-437X(25)00049-8. [Epub ahead of print]93 102357
      Stem cell-based embryo models have taken the scientific community by storm as they enable investigation of previously inaccessible stages of human development. Here, we discuss how stem cell-based embryo and placenta models can shine a light on two elusive and intertwined aspects of human development that are critical for successful pregnancy: the implantation of the blastocyst into the endometrium and the subsequent invasion of placental villi deep inside the maternal tissues. Both of these processes are mediated by the trophoblast lineage, which is specified in the preimplantation embryo and can be modeled using naïve pluripotent stem cells. We review how embryo and placenta models built from naïve stem cells can be leveraged to obtain mechanistic insights into human implantation and trophoblast invasion.
    DOI:  https://doi.org/10.1016/j.gde.2025.102357
  5. Methods Mol Biol. 2025 May 22.
      Recent advances in three-dimensional (3D) modeling of post-implantation human embryos using human pluripotent stem cells (hPSCs) have revolutionized our ability to investigate this crucial yet enigmatic stage of development. Here we detail the generation of the human extra-embryoid (hEE), a 3D stem cell-based embryo model that uniquely captures key spatiotemporal events of peri-gastrulation development through the formation and co-development of post-implantation embryonic and extra-embryonic lineages, with high efficiency and robustness across genetic backgrounds. This chapter provides a detailed protocol for generating hEEs in vitro, including guidance on hPSC maintenance, expected cell morphology, troubleshooting strategies, and key culture techniques.
    Keywords:  3D culture; Differentiation; Embryo model; Human embryo; Human embryonic stem cells; Human extra-embryoid; Pluripotency; Post-implantation; Stem cell
    DOI:  https://doi.org/10.1007/7651_2025_647
  6. Bio Protoc. 2025 Mar 20. 15(6): e5242
      Super-resolution imaging of RNA-protein (RNP) condensates has shown that most are composed of different immiscible phases reflected by a heterogenous distribution of their main components. Linking RNA-protein condensate's inner organization with their different functions in mRNA regulation remains a challenge, particularly in multicellular organisms. Drosophila germ granules are a model of RNA-protein condensates known for their role in mRNA storage and localized protein production in the early embryo. Present at the posterior pole of the embryo within a specialized cytoplasm called germplasm, they are composed of maternal mRNAs as well as four main proteins that play a key role in germ granule formation, maintenance, and function. Germ granules are necessary and sufficient to drive germ cell formation through translational regulation of maternal mRNAs such as nanos. Due to their localization at the posterior tip of the ovoid embryo and small size, the classical imaging setup does not provide enough resolution to reach their inner organization. Here, we present a specific mounting design that reduces the distance between the germ granule and the objectives. This method provides optimal resolution for the imaging of germ granules by super-resolution microscopy, allowing us to demonstrate their biphasic organization characterized by the enrichment of the four main proteins in the outermost part of the granule. Furthermore, combined with the direct visualization of nanos mRNA translation using the Suntag approach, this method enables the localization of translation events within the germ granule's inner organization and thus reveals the spatial organization of its functions. This approach reveals how germ granules serve simultaneously as mRNA storage hubs and sites of translation activation during development. This work also highlights the importance of considering condensates' inner organization when investigating their functions. Key features • Method for super-resolution imaging of germ granules in Drosophila early embryo. • Analysis of RNP condensate functional organization. • Simultaneous recording of RNP condensate function and organization.
    Keywords:  Drosophila; Embryogenesis; RNP condensates; STED microscopy; Suntag method; Translation
    DOI:  https://doi.org/10.21769/BioProtoc.5242
  7. Cell. 2025 May 15. pii: S0092-8674(25)00458-1. [Epub ahead of print]
      The amnion, an extra-embryonic tissue in mammalian embryos, is thought to provide crucial signaling, structural, and nutritional support during pregnancy. Despite its pivotal importance, studying human amnion formation and function has been hampered by the lack of accurate in vitro models. Here, we present an embryonic stem cell-derived 3D model of the post-gastrulation amnion, post-gastrulation amnioids (PGAs), that faithfully recapitulates extra-embryonic development up to 4 weeks post-fertilization, closely mimicking the functional traits of the human amniotic sac. PGAs self-organize, forming the amnion and the yolk sac, and are surrounded by the extra-embryonic mesoderm. Using PGAs, we show that GATA3 is required and sufficient for amniogenesis and that an autoregulatory feedback loop governs amnion formation, whereby extra-embryonic signals promote amnion specification. The reproducibility and scalability of the PGA system, with its precise cellular, structural, and functional integrity, opens avenues for investigating embryo-amnion interactions beyond gastrulation and offers an ideal platform for large-scale pharmacological and clinical studies.
    Keywords:  BMP4; GATA3; WNT; amnion; extra-embryonic tissues; hESCs; human development; self-organization; stem cell-based models of human development
    DOI:  https://doi.org/10.1016/j.cell.2025.04.025
  8. Front Endocrinol (Lausanne). 2025 ;16 1577702
      This review explores the non-invasive applications of Raman spectroscopy in assisted reproductive technology (ART). Raman spectroscopy, a powerful tool for analyzing biological samples, has shown great potential in enhancing ART outcomes through various applications such as sperm quality assessment, oocyte evaluation, and embryo selection. The non-destructive nature and high specificity of this technique enable detailed biochemical analysis at the cellular level, offering valuable insights into cellular processes without harming for the samples. The review highlights recent advancements and studies demonstrating the efficacy of Raman spectroscopy in improving the selection criteria for gametes and embryos, ultimately contributing to higher success rates in ART. Future perspectives on integrating Raman spectroscopy with other technologies to further enhance its applicability in reproductive medicine are also discussed.
    Keywords:  Raman spectroscopy; assisted reproductive technology (ART); embryo viability; gamete quality; non-invasive assessment
    DOI:  https://doi.org/10.3389/fendo.2025.1577702