bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–05–25
ten papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Actin organizes chromosomes and microtubules to ensure mitotic fidelity in the preimplantation embryo.
  2. Sequence diversity lost in early pregnancy.
  3. Population size interacts with reproductive longevity to shape the germline mutation rate.
  4. UBE2V1 governs aging induced protein aggregation and developmental defects in oocytes and embryos.
  5. Visualization of mRNA Translation Within Germ Granule Biphasic Organization in Drosophila Early Embryo.
  6. Non-homologous sequence interactions during meiosis: meiotic challenges and evolutionary opportunities.
  7. RNA polymerase I is essential for driving the formation of 3D genome in early embryonic development in mouse, but not in human.
  8. RNA-binding proteins DND1 and NANOS3 cooperatively suppress the entry of germ cell lineage.
  9. Dynamic SAS-6 phosphorylation aids centrosome duplication and elimination in C. elegans oogenesis.
  10. Molecular insights into RNA recognition by the ZAR1 C-terminal domain.
  1. Science. 2025 May 22. 388(6749): eads1234
    Actin organizes chromosomes and microtubules to ensure mitotic fidelity in the preimplantation embryo.
    Blake Hernandez, Piotr Tetlak, Ana Domingo-Muelas, Hiroki Akizawa, Robin M Skory, Goli Ardestani, Mate Biro, Xiaolei Liu, Stephanie Bissiere, Denny Sakkas, Nicolas Plachta.
      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
  2. Nature. 2025 May 21.
    Sequence diversity lost in early pregnancy.
    COPL Consortium
      Every generation, the human genome is shuffled during meiosis and a single fertilized egg gives rise to all of the cells of the body1. Meiotic errors leading to chromosomal abnormalities are known causes of pregnancy loss2,3, but genetic aetiologies of euploid pregnancy loss remain largely unexplained4. Here we characterize sequence diversity in early pregnancy loss through whole-genome sequencing of 1,007 fetal samples and 934 parental samples from 467 trios affected by pregnancy loss (fetus, mother and father). Sequenced parental genomes enabled us to determine both the parental and meiotic origins of chromosomal abnormalities, detected in half of our set. It further enabled us to assess de novo mutations on both homologous chromosomes from parents transmitting extra chromosomes, and date them, revealing that 6.6% of maternal mutations occurred before sister chromatid formation in fetal oocytes. We find a similar number of de novo mutations in the trios affected by pregnancy loss as in 9,651 adult trios, but three times the number of pathogenic small (<50 bp) sequence variant genotypes in the loss cases compared with adults. Overall, our findings indicate that around 1 in 136 pregnancies is lost due to a pathogenic small sequence variant genotype in the fetus. Our results highlight the vast sequence diversity that is lost in early pregnancy.
    DOI:  https://doi.org/10.1038/s41586-025-09031-w
  3. Proc Natl Acad Sci U S A. 2025 May 27. 122(21): e2423311122
    Population size interacts with reproductive longevity to shape the germline mutation rate.
    Luke Zhu, Annabel Beichman, Kelley Harris.
      Mutation rates vary across the tree of life by many orders of magnitude, with fewer mutations occurring each generation in species that reproduce quickly and maintain large effective population sizes. A compelling explanation is that large effective population sizes facilitate selection against weakly deleterious "mutator alleles" such as variants that modulate cell division or interfere with the molecular efficacy of DNA repair. However, while the fidelity of a single cell division largely determines microorganisms' mutation rates, the relationship of the mutation rate to the molecular determinants of DNA damage and repair is more complex in multicellular species with long generation times. Since long generations leave more time for mutations to accrue each generation, we posit that a long generation time likely amplifies the fitness consequences of any damage agent or DNA repair defect that creates extra mutations in the spermatogonia or oocytes. This leads to the counterintuitive prediction that the species with the highest germline mutation rates per generation are also the species with most effective mechanisms for avoiding and repairing mutations in their reproductive cells. Consistent with this, we show that mutation rates in the reproductive cells are inversely correlated with generation time; in contrast, the number of germline mutations that occur during prepuberty development trends weakly upward as generation time increases. Our results parallel recent findings that the longest-lived species have the lowest mutation rates in adult somatic tissues, potentially due to selection to keep the lifetime mutation load below a harmful threshold.
    Keywords:  generation time; germline; longevity; mutation rate; nearly neutral theory
    DOI:  https://doi.org/10.1073/pnas.2423311122
  4. Commun Biol. 2025 May 21. 8(1): 769
    UBE2V1 governs aging induced protein aggregation and developmental defects in oocytes and embryos.
    Ling Li, Ying Liu, Xi He, Junqing Chen, Xiaowei Guan, Longsen Han.
      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
  5. Bio Protoc. 2025 Mar 20. 15(6): e5242
    Visualization of mRNA Translation Within Germ Granule Biphasic Organization in Drosophila Early Embryo.
    Ali Haidar, Martine Simonelig, Anne Ramat.
      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
  6. Curr Opin Genet Dev. 2025 May 22. pii: S0959-437X(25)00057-7. [Epub ahead of print]93 102365
    Non-homologous sequence interactions during meiosis: meiotic challenges and evolutionary opportunities.
    Beth L Dumont, Mary Ann Handel.
      A hallmark of meiosis is pairing of homologous chromosomes, an event that ensures proper segregation into the gametes. Homology pairing is crucial to the formation of normal gametes, the maintenance of genomic integrity, and avoidance of aneuploidy. However, chromosomes are not completely homologous. Here we discuss two notable exceptions to homology: the mammalian sex chromosomes and centromeres. In themselves, these exceptions illustrate meiotic adaptations that both ensure correct chromosome segregation and present evolutionary opportunities. More broadly, such examples of non-homology provide a window for viewing normal mechanisms of meiotic pairing and chromosome modifications. Current analyses of mammalian meiotic chromosome dynamics suggest that the basis for the initial recognition of homology early in meiosis may be based in epigenetic chromatin modifications. Chromatin units may both form pairing sites and provide the modifications that allow non-homologous sequences to be tolerated. Despite recent research progress, we have yet to understand why some non-homologies are tolerated, while others lead to aneuploidy. Understanding how genomes evolve strategies to subvert the usual rules of meiosis will benefit from studies focused on the identification and characterization of meiosis in species with recently acquired non-homology. Looking forward, we are now armed with technologies and tools suited to precisely measure the extent of nonhomology across mammalian chromosomes and to probe the molecular and biophysical steps required for the initiation of homologous chromosome recognition and pairing. These goals are important for elucidating an essential mechanism of meiosis and ultimately for advancing the clinical diagnosis of gametic and embryo aneuploidy.
    DOI:  https://doi.org/10.1016/j.gde.2025.102365
  7. Genome Med. 2025 May 19. 17(1): 57
    RNA polymerase I is essential for driving the formation of 3D genome in early embryonic development in mouse, but not in human.
    Changliang Hou, Geng G Tian, Shuanggang Hu, Beili Chen, Xiaoyong Li, Bo Xu, Yuedi Cao, Wei Le, Rong Hu, Hao Chen, Yan Zhang, Qian Fang, Man Zhang, Zhaoxia Wang, Zhiguo Zhang, Jinfu Zhang, Zhaolian Wei, Guangxin Yao, Yefan Wang, Ping Yin, Ya Guo, Guoqing Tong, Xiaoming Teng, Yun Sun, Yunxia Cao, Ji Wu.
       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
  8. Nat Commun. 2025 May 23. 16(1): 4792
    RNA-binding proteins DND1 and NANOS3 cooperatively suppress the entry of germ cell lineage.
    Ziqi Wang, Honglin Yu, Zhaoyu Gu, Xiaohui Shi, Jiayue Ma, Qizhe Shao, Yao Yao, Shuo Yao, Yan Xu, Yashi Gu, Jiayue Dai, Qi Liu, Jingyan Shi, Rujie Qi, Yue Jin, Yuqian Liu, Xinchen Shen, Wenwen Huang, Heng-Jia Liu, Min Jin, Wanlu Liu, Matthew Brook, Di Chen.
      Specification of primordial germ cells (PGCs) establishes germline development during early embryogenesis, yet the underlying mechanisms in humans remain largely unknown. Here, we reveal the functional roles of germline-specific RNA-binding protein (RBP) DND1 in human PGC (hPGC) specification. We discovered that DND1 forms a complex with another RBP, NANOS3, to restrict hPGC specification. Furthermore, by analyzing the mRNAs bound by DND1 and NANOS3, we found that DND1 facilitates the binding of NANOS3 to hPGC-like cells-related mRNAs. We identified SOX4 mRNAs as the key downstream factor for the DND1 and NANOS3 complex. Mechanistically, DND1 and NANOS3 function in processing bodies (P-bodies) to repress the translation of SOX4 mRNAs, with NANOS3 mediating the interaction between DND1 and the translational repressor 4E-T. Altogether, these findings identify the RBP complex formed by DND1 and NANOS3 functioning as a "braking system" to restrict the entry of germ cell fate in humans.
    DOI:  https://doi.org/10.1038/s41467-025-57490-6
  9. EMBO Rep. 2025 May 23.
    Dynamic SAS-6 phosphorylation aids centrosome duplication and elimination in C. elegans oogenesis.
    Feifei Qi, Shanshan Yin, Xiangrui Yang, Ning Ju, Bohan Liu, Xing Zhang, Zixuan Zhu, Li Ji, Fuxin Zhang, Li Zhao, Ruoxi Wang, Min Liu, Liangran Zhang, Huijie Zhao, Jun Zhou, Jinmin Gao.
      In most metazoans, centrosome elimination during oogenesis ensures accurate centriole inheritance in the zygote, yet the molecular mechanisms remain poorly understood. Here, we reveal a critical role for controlled SAS-6 phosphorylation in centrosome dynamics during oogenesis. Centrioles disassemble during late meiotic prophase, while the cartwheel protein SAS-6 exhibits dynamic behavior in early meiotic prophase. Purified SAS-6 undergoes phase separation in vitro, and overexpressed SAS-6 forms droplets in cells. Mass spectrometry and kinase assays reveal that SAS-6 is phosphorylated at its C-terminus in cells and in vivo, with CDK-1 identified as a direct kinase. This phosphorylation inhibits SAS-6 phase separation and weakens interactions between centriolar proteins. SAS-6 degradation confirms its role in centrosome stability, and CDK-1 activity is required for timely centriole disassembly. Phospho-mimetic and phospho-deficient mutants demonstrate that dynamic SAS-6 phosphorylation is essential for centrosome assembly and elimination. We propose that the disordered C-terminus of SAS-6 facilitates cartwheel stacking via multivalent weak interactions, promoting centriole stability. Phosphorylation disrupts these interactions, impairing centrosome duplication and promoting elimination during oogenesis.
    Keywords:  CDK-1; Centrosome Elimination; Oogenesis; Phase Separation; SAS-6
    DOI:  https://doi.org/10.1038/s44319-025-00485-7
  10. FEBS Lett. 2025 May 19.
    Molecular insights into RNA recognition by the ZAR1 C-terminal domain.
    Qingling Liu, Haoyu Ma, Xian He, Chao Xu, Jiahai Zhang.
      Zygote arrested-1 (ZAR1)-dependent translational repression plays an important role during early oogenesis. Here, we solved the crystal structure of the C-terminal domain of ZAR1, which contains three zinc-binding motifs, and confirmed its ability to bind to RNAs derived from translation control sequence elements within the 3'-UTRs of Wee1 and Mos mRNAs. By using the AlphaFold server, we obtained a predicted model for the structure of the ZAR1 C-terminal domain bound with a 13-nt RNA. Mutagenesis and biochemistry experiments further validated the ZAR1-RNA interaction. Therefore, our study provides insights into RNA recognition by the ZAR1 zinc-binding domain and the role of ZAR1 in repressing gene expression. Impact statement Zygote arrested-1 (ZAR1)-dependent translational repression finely orchestrates gene expression during early oogenesis. Here, we solved the high-resolution structure of the C-terminal zinc-binding domain of ZAR1 and confirmed its binding to RNA. The modeled ZAR1-RNA complex by Alphafold further provides insight into RNA recognition by ZAR1.
    Keywords:  NMR titration; RNA‐binding protein; chemical shift perturbation; crystal structure; zinc‐binding domain
    DOI:  https://doi.org/10.1002/1873-3468.70080
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