bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–04–20
eleven papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. The subcortical maternal complex safeguards mouse oocyte-to-embryo transition by preventing nuclear entry of SPIN1.
  2. Cell cycle and age-related modulations of mouse chromosome stiffness.
  3. Disrupted MOS signaling alters meiotic cell cycle regulation and the egg transcriptome.
  4. The differential roles of rad9 alternatively spliced forms in double- strand DNA break repair during Drosophila meiosis.
  5. Age-related changes in the cytoplasmic ultrastructure of feline oocytes.
  6. Granulosa cell transcription is similarly impacted by superovulation and aging and predicts early embryonic trajectories.
  7. Mechanisms of chemotherapy-induced oocyte death through activation of TAp63α.
  8. Zygotic activation of transposable elements during zebrafish early embryogenesis.
  9. Label-free evaluation of mouse embryo quality using time-lapse bright field and optical coherence microscopy.
  10. Meiotic spindle pushed outward by inward organelle packing.
  11. From conservation to adaptation: understanding the synaptonemal complex's evolutionary dynamics.
  1. Nat Struct Mol Biol. 2025 Apr 17.
    The subcortical maternal complex safeguards mouse oocyte-to-embryo transition by preventing nuclear entry of SPIN1.
    Chengpeng Xu, Dandan Qin, Xukun Lu, Qianqian Qi, Yu Wu, Qizhi Wang, Zhuo Han, Xiaoqing Nie, Yongmei Jiang, Dong Deng, Wei Xie, Zheng Gao, Lei Li.
      How cytoplasmic regulators control nuclear events in mammalian oocytes and early embryos remains largely enigmatic. We previously identified a subcortical maternal complex (SCMC) that specifically resides in the cytoplasm of mammalian oocytes and early embryos but is also involved in nuclear events. Nevertheless, how the cytoplasmic SCMC exerts its role in nuclear processes remains unknown. In this study, we unveil SPIN1, a histone methylation reader, as a novel member of the SCMC. The SCMC component FILIA tightly regulates the expression and cytoplasmic localization of SPIN1 through direct interaction. When the expression of FILIA is decreased because of genetic mutations of SCMC genes, SPIN1 expression is dramatically reduced but the residual SPIN1 translocates into the nucleus. The abnormal nuclear presence of SPIN1 impairs H3K4me3 reprogramming, zygotic genome activation and physiological embryonic development. Inhibiting the interaction between SPIN1 and H3K4me3 partially rescues the abnormal phenotype in FILIA-null embryos. Mechanistically, SPIN1 partially perturbs the demethylation process by competing with KDM5B for binding to H3K4me3. Collectively, our work highlights the complexity of the mammalian SCMC and oocyte-to-embryo transition, revealing an intricate regulatory mechanism that facilitates the smooth progression of this process.
    DOI:  https://doi.org/10.1038/s41594-025-01538-0
  2. Elife. 2025 Apr 14. pii: RP97403. [Epub ahead of print]13
    Cell cycle and age-related modulations of mouse chromosome stiffness.
    Ning Liu, Wenan Qiang, Philip W Jordan, John F Marko, Huanyu Qiao.
      Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a tenfold increase in stiffness (Young's modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower than that of MI chromosomes. We examined the role of meiosis-specific cohesin complexes in regulating chromosome stiffness. Surprisingly, the stiffness of chromosomes from three meiosis-specific cohesin mutants did not significantly differ from that of wild-type chromosomes, indicating that these cohesins may not be primary determinants of chromosome stiffness. Additionally, our findings revealed an age-related increase of chromosome stiffness for MI oocytes. Since aging is associated with elevated levels of DNA damage, we investigated the impact of etoposide-induced DNA damage on chromosome stiffness and found that it led to a reduction in stiffness in MI oocytes. Overall, our study underscores the dynamic and cyclical nature of chromosome stiffness, modulated by both the cell cycle and age-related factors.
    Keywords:  age; chromosome stiffness; cohesin protein; meiosis; mouse; oocyte; physics of living systems; spermatocyte
    DOI:  https://doi.org/10.7554/eLife.97403
  3. bioRxiv. 2025 Apr 03. pii: 2025.04.02.646881. [Epub ahead of print]
    Disrupted MOS signaling alters meiotic cell cycle regulation and the egg transcriptome.
    Gisela Cairo, Olha Kholod, Olivia Palmer, Brittany A Goods, Soni Lacefield.
      Mammalian female meiosis is tightly regulated to produce a developmentally competent egg. Oocytes enter meiosis in the fetal ovary and then arrest at prophase I until sexual maturation. Upon hormonal stimulation, a subset of oocytes resumes meiosis at which time, new transcription is halted. Oocytes then complete meiosis I, enter metaphase II, and arrest until fertilization, a process essential for egg competency and fertility. The MOS kinase is a key regulator of the metaphase II arrest, activating the MAPK signaling cascade. Loss of MOS in female mice disrupts the maintenance of the metaphase II arrest, leading some eggs to extrude two polar bodies and some to divide beyond anaphase II. To investigate the consequences of the Mos deletion, we performed live imaging and found that mos -/- eggs exhibit transient chromosome separation events in meiosis I, suggesting a role for MOS in coordinating the timing of meiotic divisions. Further analysis showed that new transcription is required for mos -/- eggs to undergo additional divisions but not for second polar body extrusion. Surprisingly, single-egg sequencing revealed extensive differences in gene expression between wildtype and mos -/- eggs, including those with only one polar body. Many of the differentially expressed genes were involved in cell cycle regulation, including Aurka , Bub3 , and Cdk7 . Other upregulated pathways included metabolism of RNA, transcription, and neddylation. Furthermore, the gene expression profile of mos -/- eggs was markedly different from that of wildtype eggs chemically activated to undergo embryo-like divisions. Our findings demonstrate that MOS plays a crucial role in meiotic cell cycle regulation and helps ensure that the egg maintains the proper transcriptome necessary for developmental competence.
    DOI:  https://doi.org/10.1101/2025.04.02.646881
  4. DNA Repair (Amst). 2025 Apr 08. pii: S1568-7864(25)00029-1. [Epub ahead of print]149 103833
    The differential roles of rad9 alternatively spliced forms in double- strand DNA break repair during Drosophila meiosis.
    Bareket Goldstein, Suad Sheikh-Suliman, Anna Bakhrat, Uri Abdu.
      The 9-1-1 complex, comprising the Rad9, Hus1 and Rad1 proteins, is believed to operate as a component of a DNA damage checkpoint pathway. Our initial analysis of the Drosophila hus1 gene showed that Hus1 plays a dual role in meiosis, regulating both meiotic DNA damage checkpoint and homologous recombination repair. In this study, we further analyzed the meiotic roles of another protein in the complex, Rad9, which has two alternatively spliced forms, Rad9A and Rad9B. Using CRISPR/Cas9, we generated flies mutant for both rad9 isoforms. We found that, similarly to hus1, mutations in rad9 lead to female sterility. Also, double-strand DNA breaks (DSBs) that form during meiosis are not processed efficiently, and the DNA within the oocyte nucleus fails to form its characteristic shape in rad9 mutants. On the other hand, the hus1 mutation completely disrupts checkpoint activation in DSB repair enzyme mutants, whereas the rad9 mutation only partially impairs checkpoint activation in this context. Moreover, spatial rescue experiments revealed that Rad9B is efficient in repairing meiotic DSBs, while Rad9A is not. Furthermore, we found that female fertility in rad9 mutants depends on early efficient meiotic DSB repair but not on karyosome formation. In summary, our results demonstrate a differential role of Rad9 alternatively spliced forms during Drosophila meiosis in oogenesis, and while former studies showed that Hus1 is sufficient for the effective activation of the meiotic recombination checkpoint, our results revealed that this is not true for Rad9.
    Keywords:  9–1–1 complex; DSB repair; Dorsal-ventral eggshell patterning; Drosophila; Karyosome; Meiotic recombination checkpoint; Rad9
    DOI:  https://doi.org/10.1016/j.dnarep.2025.103833
  5. Sci Rep. 2025 Apr 12. 15(1): 12668
    Age-related changes in the cytoplasmic ultrastructure of feline oocytes.
    Brągiel Natalia, Perrin John, Młodawska Wiesława, Niżański Wojciech, Podhorska-Okołów Marzenna, Haczkiewicz-Leśniak Katarzyna, Kulus Michał, Ochota Małgorzata.
      This study elucidates the impact of aging on the cellular architecture of feline oocytes, with a particular emphasis on organelles essential for fertilization and embryo development. Using transmission electron microscopy (TEM), the research compares oocytes from prepubescent, cycling adult, and aged cats, revealing notable differences in the arrangement of key structures, particularly mitochondria, lipid droplets, and vacuoles. Oocytes from adult donors are at their metabolic peak, demonstrating a higher concentration of mitochondria near lipid droplets, supporting efficient energy metabolism. In contrast, younger and older oocytes exhibit larger lipid droplets and reduced mitochondrial density, indicative of diminished metabolic activity. These findings not only underscore the necessity of selecting an optimal donor age for in vitro fertilization but also suggest potential biomarkers for oocyte quality assessment. This novel insight offers promising strategies to enhance reproductive success, improve assisted reproduction outcomes, and support feline conservation efforts.
    Keywords:  Aging; Cats; Electron microscopy; Fertility; Oocytes; Reproductive biology
    DOI:  https://doi.org/10.1038/s41598-025-96983-8
  6. Nat Commun. 2025 Apr 17. 16(1): 3658
    Granulosa cell transcription is similarly impacted by superovulation and aging and predicts early embryonic trajectories.
    Klaudija Daugelaite, Perrine Lacour, Ivana Winkler, Marie-Luise Koch, Anja Schneider, Nina Schneider, Francesca Coraggio, Alexander Tolkachov, Xuan Phuoc Nguyen, Adriana Vilkaite, Julia Rehnitz, Duncan T Odom, Angela Goncalves.
      In vitro fertilization efficiency is limited in part because a fraction of retrieved oocytes fails to fertilize. Accurately evaluating their quality could significantly improve in vitro fertilization efficiency, which would require better understanding how their maturation may be disrupted. Here, we quantitatively investigate the interplay between superovulation and aging in mouse oocytes and their paired granulosa cells using a newly adapted experimental methodology. We test the hypothesis that superovulation disrupts oocyte maturation, revealing the key intercellular communication pathways dysregulated at the transcriptional level by forced hormonal stimulation. We further demonstrate that granulosa cell transcriptional markers can prospectively predict an associated oocyte's early developmental potential. By using naturally ovulated old mice as a non-stimulated reference, we show that aging and superovulation dysregulate similar genes and interact with each other. By comparing mice and human transcriptional responses of granulosa cells, we find that age-related dysregulation of hormonal responses and cell cycle pathways are shared, though substantial divergence exists in other pathways.
    DOI:  https://doi.org/10.1038/s41467-025-58451-9
  7. Reproduction. 2025 Apr 01. pii: REP-24-0225. [Epub ahead of print]
    Mechanisms of chemotherapy-induced oocyte death through activation of TAp63α.
    Niklas Gutfreund, Marcel Tuppi, Birgit Schäfer, Francesca Gioia Klinger, Anja Kirchhof, Antonia Hofmann, Ivan Dikic, Volker Dotsch.
      Premature ovarian insufficiency (POI) is a severe side effect of classical chemotherapy and radiotherapy in treatment of female cancer patients of reproductive age. The molecular mechanisms underlying POI are diverse, ranging from altered hormone levels to decimated resting oocyte reserve by apoptosis or elevated recruitment. The p53-homolog TAp63α emerged as the key protein regulating apoptosis following DNA damage in primary oocytes. In this study we monitored the ovotoxicity of widely used chemotherapeutic agents utilizing a GFP-c-Kit transgenic mouse model, the involvement of active TAp63α and the mechanism of action leading to its activation. Our studies show that alkylating agents as well as topoisomerase II poisons are potent activators of TAp63α by directly inducing DNA damage. Oxidative stress as well as DNA-intercalation were not sufficient to trigger TAp63α activation despite showing a strong general ovotoxicity. These results are in agreement with several previous investigations that have demonstrated that DNA double strand breaks are the most effective way to initiate apoptosis in primordial follicles. The widely used catalytic topoisomerase II inhibitor ICRF-187 were able to prevent doxorubicin-mediated activation of TAp63α by the topoisomerase II poisons doxorubicin.
    DOI:  https://doi.org/10.1530/REP-24-0225
  8. Nat Commun. 2025 Apr 18. 16(1): 3692
    Zygotic activation of transposable elements during zebrafish early embryogenesis.
    Bo Li, Ting Li, Dingjie Wang, Ying Yang, Puwen Tan, Yunhao Wang, Yun-Gui Yang, Shunji Jia, Kin Fai Au.
      Although previous studies have shown that transposable elements (TEs) are conservatively activated to play key roles during early embryonic development, the details of zygotic TE activation (ZTA) remain poorly understood. Here, we employ long-read sequencing to precisely identify that only a small subset of TE loci are activated among numerous copies, allowing us to map their hierarchical transcriptional cascades at the single-locus and single-transcript level. Despite the heterogeneity of ZTA across family, subfamily, locus, and transcript levels, our findings reveal that ZTA follows a markedly different pattern from conventional zygotic gene activation (ZGA): ZTA occurs significantly later than ZGA and shows a pronounced bias for nuclear localization of TE transcripts. This study advances our understanding of TE activation by providing a high-resolution view of TE copies and creating a comprehensive catalog of thousands of previously unannotated transcripts and genes that are activated during early zebrafish embryogenesis. Among these genes, we highlight two that are essential for zebrafish development.
    DOI:  https://doi.org/10.1038/s41467-025-58863-7
  9. Commun Biol. 2025 Apr 15. 8(1): 612
    Label-free evaluation of mouse embryo quality using time-lapse bright field and optical coherence microscopy.
    Fei Wang, Senyue Hao, Kibeom Park, Ali Ahmady, Chao Zhou.
      The selection of high-quality embryos is essential to enhance the implantation rate for in vitro fertilization (IVF). Optical coherence microscopy (OCM) can noninvasively provide three-dimensional (3D) high-resolution imaging of developing embryos. The revealed microstructures can be used for accurate embryo evaluation. Here, we acquire time-lapse 3D OCM images with co-registered bright-field imaging on mouse embryo development from the one-cell stage to the fully hatched blastocyst inside an incubator. Our results demonstrate the capability of OCM to detect structural features of the developing embryos. The second and third embryonic cell cycles are indicated to be associated with blastocyst formation and the hatching capability. OCM-based time-lapse technology holds the potential to enrich early embryo development insights and streamline embryo selection within IVF clinics.
    DOI:  https://doi.org/10.1038/s42003-025-08044-5
  10. Trends Cell Biol. 2025 Apr 10. pii: S0962-8924(25)00086-8. [Epub ahead of print]
    Meiotic spindle pushed outward by inward organelle packing.
    Xin Xiang.
      In Caenorhabditis elegans oocytes, meiotic spindle movement toward the cortex before anaphase depends on kinesin-1. A recent study by Aquino et al. uncovers a novel mechanism whereby the inward organelle packing driven by kinesin-1 excludes the spindle from the center, thereby causing it to be positioned near the cortex.
    Keywords:  C. elegans oocyte; kinesin-1; microtubule polarity; organelle movement; spindle positioning; volume exclusion
    DOI:  https://doi.org/10.1016/j.tcb.2025.03.006
  11. Curr Opin Genet Dev. 2025 Apr 16. pii: S0959-437X(25)00041-3. [Epub ahead of print]93 102349
    From conservation to adaptation: understanding the synaptonemal complex's evolutionary dynamics.
    Stefanie Williams, Robin Scott Hawley.
      The synaptonemal complex (SC) is structurally conserved across eukaryotes and is essential for a proper progression of meiosis. Despite this conservation, SC protein sequences diverge drastically. In this review, we explore findings on SC protein evolution, highlighting key differences and commonalities among lineages like the Caenorhabditis and the Drosophila genera. We further explore known cases where the SC and its proteins adopt novel functional roles and discuss why knowledge of these cases could be important for the study of canonical SC biology. The existing studies demonstrate that work on the evolutionary biology of SC proteins and functional studies in more diverse meiotic research organisms should play a major role in aiding our understanding of SC structure and functions.
    DOI:  https://doi.org/10.1016/j.gde.2025.102349
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