bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2025–02–02
six papers selected by
Gabriele Zaffagnini, Universität zu Köln



  1. Cell. 2025 Jan 17. pii: S0092-8674(24)01470-3. [Epub ahead of print]
      Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our comprehensive solution of ultrasensitive proteomic technology to measure the proteomic profiles of oocytes and early embryos and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species. Integrative analysis with translatomic data revealed extensive divergence between translation activation and protein accumulation. Multi-omic analysis indicated that ZGA transcripts often contribute to protein accumulation in blastocysts. Using mouse embryos, we identified several transcriptional regulators critical for early development, thereby linking ZGA to the first lineage specification. Furthermore, single-embryo proteomics of poor-quality embryos from over 100 patient couples provided insights into preimplantation development failure. Our study may contribute to reshaping the framework of mammalian preimplantation development and opening avenues for addressing human infertility.
    Keywords:  ZGA; human preimplantation development; multi-omic analysis; poor-quality embryo; ultrasensitive proteomics
    DOI:  https://doi.org/10.1016/j.cell.2024.12.028
  2. Dev Cell. 2025 Jan 18. pii: S1534-5807(25)00002-4. [Epub ahead of print]
      Apoptosis is a key feature of preimplantation development, but whether it occurs in a cell-autonomous or coordinated manner was unknown. Here, we report that plasma membrane abscission, the final step of cell division, is profoundly delayed in early mouse embryos such that a cytokinetic bridge is maintained for the vast majority of the following interphase. Early embryos thus consist of many pairs of sister cells connected by stable cytokinetic bridges that allow them to share diffusible molecules. We show that apoptotic regulators are shared through cytokinetic bridges and that these bridges ensure that if one cell enters apoptosis, its sister cell does as well. Long-lived cytokinetic bridges are thus a previously unappreciated form of cell-cell communication within the mouse embryo that coordinate the clearance of pairs of cells with similar developmental histories.
    Keywords:  abscission; apoptosis; cytokinesis; cytokinetic bridge; embryo; mitosis
    DOI:  https://doi.org/10.1016/j.devcel.2025.01.002
  3. STAR Protoc. 2025 Jan 30. pii: S2666-1667(25)00010-3. [Epub ahead of print]6(1): 103604
      Mouse oocytes devoid of branched actin display prolonged cortical contractions during the first meiotic division. Here, we present a protocol to collect fully grown oocytes in prophase I arrest and record their contractions during the first meiotic division through time-lapse imaging in transillumination, without additional labeling. We then explain how to set up the pipeline to segment the oocyte outline with an ImageJ plugin Oocytor and to measure cortical fluctuations with the help of an ImageJ plugin Radioak. For complete details on the use and execution of this protocol, please refer to Nikalayevich et al.1.
    Keywords:  cell culture; developmental biology; microscopy; single cell
    DOI:  https://doi.org/10.1016/j.xpro.2025.103604
  4. Commun Biol. 2025 Jan 29. 8(1): 141
      In mammalian oocytes, large-scale chromatin organization regulates transcription, nuclear architecture, and maintenance of chromosome stability in preparation for meiosis onset. Pre-ovulatory oocytes with distinct chromatin configurations exhibit profound differences in metabolic and transcriptional profiles that ultimately determine meiotic competence and developmental potential. Here, we developed a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live mouse oocytes. Our Fluorescence prediction and Classification on Bright-field (Fluo-Cast-Bright) pipeline achieved 91.3% accuracy in the classification of chromatin state in fixed oocytes and 85.7% accuracy in live oocytes. Importantly, transcriptome analysis following non-invasive selection revealed that meiotically competent oocytes exhibit a higher expression of transcripts associated with RNA and protein nuclear export, maternal mRNA deadenylation, histone modifications, chromatin remodeling and signaling pathways regulating microtubule dynamics during the metaphase-I to metaphase-II transition. Fluo-Cast-Bright provides fast and non-invasive selection of meiotically competent oocytes for downstream research and clinical applications.
    DOI:  https://doi.org/10.1038/s42003-025-07568-0
  5. PLoS Genet. 2025 Jan 29. 21(1): e1011400
      Mitosis and meiosis have two mechanisms for regulating the accuracy of chromosome segregation: error correction and the spindle assembly checkpoint (SAC). We have investigated the function of several checkpoint proteins in meiosis I of Drosophila oocytes. Increased localization of several SAC proteins was found upon depolymerization of microtubules by colchicine. However, unattached kinetochores or errors in biorientation of homologous chromosomes do not induce increased SAC protein localization. Furthermore, the metaphase I arrest does not depend on SAC genes, suggesting the APC is inhibited even if the SAC is not functional. Two SAC proteins, ROD of the ROD-ZW10-Zwilch (RZZ) complex and MPS1, are also required for the biorientation of homologous chromosomes during meiosis I, suggesting an error correction function. Both proteins aid in preventing or correcting erroneous attachments and depend on SPC105R for localization to the kinetochore. We have defined a region of SPC105R, amino acids 123-473, that is required for ROD localization and biorientation of homologous chromosomes at meiosis I. Surprisingly, ROD removal from kinetochores and movement towards spindle poles, termed "streaming," is independent of the dynein adaptor Spindly and is not linked to the stabilization of end-on attachments. Instead, meiotic RZZ streaming appears to depend on cell cycle stage and may be regulated independently of kinetochore attachment or biorientation status. We also show that Spindly is required for biorientation at meiosis I, and surprisingly, the direction of RZZ streaming.
    DOI:  https://doi.org/10.1371/journal.pgen.1011400
  6. Proc Natl Acad Sci U S A. 2025 Feb 04. 122(5): e2422694122
      Understanding how epithelial cells in the female reproductive tract (FRT) differentiate is crucial for reproductive health, yet the underlying mechanisms remain poorly defined. At birth, FRT epithelium is highly malleable, allowing differentiation into various epithelial types, but the regulatory pathways guiding these early cell fate decisions are unclear. Here, we use neonatal mouse endometrial organoids and assembloid coculture models to investigate how innate cellular plasticity and external mesenchymal signals influence epithelial differentiation. Our findings demonstrate that uterine epithelium undergoes marked age-dependent changes, transitioning from a highly plastic state capable of forming both monolayered and multilayered structures to a more restricted fate as development progresses. Interestingly, parallels emerge between the developmental plasticity of neonatal uterine epithelium and pathological conditions such as endometrial cancer, where similar regulatory mechanisms may reactivate, driving abnormal epithelial differentiation and tumorigenesis. These results not only deepen our understanding of early uterine development but also offer a valuable model for studying the progression of reproductive diseases and cancers.
    Keywords:  assembloids; development; epithelium; organoid; uterus
    DOI:  https://doi.org/10.1073/pnas.2422694122