bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–05–17
eight papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. The Balbiani body at a glance.
  2. Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events.
  3. CCDC174 deficiency impaired human fertility by affecting the alternative splicing of maternal mRNAs.
  4. Gene regulatory networks orchestrating oocyte fate bifurcation in primordial follicles revealed by single-cell transcriptomics.
  5. The mid-pachytene transition between early and late double-strand breaks in C. elegans meiosis is conserved throughout early adulthood and coincides with a peak in recombination intermediates.
  6. Protocol for ex vivo culture of neonate mouse ovaries to study early follicle activation.
  7. Dual recombinases-mediated genetic tracing reveals no postnatal neo-oogenesis in mice.
  8. Generation of human primordial germ cell-like cells from cumulus and blood cell-derived isogenic hiPSCs†.
  1. J Cell Sci. 2026 May 01. pii: jcs264644. [Epub ahead of print]139(9):
    The Balbiani body at a glance.
    Swastik Kar, Yaniv M Elkouby.
      The Balbiani body (Bb) is a conserved membraneless compartment that assembles in early oocytes across animal species and is required for oocyte growth, polarity and developmental competence. It is composed of RNA-protein complexes and enriched organelles, and is a molecular condensate that integrates and spatially organizes transcripts, mitochondria and regulatory factors. Although its core architecture is conserved, its roles vary across species, supporting RNA storage and localization, mitochondrial selection and quality control, translational regulation and cytoplasmic patterning. Bb assembly is initiated by phase separation of seed proteins and reinforced by microtubule-dependent transport and scaffolding. The condensate subsequently matures into a stable solid-like structure and later undergoes regulated actin-dependent disassembly at the oocyte cortex. This ordered progression enables controlled concentration, stabilization and targeted delivery of developmental determinants required for oogenesis and early embryonic development. Elucidating these mechanisms provides a tractable framework for understanding how biomolecular condensation and cytoskeletal organization generate functional compartments in cells, with broad implications for cell, developmental and reproductive biology. An accompanying poster summarizes its composition, assembly and dynamics, and highlights species-specific functions and remaining questions.
    Keywords:  Actin; Balbiani body; Bucky ball; Centrosome; Membraneless compartments; Microtubules; Molecular condensation; Oocyte development; Reproduction; XVelo
    DOI:  https://doi.org/10.1242/jcs.264644
  2. Nat Commun. 2026 May 13.
    Greatwall depletion from Xenopus oocytes reveals a key role of the cyclin B/CDK1-PP2A-B55 balance in the coordination of meiotic events.
    Sylvain Roque, Célia Ben Choug, Cedric Hassen Khodja, Suzanne Vigneron, Véronique Legros, Guillaume Chevreux, Benjamin Lacroix, Anna Castro, Thierry Lorca.
      Meiotic progression relies on maintaining a precise balance between cyclin B/CDK1 activity and the phosphatase PP2A-B55. The latter is negatively regulated by the Greatwall kinase (Gwl). In maturing Xenopus oocytes, we show that the loss of Gwl and the subsequent hyperactivation of PP2A-B55 prevents phosphorylation of key proteins involved in spindle formation, chromosome condensation and spindle migration as well as the phosphorylation of Wee1/Myt1 and the APC/C complex. As a consequence, in these oocytes bipolar spindles cannot be formed and migrate to the cortex and chromosomes are partially decondensed preventing meiotic I progression. The APC/C remains inactive impairing cyclin B3 degradation and ultimately preventing Erp1 accumulation. Finally, the c-Mos-MAPK-Rsk1/2 pathway fails to activate due to the absence of c-Mos as a consequence of its improper degradation. Overall, our findings reveal a crucial role of Gwl in the coordination and progression of meiotic divisions.
    DOI:  https://doi.org/10.1038/s41467-026-73011-5
  3. EMBO Mol Med. 2026 May 12.
    CCDC174 deficiency impaired human fertility by affecting the alternative splicing of maternal mRNAs.
    Weijie Wang, Zhiqi Pan, Huixia Jing, Rong Shi, Ling Wu, Jinjie Wang, Biaobang Chen, Jian Mu, Zhihua Zhang, Tianyu Wu, Qiaoli Li, Juanzi Shi, Yanping Kuang, Lin He, Lei Wang, Qing Sang.
      Precise regulation of alternative splicing (AS) of maternal mRNAs is crucial for maintaining mRNA homeostasis and for acquiring oocyte competence. However, the regulatory factors and mechanisms of AS regulating oocyte competence and human fertility remain largely unknown. Here, we identified biallelic variants in CCDC174 that cause human oocyte competence defects and female infertility. Oocyte-specific knockout of Ccdc174 resulted in oocyte maturation arrest and female infertility in mice, and transcriptomic and proteomic analyses indicated that deletion of Ccdc174 disrupted mRNA and protein homeostasis as well as AS in oocytes. Importantly, we found that CCDC174 interacted with the splicing machinery-related PRP19/CDC5L complex, and loss of CCDC174 led to aberrant activation of the expression of these complex members in oocytes. In addition, in vitro studies indicated that patient-derived variants impaired the expression of CCDC174 and its binding to RNAs or CDC5L. Taken together, our study not only show that CCDC174 is a novel AS regulator that maintains mRNA homeostasis and oocyte competence, but also decipher the critical role of CCDC174 deficiency in the pathogenesis of female infertility.
    DOI:  https://doi.org/10.1038/s44321-026-00448-y
  4. Commun Biol. 2026 May 09.
    Gene regulatory networks orchestrating oocyte fate bifurcation in primordial follicles revealed by single-cell transcriptomics.
    Hanwen Zhang, Xingsi He, Qiuzhen Chen, Min Su, Huanyu Yan, Xiao Zeng, Shicai Fan, Xi Wang.
      The first wave of primordial follicle activation occurs around postnatal day 2.5 (P2.5), with the remaining follicles entering a dormant state to ensure a continuous supply of fertilizable oocytes. However, the molecular characterization and underlying mechanisms of this critical fate commitment remain poorly understood. Here, we employ SMART-seq2 to profile transcriptional dynamics in individual perinatal female C57BL/6 mouse germ cells across three developmental stages: cyst stage at embryonic day 17.5 (E17.5), primordial-follicle stage at P2.5, and primary-follicle stage at P6.5. Unsupervised clustering and trajectory inference reveal divergent transcriptional programs within P2.5 primordial oocytes, indicative of a bifurcating process in which pre-determined oocytes commit towards either dormant or activated states. Activated oocytes exhibit upregulation of genes linked to PI3K-Akt/mTORC1 signaling, extracellular matrix (ECM) disassembly, and oocyte maturation, whereas marker genes of dormant oocytes are enriched in oxidative stress response and DNA repair pathways. Transcriptional regulatory network reconstruction based on SCENIC inference identifies key transcription factors (e.g., BHLHE41, TCF3/12) orchestrating the fate bifurcation. Notably, dormant oocytes form a stable transcriptional state distinct from the continuous activation and development trajectory. Our findings provide a comprehensive landscape of gene expression and regulatory networks that orchestrate fate determination in P2.5 primordial-follicle oocytes.
    DOI:  https://doi.org/10.1038/s42003-026-10235-7
  5. G3 (Bethesda). 2026 May 14. pii: jkag130. [Epub ahead of print]
    The mid-pachytene transition between early and late double-strand breaks in C. elegans meiosis is conserved throughout early adulthood and coincides with a peak in recombination intermediates.
    Hui Tian, Korie Campbell, Sarit Smolikove.
      In meiosis, SPO-11-induced DNA double-strand breaks (DSBs) are repaired via two main homologous recombination pathways: the double Holliday Junction pathway, which yields crossovers (COs), and the synthesis-dependent strand annealing pathway, which generates non-crossover (NCOs). The standard model assumes that the choice between these two outcomes occurs simultaneously and late in the pathway, following strand invasion. We previously demonstrated that in Caenorhabditis elegans this decision is made early: DSBs formed early in meiotic prophase are destined for NCOs, while late DSBs are committed to COs. In this study we aimed to identify if and how the time window for early-to-late DSB transition is altered when the germline grows. It is established that the germline grows as a worm develops through early adulthood. We find that the expansion of the pachytene stage of meiotic prophase I is the main driver for germline growth. We further characterize the movement of meiotic nuclei and identify that while the average movement rate is consistent with previous studies, surprisingly, nuclear movement gradually slows during meiotic prophase I. Furthermore, the late DSB (CO-fated) region expands proportionally with the growing pachytene, consistently corresponding to the proximal half of the pachytene region. These findings indicate that the early-to-late DSB transition coincides with the peak of RAD-51 foci numbers, which remains stably positioned at the middle of pachytene during germline growth. Thus, our data not only provide a precise measurement of early adult germline development but also suggest that the time window for early-to-late DSB transition coincides with mid-pachytene signaling.
    Keywords:   C. elegans ; DSB; WormBase; crossover; meiosis
    DOI:  https://doi.org/10.1093/g3journal/jkag130
  6. STAR Protoc. 2026 May 08. pii: S2666-1667(26)00192-9. [Epub ahead of print]7(2): 104539
    Protocol for ex vivo culture of neonate mouse ovaries to study early follicle activation.
    Julie Feld Madsen, Stine Bundgaard Birkebæk, Karin Lykke-Hartmann.
      Establishing an ex vivo culture of neonatal ovaries enables controlled investigation of early follicle dynamics. Here, we present a protocol for isolating ovaries from neonatal female mice for maintaining intact ovarian architecture by ex vivo culture on a membrane allowing access to defined medium. We describe procedures for media preparation, ovary dissection, culture setup, and follicle development by stereomicroscopy and histological assessment. This protocol provides a platform for examining the regulation of the primordial-to-primary transition and growth. For complete details on the use and execution of this protocol, please refer to Amoushahi et al.1.
    Keywords:  Cell Biology; Cell culture; Developmental biology; Model Organisms; Molecular Biology
    DOI:  https://doi.org/10.1016/j.xpro.2026.104539
  7. iScience. 2026 May 15. 29(5): 115830
    Dual recombinases-mediated genetic tracing reveals no postnatal neo-oogenesis in mice.
    Heng Xie, Bin Zhou, Ping Zheng.
      The existence of postnatal neo-oogenesis in mammals has been debated since the initial reports of ovarian germline stem cells. To address this question, we employed a dual-recombinase-mediated genetic tracing system (Cre-loxP and Dre-rox). Pre-existing germ cells present after birth were labeled with ZsGreen via Stra8-Cre, whereas other ovarian cells were marked with tdTomato through tamoxifen-inducible Dre expression. Under physiological conditions, tdTomato+ cells labeled in young adult (8-week old), pubertal (3-week old), and newborn mice were traced for periods ranging from one to ten months. Regardless of the tracing duration, no tdTomato+ growing oocytes or metaphase II (MII) eggs were detected. Similarly, following busulfan-induced ovarian injury, no tdTomato+ growing oocytes or MII eggs were regenerated. Taken together, these findings provide compelling evidence against the occurrence of in vivo neo-oogenesis in mice, with implications for human reproductive biology.
    Keywords:  Cell biology; Molecular biology experimental approach; Molecular genetics
    DOI:  https://doi.org/10.1016/j.isci.2026.115830
  8. Biol Reprod. 2026 May 11. pii: ioag101. [Epub ahead of print]
    Generation of human primordial germ cell-like cells from cumulus and blood cell-derived isogenic hiPSCs†.
    Silvia Llonch, Laurie Pinel, Tom Mattimoe, Jacqueline Severino, Filippo Zambelli, Anna Mallol, Karen Freire Carvalho, Laura Batlle-Morera, Rita Vassena, Bernhard Payer.
      The recent development of in vitro germ cell differentiation from pluripotent stem cells opened the human reproduction field to mechanistic investigations. In combination with induced pluripotent stem cell (hiPSC) reprogramming, in vitro gametogenesis provides an avenue for patient-specific disease modeling approaches. However, further advancements are required, as current protocols are limited to early stages of germ cell development. To get one step closer to this goal, here we aimed to identify optimal conditions for generating high-quality hiPSC lines capable of in vitro germ cell differentiation. We isolated two clinically available somatic cell types, peripheral blood-derived mononuclear cells (PBMCs) and cumulus cells from the same female donor, and reprogrammed them into hiPSCs. We then assessed their differentiation into ectoderm, mesoderm, and endoderm, and evaluated their X-chromosome inactivation status, a critical indicator of stem cell quality. Finally, we compared the capacity of PBMC- and cumulus-derived hiPSCs to differentiate into human primordial germ cell-like cells (hPGCLCs). We found that despite variability between cell lines, hiPSCs from both cell types were capable of generating hPGCLCs and that variations in X-chromosome state did not appear to generally interfere with the process. Our findings provide insight into germ cell differentiation from different clinically available starting materials guiding future patient-specific studies of fertility disorders.
    Keywords:  PBMCs; X-chromosome inactivation; cumulus cells; hPGCLCs; hiPSC reprogramming; in vitro germ cell differentiation
    DOI:  https://doi.org/10.1093/biolre/ioag101
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