bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–06–14
thirteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. The post-reproductive ovary shifts from a reproductive to an immune-like organ.
  2. Two distinct causes contribute to the low efficiency of human pre-implantation development.
  3. Conserved RNA helicase Vasa regulates ribonucleoprotein condensate dynamics and mRNA localization.
  4. Genome integrity checkpoints in mammalian oogenesis.
  5. When Fertilization Is Not Enough: Maternal-Zygotic Transition as a Determinant of Embryo Competence in IVF.
  6. Proteomics-based insights into mammalian oocyte and early embryo development.
  7. The kinetochore component HCP-1 forms cytoplasmic granules in C. elegans germline.
  8. Transposable element regulation in mammalian germ cells and other contexts: multilayered repression, fertility, and regulated activation.
  9. Heterotypic intercellular adhesion tunes efficiency of cell-on-cell migration.
  10. AMPK tunes reproductive gene expression and small RNA homeostasis to mediate timely germ cell development.
  11. Somatic cells non-autonomously control germline incomplete cytokinesis through FGF signaling.
  12. Continuous modeling of primate embryogenesis from totipotency to early organogenesis.
  13. Gap junctions in the alimentary tract regulate reproductive span in C. elegans.
  1. Mol Hum Reprod. 2026 Jun 10. pii: gaag038. [Epub ahead of print]
    The post-reproductive ovary shifts from a reproductive to an immune-like organ.
    Aubrey Converse, Shweta S Dipali, Ian P Schowe, Emmett B Kelly, Shivani S Jambunathan, Sarah R Ocañas, Michael B Stout, Michele T Pritchard, Francesca E Duncan.
      Reproductive aging in females is characterized by the irreversible depletion of ovarian follicles, yet the structure and function of the post-reproductive ovary remain poorly defined. Using paired histological and bulk transcriptomic analyses of ovaries from reproductively young (2 m), reproductively old (18 m), and post-reproductive (24 m) mice, we mapped how ovarian identity evolves beyond follicle exhaustion. As expected, follicle loss, stromal remodeling, and increased collagen deposition were observed in the reproductively old and post-reproductive cohorts. Transcriptomic analyses revealed a shift from reproductive functionality to an immune-dominant signature with age. Correspondingly, post-reproductive ovaries exhibited increased infiltration of T cells, macrophages, and multinucleated giant cells. Although old and post-reproductive ovaries diverged substantially from young ovaries, they also showed discrete transcriptomic differences, indicating that the ovary continues to undergo molecular changes after reproductive senescence. Lastly, age-dependent changes in ovarian factors that are predicted to be secreted suggest that the post-reproductive ovary could be a source of pro-inflammatory signaling mediators with the potential to modulate extra-ovarian tissues. These findings challenge the assumption that the post-reproductive ovary is inert, instead indicating that it acquires an immune identity with potential endocrine and paracrine influence on whole-body aging.
    Keywords:  Menopause; fibrosis; inflammation; oopause; ovarian aging; ovary; post-reproductive; stroma
    DOI:  https://doi.org/10.1093/molehr/gaag038
  2. Cell. 2026 Jun 11. pii: S0092-8674(26)00637-9. [Epub ahead of print]
    Two distinct causes contribute to the low efficiency of human pre-implantation development.
    Zixuan Li, Lizhi Leng, Jinglei Zhai, Xiaowen Wang, Wuling Yang, Shuhui Wang, Haifeng Wan, Shuoping Zhang, Fei Gong, Xi Liao, Yuhui Li, Qing Zeng, Yansu Chen, Zhenyu Xiang, Feiyao Liu, Fuchu He, Yun Yang, Hongmei Wang, Xiaoming Xu, Ge Lin, Chun So.
      ∼50% of fertilized eggs arrest during human pre-implantation development, representing a major bottleneck for assisted reproductive technology. The underlying causes remain controversial. By imaging ∼150 live human and monkey fertilized eggs for up to 5 days, we uncovered that the second mitotic divisions are the most error-prone, accounting for early embryonic arrest. Stochastic centriole overduplication, which could be effectively suppressed by transient treatment with PLK4 inhibitor centrinone, predisposed 2-cell blastomeres to assembling multipolar spindles and missegregating chromosomes. Missegregated chromosomes in turn resulted in the formation of most micronuclei in human embryos and led to the arrest or death of daughter blastomeres. By contrast, late embryonic arrest was largely independent of chromosome missegregations but involved the activation of endoplasmic reticulum stress response, which could impair the expression of subsets of junctional and cell polarity proteins required for blastocyst formation. Thus, two distinct causes contribute to the low efficiency of human pre-implantation development.
    Keywords:  aneuploidy; centrosome; chromosome segregation; embryonic arrest; endoplasmic reticulum stress response; human embryo; long-term live-cell imaging; micronuclei; pre-implantation development; spindle
    DOI:  https://doi.org/10.1016/j.cell.2026.05.037
  3. iScience. 2026 Jun 19. 29(6): 116170
    Conserved RNA helicase Vasa regulates ribonucleoprotein condensate dynamics and mRNA localization.
    Siran Tian, Hyosik Kim, Harrison A Curnutte, Tatjana Trcek.
      Germ granules are germline ribonucleoprotein condensates that concentrate proteins and mRNAs essential for animal development. Although the DEAD-box RNA helicase Vasa is a conserved core germ granule component, its role within these condensates remains poorly understood. Using Drosophila and human cell systems, we showed that condensation of Oskar (Osk), the fly germ granule nucleator, occurred independently of Vasa. However, in late oocytes lacking Vasa, Osk-eGFP formed aggregates and exhibited markedly reduced exchange with the aggregate surroundings. Consistently, Vasa increased Osk-eGFP condensate recovery in cells. Additionally, mRNA localization to germ granules was not persistent in oocytes lacking Vasa, while in cells, co-expression of Vasa and Osk was necessary and sufficient for mRNA localization to condensates. Notably, localization of nanos messenger ribonucleoprotein (mRNP) to condensates reduced Vasa-dependent enhancement of Osk-eGFP exchange. Together, our study reveals the DEAD-box RNA helicase Vasa as a central regulator of condensate dynamics and mRNP localization in vivo and in cellulo.
    Keywords:  cell biology; molecular biology
    DOI:  https://doi.org/10.1016/j.isci.2026.116170
  4. Biol Reprod. 2026 Jun 11. pii: ioag118. [Epub ahead of print]
    Genome integrity checkpoints in mammalian oogenesis.
    John C Schimenti.
      Preserving chromosome integrity and minimizing mutations are crucial in the germline to prevent infertility, pregnancy loss and birth defects. This is particularly important in mammalian females, who reach puberty with a limited pool of oocytes and therefore have a finite reproductive lifespan. The most complex and genome-threatening stage of oogenesis is meiosis, during which homologous chromosomes pair and segregate at the first meiotic division. This process depends on the formation of hundreds of genetically programmed double-strand breaks (DSBs), which promote homologous recombination repair (HRR) and thereby drive homolog pairing and synapsis. Genetic studies in model organisms have revealed the existence of quality control mechanisms, or checkpoints, that detect unrepaired DNA damage or defective synapsis and, in mammals, eliminate defective oocytes from the ovarian reserve. After nearly three decades of study, a model has emerged in which the DNA damage and synapsis checkpoints share extensive mechanistic overlap. Several DNA repair proteins and damage sensors have been co-opted to recognize unsynapsed chromatin and transmit these signals through canonical DNA damage response pathways to well-known downstream effectors including TRP53 (p53) and TAp63 that trigger oocyte death. This review summarizes the key studies that have defined genetic quality control mechanisms that act before and during oogenesis, underscoring their relevance to infertility and reproductive aging.
    DOI:  https://doi.org/10.1093/biolre/ioag118
  5. Int J Mol Sci. 2026 May 26. pii: 4787. [Epub ahead of print]27(11):
    When Fertilization Is Not Enough: Maternal-Zygotic Transition as a Determinant of Embryo Competence in IVF.
    Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Ali Can Gunes, Aristotelis-Marios Koulakmanidis, Ioannis Papapanagiotou, Athanasios Karpouzos, Diamantis Athanasiou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Christina-Maria Trakatelli, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis, Georgios Daskalakis.
      A significant concern with IVF is that many embryos fail to develop despite proper fertilization. This gap indicates that factors outside sperm-oocyte fusion influence developmental competency. The maternal-zygotic transition (MZT) is a crucial developmental phase during which control shifts from maternally inherited transcripts to activation of the embryonic genome. During the early stages following fertilization, the embryo depends only on maternal mRNA and proteins amassed throughout oogenesis. For successful development, these transcripts must be expeditiously removed with the concurrent genome activation. Any disruption, whether due to inadequate maternal mRNA degradation, aberrant translational control, or delayed genome activation, has been associated with premature developmental stoppage and diminished blastocyst formation. Principal regulators, such as BTG4, CPEB1, DAZL, and components of the translational machinery, govern this modification and seem to be affected by the quality of the oocyte and the age of the mother. Increasing evidence suggests that disruption of MZT may account for instances of suboptimal embryo development that conventional assessment techniques cannot elucidate. MZT offers a biological framework for assessing embryo competency beyond simple appearance. If scientists had a deeper understanding of this process, they might identify molecular markers and enhance the selection of embryos in IVF.
    Keywords:  early embryogenesis; embryo arrest; embryo development; in vitro fertilization; maternal mRNA clearance; maternal-zygotic transition; oocyte competence; translational control; zygotic genome activation
    DOI:  https://doi.org/10.3390/ijms27114787
  6. Nat Cell Biol. 2026 Jun 11.
    Proteomics-based insights into mammalian oocyte and early embryo development.
    Sifan Rong, Zhuocheng Liu, Wencheng Zhu, Liangshan Mu.
      Advances in proteomics are transforming our understanding of mammalian oocyte maturation and preimplantation embryo development. These resources and their findings provide unprecedented insights into the molecular underpinnings of developmental competence. Here we summarize the ongoing development of proteomic methodologies and highlight the stage-specific reprogramming events of the proteome in both humans and mice, underscoring the unique utility of proteomics in deciphering oocyte maturation and early embryonic development. Furthermore, we discuss the clinical implications of these findings, highlighting the translational potential of proteomics in understanding reproductive ageing, improving oocyte quality, and refining the outcomes of assisted reproductive technology.
    DOI:  https://doi.org/10.1038/s41556-026-01993-x
  7. J Cell Sci. 2026 Jun 08. pii: jcs.264651. [Epub ahead of print]
    The kinetochore component HCP-1 forms cytoplasmic granules in C. elegans germline.
    Hannah L Hertz, Ian F Price, Wen Tang.
      The kinetochore is a multiprotein complex that assembles on centromeric chromatin and serves as the attachment site for spindle microtubules, thereby ensuring accurate chromosome segregation during cell division. Here we present evidence that kinetochore component HCP-1 forms distinct cytoplasmic foci in the C. elegans germline. Prior to cell division, HCP-1 localizes to the nuclear envelope of germ nuclei and forms granules that are distinct from germ granules. Upon mitotic entry, perinuclear HCP-1 is imported into the nucleus to facilitate chromosome segregation. We further show that HCP-1 associates with nuclear pore proteins (NPPs). Loss of NPP-14 disperses perinuclear HCP-1, impairs its nuclear import, and leads to defects in embryonic spindle assembly. Together, these findings provide new insights into the spatial regulation of HCP-1 and highlight a role for nuclear pore components in coordinating kinetochore assembly.
    Keywords:  Caenorhabditis elegans; Germ granules; Germline; Kinetochore; Nuclear pore complex
    DOI:  https://doi.org/10.1242/jcs.264651
  8. Epigenomics. 2026 Jun 10. 1-18
    Transposable element regulation in mammalian germ cells and other contexts: multilayered repression, fertility, and regulated activation.
    Peilin Li, Soichiro Yamanaka.
      Transposable elements (TEs), particularly retrotransposons that dominate mammalian genomes, are pervasive components of mammalian genomes whose activation is constrained by multilayered repression systems. In germ cells, this repression architecture is particularly elaborate, integrating chromatin-based silencing, DNA methylation, and small RNA-guided pathways to safeguard genome integrity during epigenetic reprogramming. These mechanisms are coordinated yet mechanistically specialized, targeting distinct phases of the transposon life cycle and different TE families across developmental stages. Yet the distinctive chromatin landscape of germ cells also creates windows of developmental permissiveness during which TE transcription can occur. Beyond the germline, TE expression can emerge in defined stages of early embryogenesis, extraembryonic development, neural differentiation, and aging, with consequences ranging from chromatin remodeling and regulatory co-option to inflammatory signaling and genome instability. Together, these observations raise a central question: how do different mammalian lineages balance epigenetic plasticity with genome defense? Here, we synthesize current understanding of the molecular logic of TE repression, emphasizing the germline, and integrate evidence across development and aging. We highlight shared principles-such as epigenetic permissiveness and RNA-guided targeting-while underscoring a key difference in regulatory outcome: somatic contexts may tolerate, co-opt, or pathologically amplify TE activity, whereas the germline converts transient activation into heritable, sequence-specific silencing.
    Keywords:  Transposon; chromatin remodeling; gametogenesis; genomic integrity; non-coding RNAs
    DOI:  https://doi.org/10.1080/17501911.2026.2685055
  9. Proc Natl Acad Sci U S A. 2026 Jun 16. 123(24): e2524496123
    Heterotypic intercellular adhesion tunes efficiency of cell-on-cell migration.
    Chandrashekar Kuyyamudi, Suhrid Ghosh, Cassandra G Extavour.
      Cell migration across epithelial barriers occurs in diverse developmental, immunological, and pathological contexts. Here, we investigate the contribution of heterotypic adhesion between migrating cells and epithelial "substrate" cells to transepithelial migration. Using an in silico model inspired by the migration of primordial germ cells across the midgut epithelium in the Drosophila embryo, we show that heterotypic adhesion modulates migration efficiency in a nonmonotonic manner, revealing the existence of an optimal adhesion regime. Consistent with this prediction, in vivo overexpression of E-cadherin in germ cells accelerated their exit from the midgut relative to controls. Beyond providing experimentally testable predictions, our model integrates and explains previous observations on the role of heterotypic adhesion in cell-on-cell migration, offering a framework for understanding transepithelial migration across biological contexts.
    Keywords:  Cellular Potts model; CompuCell3D; E-cadherin; germ cell migration; intercellular adhesion
    DOI:  https://doi.org/10.1073/pnas.2524496123
  10. Nucleic Acids Res. 2026 Jun 08. pii: gkag555. [Epub ahead of print]54(11):
    AMPK tunes reproductive gene expression and small RNA homeostasis to mediate timely germ cell development.
    Sabih Rashid, Fabian Braukmann, Eric A Miska, Richard Roy.
      Developmental plasticity allows organisms to adapt to environmental stressors and improve fitness. Caenorhabditis elegans can enter an alternative larval stage, the dauer, marked by developmental quiescence and complete transcriptomic remodeling. The energy modulator AMPK is required for animals to passage through dauer while preserving germline quiescence. Without AMPK, dauer animals exhibit reproductive defects, which are partially suppressed by disabling small RNA pathway components. To understand how the loss of AMPK affects RNA homeostasis and gene expression, we performed transcriptomic analysis of AMPK mutants. We reveal that over 60% of the C. elegans genes are affected by the loss of AMPK during the dauer stage. This is accompanied by a widespread increase in reproductive gene expression in dauer, as well as the upregulation of most small RNAs and small RNA pathway components, particularly the spermatogenic Argonautes ALG-3/4. Eliminating ALG-3/4 corrects several reproductive defects, including premature dauer spermatogenesis, and partially restores fertility. Notably, decreasing global small RNA biogenesis also partially corrects these phenotypes, possibly by destabilizing their associated Argonaute effectors. Our work highlights a role for AMPK in the temporal regulation of small RNA populations to establish a delicate balance that is essential for reproductive fitness following quiescence during periods of stress.
    DOI:  https://doi.org/10.1093/nar/gkag555
  11. bioRxiv. 2026 Jun 06. pii: 2026.06.04.729929. [Epub ahead of print]
    Somatic cells non-autonomously control germline incomplete cytokinesis through FGF signaling.
    Beth Kern, Zachary Y Berkley, Samuel Price, Kari F Lenhart.
      Across species, germ cells divide and differentiate as interconnected units, termed cysts. These cysts are generated through reiterative rounds of mitosis followed by incomplete cytokinesis to generate stable ring canals (RCs). Despite the ubiquity of germ cell incomplete cytokinesis, it is still unclear how this program is mechanistically regulated across multiple cell cycles to retain integrity of the cyst. Here, by leveraging longitudinal live imaging of the Drosophila testis we have identified a critical, non-autonomous role for somatic support cells in maintenance of germline RC stability. We find that F-actin at RCs is stable throughout interphase but is dynamically disassembled and reassembled at each reiterative mitotic entrance and exit. Importantly, we find that somatic cells regulate the stability of interphase RC F-actin through the secreted growth factor, FGF. Genetic or pharmacological inhibition of FGF signaling induces disassembly of RC F-actin during interphase. Persistent clearance of F-actin from the RC leads to failure of incomplete cytokinesis and cyst abscission, suggesting that stable F-actin at RCs is required for the robust maintenance of incomplete cytokinesis through multiple rounds of germ cell divisions. Finally, we mechanistically link FGF signaling to germline activity of the non-receptor tyrosine kinase, Src64, which is known to regulate RC F-actin through Arp2/3. Taken together, we find a previously unappreciated role for somatic support cells in controlling an essential aspect of germ cell biology in the mitotically dividing spermatogonial pool.
    Summary Statement: Somatic cells of the gonad secrete FGF ligand, Pyramus, which is required for maintenance of F-actin at germline ring canals and integrity of germline incomplete cytokinesis.
    DOI:  https://doi.org/10.64898/2026.06.04.729929
  12. Cell. 2026 Jun 10. pii: S0092-8674(26)00582-9. [Epub ahead of print]
    Continuous modeling of primate embryogenesis from totipotency to early organogenesis.
    Wei Zheng, Bing Peng, Zilin Chen, Kangwei Huang, Yueyao Qi, Huimin Niu, Hui Shen, Jun Wu, Jianwei Jiao, Peng Du.
      Embryo-like structures, or embryoids, are powerful models to investigate early embryonic development. Yet, previous models cover only partial developmental stages, restricting their applications. Here, we successfully generate primate organogenetic embryoids from cynomolgus totipotent blastomere-like stem cells (cTBLCs). cTBLCs, reprogrammed from pluripotent stem cells and stably maintained, can display key totipotent-like molecular and functional features resembling zygotes/2-4-cell blastomeres. cTBLCs spontaneously generate well-organized blastoids that further progress through gastrulation to early organogenesis, thus exhibiting neural-tube-like structures and cardiac-like beating activity. Using single-cell RNA sequencing (scRNA-seq), we visualized stepwise cell-state transitions from cTBLCs to organogenetic lineages and identified an intermediate 8-cell/morula-like state. Interestingly, we uncovered a dynamic cascade of regulatory networks originating from cTBLCs, which represented an intrinsic developmental initiation program occurring independently of classical fertilization-associated events. Together, the cTBLC platform provides a unified in vitro framework to investigate developmental initiation, early lineage specification, and organogenesis.
    Keywords:  beating heart; blastoid; cell-fate determination; embryo-like structures; embryogenesis; gastrulation; organogenesis; primate; stem-cell-derived embryo model; totipotent blastomere-like cells
    DOI:  https://doi.org/10.1016/j.cell.2026.05.023
  13. bioRxiv. 2026 Jun 07. pii: 2026.06.03.729750. [Epub ahead of print]
    Gap junctions in the alimentary tract regulate reproductive span in C. elegans.
    Hitomi Hidaka, Kazuma Akashi, Shiying Wang, Shohei Yamamoto, Takumi Chinen, Shoji Hata, Masamitsu Fukuyama, Daiju Kitagawa.
      Aging does not occur uniformly throughout an organism but is instead differentially regulated across distinct physiological systems. In particular, reproductive aging is often temporally distinct from somatic aging and exhibits species-specific trajectories, suggesting that different physiological functions may age independently. Here we show that mutation of inx-20, an innexin family gene encoding a gap junction component, markedly extends reproductive span, with only a minor increase in overall lifespan. Furthermore, this extension of reproductive span persists in a feminized genetic background, thereby precluding the possibility that it is driven by altered sperm dynamics. inx-20 is expressed in a specific subset of cells within the alimentary tract, and its expression is selectively repressed in a fraction of these cells during dauer diapause, suggesting a role in nutrient responses. Genetic analyses suggest that inx-20 operates via a distinct mechanism that does not intersect with the TGF-beta and IIS-FOXO pathways, which are established regulators of reproductive span. Collectively, our results suggest that gap junctions in the alimentary tract are a selective determinant of reproductive span, capable of extending it substantially without a commensurate effect on lifespan.
    DOI:  https://doi.org/10.64898/2026.06.03.729750
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