bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–04–26
eleven papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Dynamic blebbing and absence of organelle transfer during mouse oocyte formation.
  2. Visualizing Zygotic Genome Activation In Single Cells of Early Embryos.
  3. A Nanos3-containing protein complex can activate RNA translation in primordial germ cells in vivo.
  4. Complementary volume electron microscopy-based approaches reveal ultrastructural changes in germline intercellular bridges.
  5. Zona pellucida is required for oocyte actin cortex and oocyte-somatic cell interactions during oocyte growth.
  6. Wnt4 as a signal coordinates DNA methylation and acetylation to determine germ line fate.
  7. Oocyte-specific acylglycerol kinase loss leads to infertility in mice via mitochondrial dysfunction.
  8. The reprogramming and function of H4K20me1 during early embryo development.
  9. Functional requirement for Dicer helicase arginine methylation in 26 G siRNA biogenesis and oocyte meiotic program.
  10. The proteomic landscape and temporal dynamics of human and mouse gastruloid development.
  11. Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.
  1. EMBO J. 2026 Apr 21.
    Dynamic blebbing and absence of organelle transfer during mouse oocyte formation.
    Eishi Aizawa, So Shimamoto, Eriko Kajikawa, Junko Hara, Takaya Abe, Hiroki Shibuya, Tomoya S Kitajima.
      Oocyte formation in mammals is a tightly regulated process essential for female fertility, yet the underlying mechanisms remain poorly understood. In this study, we establish an ex vivo culture system that faithfully recapitulates in vivo development and enables long-term live imaging of mouse fetal ovaries. Using high resolution imaging, we capture the dynamic behaviors of germ cells during the development from oogonia to nascent oocytes. We identify pronounced blebbing activity during the mitosis-to-meiosis transition. This behavior is regulated by meiotic initiation signals, underscoring its potential developmental relevance, although its precise role remains unclear. A prevailing model suggests that oocyte formation involves organelle transfer from neighboring germ cells during cyst breakdown. However, through photoconversion-based tracking, we observe no detectable transfer of mitochondria or centrosomes, as organelles remain confined to individual cells. These findings point to alternative mechanisms for cytoplasmic enrichment in oocytes. Our study provides new insights into mammalian oocyte formation and establishes a powerful platform for analyzing germ cell dynamics in real time.
    DOI:  https://doi.org/10.1038/s44318-026-00780-6
  2. J Vis Exp. 2026 Apr 03.
    Visualizing Zygotic Genome Activation In Single Cells of Early Embryos.
    Chuan Qin, Hui Chen.
      Early embryogenesis requires the maternal-to-zygotic transition (MZT) that necessitates the zygotic genome activation (ZGA). During ZGA, hundreds to thousands of genes are transcribed, which is essential for various processes in early embryo development, including maintaining embryonic survival, cell fate specification, and germ layer formation. One major challenge in studying ZGA has been to directly visualize ZGA in individual cells of early embryos. Here, we describe a method to directly visualize ZGA in single cells of early embryos by metabolic labeling of nascent transcripts using 5-ethynyl uridine (5-EU), followed by conjugating the nascent EU-RNAs with fluorophores via click chemistry and visualizing them in whole-mount embryos by confocal microscopy, using Xenopus laevis as a model. This method enabled us to track single-cell ZGA in whole-mount embryos and to reveal the heterogeneous onset of ZGA in space and time during early embryogenesis. It can be used in other embryonic systems or tissues to study gene transcription and genome regulation at the single-cell level.
    DOI:  https://doi.org/10.3791/70592
  3. EMBO Rep. 2026 Apr 24.
    A Nanos3-containing protein complex can activate RNA translation in primordial germ cells in vivo.
    Antra Gupta, Arzu Melsa Basaran, Moritz Ophaus, Shantanu Madiwale, Martin Stehling, Michal Reichman-Fried, Katsiaryna Tarbashevich, Erez Raz.
      Maintaining the germline fate requires tight post-transcriptional control of RNA function. Here, we investigate how primordial germ cell (PGC) identity is maintained in zebrafish and reveal that the conserved RNA-binding proteins Nanos3 and Dead End1 form a complex that safeguards PGC identity. Using transcriptomics and in vivo imaging-based analyses, we show that this complex controls the translational activation and localization of both nanos3 and dead end1 RNAs, establishing a positive feedback loop crucial for regulating their protein expression. These findings uncover a previously unknown layer of control over germline development, where a complex containing Nanos3, a protein associated with the inhibition of RNA translation, acts as an activator by interacting with an eIF3 complex protein to promote translation, thereby maintaining specific RNAs at the periphery of phase-separated germ cell granules. Disrupting the physical interaction between Nanos3 and Dead End1 leads to transdifferentiation of germ cells into somatic lineages. Overall, our findings identify a self-sustaining mechanism of translational activation in vivo, positioning the Nanos3-Dead End1 complex as a central effector of germline fate.
    DOI:  https://doi.org/10.1038/s44319-026-00781-w
  4. J Cell Sci. 2026 Apr 22. pii: jcs.264713. [Epub ahead of print]
    Complementary volume electron microscopy-based approaches reveal ultrastructural changes in germline intercellular bridges.
    Irina Kolotuev, Sophie Khazanov, Abigayle Williams, Caroline Kizilyaprak, Stephanie Pellegrino, Lindsay Lewellyn.
      The Drosophila melanogaster egg chamber is a powerful model system to study germline intercellular bridges, or ring canals, which connect the developing oocyte to supporting nurse cells. Despite their importance, it is technically difficult to use electron microscopy (EM)-based approaches to monitor changes in ring canal structure. Here, we utilize of a complementary set of volume EM-based approaches to visualize ultrastructural changes in the germline ring canals. The combination of array tomography and focused ion beam scanning electron microscopy provided insight into previously unappreciated aspects of ring canal structure. We quantified differences in ring canal size and thickness within and between germline cell clusters and visualized the formation of membrane interdigitations near the ring canals much earlier than previously reported. Reconstruction of multiple egg chambers provided insight into the 3D orientation of these extensive cell-cell contacts. Finally, we identified a novel membrane structure that appeared to line the interior of the ring canal lumen. This imaging framework could be applied to other tissues with technical challenges, where the small structure of interest is located within a large sample volume.
    Keywords:  Drosophila melanogaster; Egg chamber; Intercellular bridge; Ring canal; Volume electron microscopy
    DOI:  https://doi.org/10.1242/jcs.264713
  5. Cell Death Discov. 2026 Apr 20.
    Zona pellucida is required for oocyte actin cortex and oocyte-somatic cell interactions during oocyte growth.
    Shoujing Liang, Weixi Xiang, Ruping Quan, Jiayu Su, Chao Lv, Hualin Huang, Hongmei Xiao.
      Structural defects in the zona pellucida (ZP), caused by mutations in ZP genes, are a recognized cause of female infertility; however, their pathogenic mechanisms are not fully understood. Here, we investigated how two distinct ZP defects (complete absence and thinning) compromise fertility using Zp1mut/mut and Zp2mut/mut rat models. We found that ZP deficiency leads to stage-specific oocyte loss during early antral follicle development in vivo and arrests the maturation of fully grown oocytes in vitro, which also exhibit reduced diameter and mitochondrial dysfunction. From the secondary follicle stage onward, granulosa cells showed reduced proliferation, increased apoptosis, and impaired adhesion, culminating in a disorganized cumulus-oocyte complex morphology and disrupted steroidogenesis by the antral stage. Further analysis revealed that the specialized structures for oocyte-somatic cell interaction, namely transzonal projections and oocyte microvilli, were disorganized and reduced in number. This structural disruption was accompanied by a global perturbation of the bidirectional communication and physical adhesion network between the oocyte and its somatic niche, underscoring the ZP's essential role in organizing this functional microenvironment. At the molecular level, single-cell transcriptomic and protein analyses demonstrated that ZP deficiency induces a thinning of the oocyte cortical actin layer and dysregulation of cytoskeletal dynamics. This was associated with an upregulation of actin-regulating proteins, including TPM4 and ACTN1, and the engagement of focal adhesion-related pathways. The observed cortical actin disorganization provides a plausible mechanistic link to the concurrent abnormalities in microvilli and cell-cell adhesion. Collectively, our results establish the ZP as a critical structural scaffold that ensures oocyte cortical integrity and coordinates the surrounding somatic cell niche. Its disruption leads to a progressive failure in oocyte-somatic cell interaction and support, ultimately resulting in oocyte developmental impairment and loss. This study provides detailed mechanistic insights into the pathogenesis of ZP-related female infertility (particularly empty follicle syndrome).
    DOI:  https://doi.org/10.1038/s41420-026-03124-9
  6. Dev Biol. 2026 Apr 22. pii: S0012-1606(26)00096-5. [Epub ahead of print]
    Wnt4 as a signal coordinates DNA methylation and acetylation to determine germ line fate.
    Florence Naillat, Shin-Ichi Tomizawa, Elena Ivanova, Gavin Kelsey, Seppo J Vainio.
      Wnt4 signaling promotes somatic cell development in the female embryo, but its role in germline differentiation during meiosis remains poorly characterized. To explore Wnt4 functions in female embryonic gonads, we isolated germ cells from Wnt4 knock-out mice to investigate histone modifications and DNA methylation distribution patterns. The lack of the Wnt4 signaling pathway deregulates germ cell cycle markers, such as cyclins, alters the cell cycle by impairing meiosis progression, maintains the germ cells in the G1-GO and S phases, and supporting DNMT3A and DNMT1 enzyme expression at meiosis entry. Conversely, in the nucleus of the Wnt4 knock-out female germ cells, an increase of H3K27me3 pattern persists at the entry of meiosis, leading to altered methylation at the Sycp3 promoters combined with an acetylation of Stra8 promoter at E14.5. This changed pattern might be explained by the overexpression of Creb-binding protein (CBP) in the mutant female germ cells, leading to deregulation of histone marks on meiosis genes. Our findings reveal that the Wnt4 signal is necessary for inducing meiosis by inhibiting germ cell proliferation via the regulation of histone modification. Wnt4 signaling plays a crucial role in regulating the delicate balance between DNA methylation and acetylation in female germ cells. This fascinating interaction highlights the complexities of cellular processes that contribute to reproductive health and development.
    Keywords:  CBP; DNA methylation; DNMT; H3K27Ac; H3K27me3; Wnt4; germ cells; meiosis; p300; transcription
    DOI:  https://doi.org/10.1016/j.ydbio.2026.04.015
  7. Commun Biol. 2026 Apr 23.
    Oocyte-specific acylglycerol kinase loss leads to infertility in mice via mitochondrial dysfunction.
    Tingting Lu, Yanquan Li, Fanghao Guo, Chunhua Tang, Shiyi Zhu, Jin Dong, Ping Zhang, Ningling Wang, Wen Li, Yuchuan Zhou.
      The orderly architecture and energy supply of mitochondria, orchestrated by proteins, are essential for oocyte maturation. Acylglycerol kinase (AGK) is known to predominantly localize to the mitochondrial membrane and regulate multiple cellular processes related to Sengers syndrome and tumorigenesis. However, the functions of AGK in the ovaries remain largely unknown. Here, we generate mice with oocyte-specific disruption of Agk. Ablation of Agk in oocytes causes ovarian atrophy characterized by the arrest of early secondary follicles and a significantly reduced number of mature follicles, ultimately leading to female sterility. Furthermore, mitochondria in Agk-deficient oocytes exhibit significant structural and organizational defects. The developmental competence of Agk-deficient oocytes is compromised with decreased mitochondrial membrane potential, reduced mtDNA copy number, impaired ATP synthesis, and elevated reactive oxygen species. Mechanistically, single-cell RNA sequencing shows that genes associated with the mitochondrial oxidative phosphorylation (OXPHOS) pathway are among the most significantly downregulated in Agk-disrupted oocytes. Spatial metabolomics further identifies a substantial reduction in phosphate-associated metabolites linked to the OXPHOS pathway in Agk-deficient oocytes. These findings demonstrate that AGK plays an essential role in oocyte development and folliculogenesis by maintaining mitochondrial function. The present study identifies AGK as a potential diagnostic marker and therapeutic target for female infertility.
    DOI:  https://doi.org/10.1038/s42003-026-10073-7
  8. EMBO Rep. 2026 Apr 22.
    The reprogramming and function of H4K20me1 during early embryo development.
    Xiangrui Meng, Zhen He, Dong Fang, Wenbo Li, Jia Guo, Jiacheng Lu, Fen Yan, Xin Dong, Lingling Chen, Sarmir Khan, Chunling Wang, Jiawei Xu.
      Histone modifications play critical roles in regulating chromatin dynamics and embryonic development. Among these, histone H4 lysine 20 mono-methylation (H4K20me1) is an essential epigenetic mark associated with gene expression and genome stability. However, the reprogramming and functional roles of H4K20me1 in early embryogenesis remain unclear. Here, we map genome-wide distributions of H4K20me1 in mouse, human, and zebrafish early embryos, revealing a broad distribution pattern along with species-specific features. H4K20me1 is predominantly enriched in gene bodies and undergoes dynamic erasure and reestablishment following fertilization. Functional perturbation of SET8, the only known H4K20me1 methyltransferase, results in developmental arrest, highlighting its necessity for embryogenesis. Mechanistically, H4K20me1 is crucial for zygotic genome activation (ZGA), where it regulates RNA synthesis and transcription, and promotes chromatin accessibility. Our findings provide insights into the dynamic reprogramming and regulatory functions of H4K20me1 in early developmental processes.
    DOI:  https://doi.org/10.1038/s44319-026-00780-x
  9. Nat Commun. 2026 Apr 21.
    Functional requirement for Dicer helicase arginine methylation in 26 G siRNA biogenesis and oocyte meiotic program.
    Nick Newkirk, Shin-Yu Chen, Tokiko Furuta, Kenneth A Trimmer, Leilei Shi, Sabrina Stratton, Hongyuan Li, Xiaodong Cheng, Mark T Bedford, Swathi Arur.
      Spatiotemporal regulation of Dicer is essential for small RNA biogenesis and fertility, yet how its helicase domain is controlled remains unclear. Using Caenorhabditis elegans, we identify a regulatory role for the arginine-rich GRARR motif within helicase domain motif VI of DCR-1. Mutating conserved arginines in this sequence disrupts maternal 26 G endo-siRNA production, impairs oocyte meiosis I and II, and reduces fertility. Biochemically, an asymmetrically dimethylated DCR-1 GRA[R495*]R peptide enhances interaction with ERI-5, a tandem-Tudor protein in the ERIC complex, while loss of DCR-1(R495) diminishes this interaction in vivo. Genetically, eri-5 deletion phenocopies the dcr-1 R495K mutant, supporting a functional partnership in 26 G siRNA biogenesis. Notably, these defects parallel those seen in DCR-1 phosphorylation mutants in the catalytic domain. AlphaFold modeling suggests that arginine methylation in the helicase domain and serine phosphorylation in catalytic domain may operate in a coordinated manner to modulate DCR-1 conformation, effector recruitment, and proper execution of the oocyte meiotic program.
    DOI:  https://doi.org/10.1038/s41467-026-72069-5
  10. Nat Cell Biol. 2026 Apr 24.
    The proteomic landscape and temporal dynamics of human and mouse gastruloid development.
    Riddhiman K Garge, Valerie Lynch, Rose Fields, Silvia Casadei, Sabrina Best, Jeremy Stone, Matthew Snyder, Connor Kubo, Arata Wakimoto, Zukai Liu, Chris D McGann, Jay Shendure, Lea M Starita, Nobuhiko Hamazaki, Devin K Schweppe.
      The embryo establishes a body plan and primes itself for organogenesis during gastrulation. As gastrulation is challenging to study in vivo, stem-cell-derived 'gastruloids' have emerged as powerful surrogates. Although transcriptomics and imaging have been applied extensively to such embryo models, the dynamics of their proteomes remains largely unknown. Here we apply quantitative proteomics to human and mouse gastruloids at four key stages. We leverage these data to map the expression dynamics of protein complexes, and to nominate cooperative proteins. With matched transcriptome data, we investigate global and stage-specific discordance between the transcriptome and proteome and leverage phosphosite dynamics to nominate kinase-substrate relationships. Finally, we apply co-regulation network analysis to identify genes linked to the Commander complex, the perturbation of which leads to morphological defects in gastruloids. Altogether, our work showcases the potential of applying proteomics to embryo models to advance our understanding of mammalian development in ways challenging through transcriptomics alone.
    DOI:  https://doi.org/10.1038/s41556-026-01937-5
  11. Nat Genet. 2026 Apr 23.
    Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome.
    Genes and Health Research Team
      Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.
    DOI:  https://doi.org/10.1038/s41588-026-02543-9
This page is being maintained by Thomas Krichel. It was last updated on 2026‒04‒26 at 9:06.