bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–11–01
ten papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Oocyte-specific OMC1 is required for maintaining chromosome cohesion through reproductive life.
  2. Mitochondrial amino acid export preserves mitochondrial volume at the egg-to-embryo transition.
  3. Polarization of the Drosophila oocyte by active cortical exchange.
  4. Proteomic and transcriptomic analysis reveals an intracellular role for zona pellucida protein 2 in mouse morula-blastocyst transition.
  5. Protocol for visualizing microtubules in transzonal projections of mouse ovarian follicles.
  6. Slender lobes is a spindle matrix protein regulated by spindle envelope kinase Greatwall in oocytes.
  7. Spatio-temporally regulated maternal RNA decay factor essential for zebrafish development.
  8. Organelle Volume Facilitates Spindle Positioning During C. elegans Female Meiosis.
  9. CYB-4/CDK-1 coordinates timing of meiotic entry, chromosome morphogenesis and oocyte maturation in C. elegans.
  10. A premature ovarian insufficiency-associated LMD-3 point mutation impairs protein stability and causes autophagic-lysosomal dysfunction in Caenorhabditis elegans.
  1. Nat Aging. 2026 Oct 29.
    Oocyte-specific OMC1 is required for maintaining chromosome cohesion through reproductive life.
    Sakie Iisaka, Shuhei Yoshida, Ryuki Shimada, Tappei Mishina, Sayoko Fujimura, Manami Koshiguchi, Ryuichi Kimura, Shinya Oki, Kimi Araki, Tomoya S Kitajima, Kei-Ichiro Ishiguro.
      In mammals, oocytes initiate meiosis during fetal development and then enter a prolonged meiotic arrest. During this female-specific long-term arrest, chromosome cohesion mediated by nonrenewable REC8 cohesin gradually deteriorates, predisposing oocytes to age-associated chromosome segregation errors when meiosis resumes for maturation in adulthood. Female-specific factors that counteract this deterioration remain unknown. Here we identify OMC1 as an oocyte-specific chromosomal protein required for the maintenance of chromosome cohesion through reproductive life. OMC1 associates with REC8-cohesin-containing chromosome axes from fetal stages through adult meiotic maturation. Using Omc1 knockout mice, we show that OMC1 is required for cohesin maintenance until completion of meiotic maturation, thereby suppressing age-associated chromosome segregation errors. These findings provide insight into the female germ-cell-intrinsic molecular basis that supports reproductive longevity by suppressing age-associated chromosome cohesion loss, which leads to egg aneuploidy, a major cause of infertility and congenital disorders.
    DOI:  https://doi.org/10.1038/s43587-026-01245-5
  2. bioRxiv. 2026 Oct 09. pii: 2026.10.08.757432. [Epub ahead of print]
    Mitochondrial amino acid export preserves mitochondrial volume at the egg-to-embryo transition.
    Melissa C Pamula, Lauren Clamon, Samuel Block, Suzanne Savage, Christoph Gaebelein, Ashid Amarsanaa, Margaret E Bisher, David Mankus, Abigail Kr Lytton-Jean, Nora Kory, Ruth Lehmann.
      In animals, the transition from egg to embryo marks a rapid shift in cellular physiology, yet how mitochondria adapt to support this conversion remains poorly understood. We performed a targeted RNAi screen of conserved, nuclear-encoded mitochondrial proteins in Drosophila melanogaster to identify maternal effects. We identified distinct phenotypic classes affecting mitochondrial distribution or morphology in early embryos. We focused on Sideroflexin-1/3 (Sfxn1-3), a conserved mitochondrial inner membrane transporter, because it uniquely affects embryonic mitochondrial morphology. Maternal loss of Sfxn1-3 causes striking mitochondrial enlargement in embryos but not in oocytes, placing the trigger at the egg-to-embryo transition. Combining mitochondrial immunopurification with LC/MS-based metabolomic profiling, we show that amino acids are markedly enriched in Sfxn1-3-deficient mitochondria in both oocytes and embryos. This accumulation developmentally uncouples the metabolic and morphological phenotypes. By selectively disrupting discrete steps of egg activation, including translational activation, cell cycle re-entry, and fertilization, we demonstrate that mitochondrial swelling is independent of each, prompted instead by egg hydration. Beyond its reported role in proliferating cells as a serine importer, our data support a role for germline Sfxn1-3 in regulating inner mitochondrial membrane permeability to osmotically active amino acids. This activity is crucial for preserving organelle volume during the osmotic challenge of oocyte hydration. When this export fails, amino acid accumulation amplifies osmotic stress and drives rapid mitochondrial swelling. Together, these findings identify mitochondrial inner membrane permeability to amino acids as a key regulatory step that couples pre-established metabolite compartmentalization to osmotic adaptation at egg activation, and reveal how mitochondrial metabolic integrity and volume control are coordinated at this critical developmental transition.
    DOI:  https://doi.org/10.64898/2026.10.08.757432
  3. ArXiv. 2026 Oct 07. pii: arXiv:2610.10916v1. [Epub ahead of print]
    Polarization of the Drosophila oocyte by active cortical exchange.
    Mohammadhossein Firouznia, Wen Lu, Margot Lakonishok, Reza Farhadifar, Vladimir I Gelfand, Michael J Shelley.
      Anterior-posterior polarization in the Drosophila oocyte requires posterior localization of oskar mRNA. oskar mRNA is produced in the anteriorly situated nurse cells, moved into the oocyte, and assembled into oskar-Staufen ribonucleoprotein particles (RNPs). These RNPs then move through the oocyte and interact with the cortex, where myosin-V binds them to the actin network and kinesin-1 removes them along cortically anchored microtubules. This cortical tug-of-war takes place against an anterior-to-posterior decrease in microtubule density. How the interplay between cytoplasmic transport and cortical binding and unbinding produces a stable posterior cap is unclear. Here, we combine quantitative microscopy, photoconversion experiments, experimental perturbations, and biophysical modeling to show that posterior localization emerges from position-dependent cortical exchange coupled to cytoplasmic diffusion. Our model, which accounts for the tendency of RNPs to demix, suggests that two key parameters that determine the observed localization pattern are the total amount of oskar and the ratio of cortical unbinding to binding rates (the exchange equilibrium constant). Given oskar volume fractions in wild-type, the measured exchange constant is such that oskar localizes to the posterior cortex without demixing. If the balance is broken, say by increasing unbinding rates, oskar irreversibly demixes into cytoplasmic droplets. This is consistent with observations from our experimental perturbations. Our results show how bulk diffusion and cortical exchange, in the face of oskar RNPs' self-attraction, convert a cytoskeletal asymmetry into robust developmental polarity.
    Keywords:  Drosophila oogenesis; cortical exchange kinetics; mRNA localization; phase separation
  4. BMC Genomics. 2026 Oct 22. pii: 885. [Epub ahead of print]27(1):
    Proteomic and transcriptomic analysis reveals an intracellular role for zona pellucida protein 2 in mouse morula-blastocyst transition.
    Thomas Nolte, Steffen Israel, Hannes C A Drexler, Georg Fuellen, Julina Wiese, Michele Boiani.
       BACKGROUND: Since the first description in 1827, the zona pellucida (ZP) has been viewed as an extracellular structure surrounding mammalian oocytes, with three canonical roles: encasement of the oocyte in the follicle, sperm binding at fertilization, and physical protection of the early embryo. However, over the past 10 years, mass spectrometry analyses in this laboratory have repeatedly and consistently detected abundant ZP proteins inside mouse embryos. Therefore, this study investigated whether ZP2, the most abundant of the ZP proteins, might also serve non-canonical functions that operate from inside the embryo rather than from the outside.
    RESULTS: Using mass spectrometry and monoclonal immunofluorescence, an intracellular fraction of ZP2 was found to persist throughout preimplantation mouse development, being among the most abundant proteins of the embryo. Intracellular ZP2 underwent an apparent increase at the 8-cell to morula stage rather than the monotonic decline expected of a passive maternal legacy. Basic colocalization analysis showed that part of this intracellular pool overlapped neither the cis-Golgi marker GM130 nor the endoplasmic reticulum marker Calreticulin, identifying a non-Golgi, non-ER intracellular ZP2 fraction. Consistent with this, ZP2 was susceptible to Trim-Away mediated depletion, which typically can act on a protein only if this is cytosolically accessible. Although ZP2 depletion stalled at approximately 50% due to the enormous abundance of ZP2, this partial knockdown delayed the morula-to-blastocyst transition and produced blastocysts with reduced trophectoderm and primitive endoderm and impaired postimplantation development in vitro and in vivo. These effects were specific to ZP2, as they did not occur when Trim-Away was redirected to an irrelevant target. Proteome and transcriptome analyses of ZP2 knockdown embryos returned overrepresented gene ontology terms related to cytoplasmic translation in the proteome, which was confirmed by an O-propargyl-puromycin incorporation assay; and to endoderm development and gastrulation in the transcriptome, which provide a coherent molecular correlate of the morula retardation phenotype.
    CONCLUSIONS: These results confer ZP2 with hitherto unsuspected intracellular roles during embryogenesis in the mouse model of human reproduction. ZP2 can therefore no longer be referred to as a solely extracellular-operating, oocyte-specific gene product.
    Keywords:   Trim-Away ; Animal model; Embryo development; Morpholino; Oocyte; Proteomics; RNA-seq; ZP2; Zona pellucida
    DOI:  https://doi.org/10.1186/s12864-026-13487-z
  5. STAR Protoc. 2026 Oct 28. pii: S2666-1667(26)00577-0. [Epub ahead of print]7(4): 104924
    Protocol for visualizing microtubules in transzonal projections of mouse ovarian follicles.
    Takao Tsurumaki, Akihiro Aikawa, Masamitsu Sato, Mika Toya.
      Visualizing microtubules within tissues remains technically challenging, limiting our understanding of their organization and function in vivo. Here, we present a protocol for visualizing microtubules in transzonal projections (TZPs), cellular projections that connect ovarian somatic cells and oocytes within mouse ovarian follicles. We describe steps and conditions for ovarian fixation, cryosection preparation, and immunostaining to preserve fine microtubule structures. We then detail procedures for super-resolution imaging to visualize fine microtubules within TZPs. For complete details on the use and execution of this protocol, please refer to Aikawa et al.1.
    Keywords:  Cell Biology; Cell-based Assays; Microscopy
    DOI:  https://doi.org/10.1016/j.xpro.2026.104924
  6. J Cell Biol. 2027 Jan 04. pii: e202606020. [Epub ahead of print]226(1):
    Slender lobes is a spindle matrix protein regulated by spindle envelope kinase Greatwall in oocytes.
    Rayane Kaade, Emma Peat, Charlotte Repton, Julia Niziol, Carmela Silva Mason, Li Ern Yap, Gera Pavlova, Hiroyuki Ohkura.
      Chromosome segregation is mediated by microtubule-based machinery, the spindle. Microtubule-independent structures, often called the spindle matrix or the spindle envelope, have been reported to embed or surround the spindle, respectively. The concepts have been around for several decades, but they still remain enigmatic. Here, we show the spindle matrix and the spindle envelope form one functional unit crucial for spindle structure and function in oocytes. We found that in Drosophila oocytes, Slender lobes (Sle) protein is an integral component of the spindle matrix, which has a composition different from that in mitotic cells. We further found that Greatwall (Gwl) kinase localizes to the spindle envelope tightly surrounding the Sle spindle matrix in oocytes. Gwl promotes assembly of the Sle spindle matrix, which in turn determines the location of the Gwl spindle envelope. sle silencing in oocytes resulted in spindle abnormalities. Cosilencing experiments revealed that Sle buffers the impacts of compromised kinetochore-microtubule interaction on centromere bi-orientation in meiotic metaphase I.
    DOI:  https://doi.org/10.1083/jcb.202606020
  7. bioRxiv. 2026 Aug 31. pii: 2026.08.20.745964. [Epub ahead of print]
    Spatio-temporally regulated maternal RNA decay factor essential for zebrafish development.
    Gopal Kushawah, Victor Daniel Aldas Bulos, Danielson Baia Amaral, Huzaifa Hassan, Stephanie H Nowotarski, Ariel A Bazzini.
      Maternal mRNA decay is essential for the Maternal-to-Zygotic Transition (MZT), yet its impact on spatial regulation has remained largely unexplored. We identify Cth1 as the first maternally encoded RNA-decay factor regulated in a spatiotemporal manner outside the germline in zebrafish, driven by conserved 3'UTR cis-elements. RfxCas13d-mediated depletion of maternal cth1 revealed early developmental defects that could not be assessed with SpyCas9 mutants due to infertility from impaired gametogenesis. Mechanistically, Cth1 acts independently of zygotic genome activation, recognizing AU-rich motifs in maternal 3'UTRs to promote deadenylation and decay in a spatio-temporal manner; deletion of these motifs or depletion of Cth1 stabilizes both reporter and endogenous transcripts. These findings establish Cth1 as a key component of the maternal program and provide the first direct evidence that spatio-temporally regulated mRNA decay, outside the germline, contributes to early vertebrate development.
    Keywords:  CRISPR-Cas13d; CRISPR-Cas9; Cth1; Embryonic lethal; Gametogenesis; MZT; RNA decay; RNA-decay factor; Spatio-temporal maternal RNAs; Zebrafish
    DOI:  https://doi.org/10.64898/2026.08.20.745964
  8. bioRxiv. 2026 Oct 09. pii: 2026.10.07.757430. [Epub ahead of print]
    Organelle Volume Facilitates Spindle Positioning During C. elegans Female Meiosis.
    Denisa G Lazureanu, Eric Krueger, Wei Qiu, Aspen A Kopley-Smith, Clive S Smith, Alma P Aquino, Aastha Lele, Nadiia Voloshchuk, Daniel B Cortes, Mooncheol Park, Kunihiro Uryu, Malan Silva, Eric Trautman, Michael Innerberger, Stephan Preibisch, Roman Vaxenburg, Alyssa K Stark, Christopher K E Bleck, Molly Reilly, Meng C Wang, Hari Shroff, Francis J McNally.
      Cortical positioning of oocyte meiotic spindles is required for reducing chromosome number by segregating chromosomes into polar bodies. In C. elegans, kinesin-1 transports membrane-bound organelles inward into a central ball that is hypothesized to push the meiotic spindle outward. Using focused ion beam scanning electron microscopy, we found that the percent volume occupied by membrane-bound organelles was 28% in a mature oocyte that has completed endocytosis of the yolk precursor, vitellogenin, compared to 17% in a less mature oocyte that has not yet endocytosed vitellogenin. We therefore hypothesized that blocking endocytosis of vitellogenin would reduce the size of the central ball of organelles packed inward by kinesin-1 and limit outward movement of the spindle. Depletion of vitellogenin or proteins required for endocytosis resulted in a smaller central volume of kinesin-coated organelles and defective spindle positioning. A computer simulation of a simple exclusion model faithfully recapitulated wildtype and mutant spindle position phenotypes. These results support a volume exclusion model for positioning acentriolar meiotic spindles.
    DOI:  https://doi.org/10.64898/2026.10.07.757430
  9. bioRxiv. 2026 Oct 07. pii: 2026.10.06.756462. [Epub ahead of print]
    CYB-4/CDK-1 coordinates timing of meiotic entry, chromosome morphogenesis and oocyte maturation in C. elegans.
    Amirhossein Pezeshki, Steven J M Jones, Monique Zetka.
      Meiotic chromosome segregation requires the earlier coordination of chromosome morphogenesis with cell-cycle progression. In C. elegans, the remodeling of chromosomes in preparation for the meiotic divisions and oocyte maturation is regulated by the master cell-cycle regulator c yclin- d ependent k inase 1 (CDK-1). Here, we identify CYB-4 as a meiosis-specific B-type cyclin that is required for CDK-1-dependent functions in meiotic prophase. In a genetic suppressor analysis of a mutant defective in chromosome axis assembly, we isolated a null allele that revealed a function for CYB-4 in regulating chromosome structure at two key prophase transitions. Loss of CYB-4 first delays meiotic entry and the onset of chromosome axis formation, and at pachytene exit delays chromatin condensation, bivalent remodeling, and oocyte maturation. The defects in timely CO formation and bivalent packaging that accompany these delays are ultimately resolved before prophase exit, indicating that CYB-4 is required for the scheduling of events rather than if they occur. Together, our findings provide evidence that CDK-1 activity during meiotic prophase is defined by CYB-4 and support a model in which CYB-4/CDK-1 are essential for the sharp transitions at prophase entry and pachytene exit that coordinate chromosome morphogenesis with meiotic progression.
    DOI:  https://doi.org/10.64898/2026.10.06.756462
  10. PLoS One. 2026 ;21(10): e0361215
    A premature ovarian insufficiency-associated LMD-3 point mutation impairs protein stability and causes autophagic-lysosomal dysfunction in Caenorhabditis elegans.
    Yile Zhai, Tiantian Wang, Meixi Gong, Yuhan Liang, Wenfei Li, Xin Wang, Zhe Zhang.
      Reproductive longevity decline characterizes both natural aging and premature ovarian insufficiency (POI). While our previous work established C. elegans LMD-3 as a critical regulator of reproductive capacity, the in vivo consequences of specific clinical mutations remain unclear. Here, we modeled the POI-associated human NCOA7 W804C mutation by engineering the orthologous W690C substitution into the C. elegans lmd-3 locus. We demonstrate that this single-nucleotide substitution severely compromises LMD-3 protein stability and reduces transcript levels. This mutational destabilization is associated with profound systemic autophagic-lysosomal dysfunction, which impairs macromolecular degradation and leads to widespread proteotoxic accumulation of misfolded proteins. Coincident with these organismal defects, mutant animals exhibit an early-onset collapse in reproductive capacity driven by elevated germline apoptosis. Crucially, this pathology is consistent with reduced vitamin B12 availability; mecobalamin supplementation can mitigate the lysosomal block, restoring autophagic flux, proteostasis, and fecundity. These findings elucidate how a clinical mutation drives systemic lysosomal failure and reproductive decline, suggesting vitamin B12 supplementation as a promising metabolic intervention worth further translational exploration.
    DOI:  https://doi.org/10.1371/journal.pone.0361215
This page is being maintained by Thomas Krichel. It was last updated on 2026‒11‒01 at 7:05.