bims-cebooc 2026-10-11 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–10–11
thirteen papers selected by
Gabriele Zaffagnini, Universität zu Köln

Standardizing Cell Ontology terms for cross-study integration in the female reproductive tract.
Heterogeneity in secondary follicle development buffers the lifespan of activated oocytes to optimize female fertility in mice.
The human ovary exhibits dynamic molecular remodeling in the decades post-menopause.
Decoding the immune regulation of ovarian aging: mechanisms and therapeutic strategies.
Inheritance and selection of the mitochondrial genome.
Comprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesis.
Actin-Related Causes of Aneuploidy in Human Eggs.
ZC3H14 phosphorylation is required for nuclear speckle assembly during zygotic splicing activation in mice.
Beyond the fly: fusome conservation and its implications for germ cell biology.
emb-20 encodes a farnesyl diphosphate synthase in Caenorhabditis elegans.
Monitoring fatty acid trafficking during Drosophila melanogaster oogenesis reveals a role for the triglyceride synthase DGAT1 in protecting mitochondrial integrity.
Method for modeling oviduct function and impact on embryonic development†.
Local fluidization of an active cytoplasmic gel partitions large cells.

Sci Adv. 2026 Oct 09. 12(41): eaef2358

Standardizing Cell Ontology terms for cross-study integration in the female reproductive tract.

Huan Ting Ong, Diane C Saunders, Caroline Eastwood, Aleix Puig-Barbe, Alison Kochersberger, Anna Galligos, Bailey Marshall, Benjamin K Johnson, Caroline E Kratka, Chen Jin, Daniela Betancur, Gabriela Rapozo Guimarães, Jordan H Machlin, Jose V V Isola, Katelyn M Adam, Osmaray Morales-Casanova, Svetlana Djirackor, Taylor Schissel, Valentina Lorenzi, Xifan Wang, Xingyu Shen, Bikem Soygur, Brian Aevermann, Eliza A Gaylord, Mariko H Foecke, Norbert K Tavares, Ryan M Samuel, Sophia Szady, Srinivasan Mahalingam, Subhasri Biswas, Will Liao, Bérénice A Benayoun, Hattie Chung, Wipawee Winuthayanon, Jun Z Li, Matteo A Molè, Michael Angelo, Patricia Jeudin, Ronny Drapkin, Ariella Shikanov, Diana J Laird, Francesca Duncan, Hui Shen, Jennifer L Garrison, Mariana Boroni, Michael B Stout, Roser Vento-Tormo, Sophia H L George, Yousin Suh, Jennifer L Young, Monica M Laronda.

The female reproductive tract is essential for fertility, pregnancy, and overall health, yet many of its cellular components remain poorly defined. Recent advances in single-cell and spatial transcriptomics have begun to reveal this complexity, but inconsistent naming of cell types and states has limited the ability to compare findings across studies. To address this challenge, an international group of reproductive biologists and ontology experts collaborated to harmonize annotations within Cell Ontology, focusing on the ovary, fallopian tube, and uterus. Standardized terms are proposed for major epithelial, stromal, and germ cell populations, supported by marker gene sets and anatomical linkages. This framework provides a shared reference that can be used to harmonize existing datasets and guide annotation of future studies, enabling consistent classification of oocytes, granulosa, theca, luteal, epithelial, stromal, and immune cells across tissues. By establishing a unified taxonomy, this work lays the foundation for integrating datasets, supporting cross-tissue comparisons, and advancing the understanding of reproductive biology, health, and disease.

DOI: https://doi.org/10.1126/sciadv.aef2358
Nat Aging. 2026 Oct 08.

Heterogeneity in secondary follicle development buffers the lifespan of activated oocytes to optimize female fertility in mice.

Jing Liang, Xuebing Yang, Qian Li, Lingyu Li, Ge Wang, Lu Mu, Nan Sun, Kaiying Geng, Xindi Hu, Shudong Niu, Longzhong Jia, Yibo Wang, Xueqiang Xu, Zhen Li, Fengchao Wang, Yan Zhang, Hua Zhang.

Oocyte activation and follicular development are fundamental for fertility in mammals, yet the dynamics of activated oocytes (Act-Oos) remain unclear. Here we use a Zp3-based lineage-tracing mouse model to label Act-Oos and reconstruct their developmental trajectories and folliculogenesis across the lifespan. We uncovered age-dependent heterogeneity in Act-Oo longevity: some oocytes activated in early adulthood progressed rapidly, whereas others persisted into late or even terminal reproductive stages, supporting long-term fertility. Further analyses revealed that Act-Oo lifespan is governed by secondary follicle (SF) progression, identifying SF development as a buffering mechanism that modulates female reproductive capacity. Mechanistically, transcriptional and metabolic states vary across Act-Oos, and differential FURIN expression modulates the release of oocyte-secreted factors, coordinating Act-Oo development with that of associated SFs and thereby regulating Act-Oo lifespan. Together, these findings provide a comprehensive in vivo developmental map of Act-Oo and mouse folliculogenesis, revealing dynamic control of female reproductive capacity.

DOI: https://doi.org/10.1038/s43587-026-01237-5
bioRxiv. 2026 Aug 11. pii: 2026.03.26.714635. [Epub ahead of print]

The human ovary exhibits dynamic molecular remodeling in the decades post-menopause.

Mark A Watson, Bikem Soygur, Christina D King, Pooja R Devrukhkar, Simon Melov, Elisheva D Shanes, Mary Ellen G Pavone, Francesca E Duncan, Birgit Schilling.

The human ovary is among the first organs to show age-related functional decline, resulting in menopause. Beyond this transition, the postmenopausal ovary is often regarded as quiescent and remains poorly characterized. We analyzed the proteomes of healthy, non-pathological ovaries using mass spectrometry (data-independent acquisition) from 28 postmenopausal women (50-75 years old), stratified into three age groups (50-59, 60-69, ≥70). We quantified 5,812 protein groups and observed progressive age-associated shifts, with 117 proteins significantly altered in the ≥70 vs 50-59 age comparison. Multivariate analysis demonstrated clear separation between 50-59 and ≥70-year-old age cohorts, with protein signatures shifting from RNA/gene-regulatory functions in younger ovaries to metabolic, trafficking, and innate immune/complement pathways in older ovaries. Across differential abundance, multivariate modelling, and covariate-adjusted linear modelling, we identified a convergent set of age-associated proteins that were integrated into the 26-protein B uck P ostmenopausal O vary M olecular S ignature (BuckPOMS), a consensus molecular signature capturing progressive extracellular matrix remodeling, inflammatory signaling, and loss of structural and keratin-associated proteins with age. Representative BuckPOMS proteins, including the secreted matrisome proteins WNT4 and Fibromodulin (FMOD), were validated by immunohistochemistry. Pathway enrichment further identified an increase in inflammatory and matrisome pathways, and increased abundance of damage-associated secretory factors decades following menopause. These data fundamentally shift the notion of the postmenopausal ovary as an inert organ and instead demonstrate active and continuous molecular remodeling that has potential relevance to tissue signaling and implications for women's health.

DOI: https://doi.org/10.64898/2026.03.26.714635
Hum Reprod Update. 2026 Oct 09. pii: dmag030. [Epub ahead of print]

Decoding the immune regulation of ovarian aging: mechanisms and therapeutic strategies.

Changjing Wang, Nianyu Li, Zi-Jiang Chen, Yingying Qin, Xue Jiao.

   BACKGROUND: Ovarian aging is among the earliest functional declines in humans and acts as a pacemaker of female aging. It encompasses both physiological age-related ovarian decline and pathological accelerated aging, exemplified by premature ovarian insufficiency (POI). Increasing evidence positions the immune system as both a regulator of ovarian homeostasis and a driver of ovarian dysfunction. Age-related immunosenescence and chronic low-grade inflammation (inflammaging) coordinately drive ovarian aging through bidirectional crosstalk between systemic immunity and the ovarian immune microenvironment. POI frequently coexists with autoimmune disorders, reinforcing the central role of the immune-ovarian axis in reproductive aging. Elucidating this interplay may enable targeted immunomodulatory strategies to preserve reproductive longevity and mitigate systemic consequences of ovarian decline.
OBJECTIVE AND RATIONALE: The aim was to synthesize current evidence on (i) immune regulation of normal ovarian physiology; (ii) immune alterations in physiological ovarian aging, including systemic immunosenescence and ovarian immune microenvironment remodelling; (iii) autoimmune dysregulation in POI; and (iv) the translational potential of immunomodulatory interventions for mitigating ovarian aging.
SEARCH METHODS: Original articles published up to April 2026 were identified through PubMed using combinations of the terms 'immune system', 'ovarian function', 'inflammation', 'immune cell', 'ovarian aging', 'menopause', 'primary ovarian insufficiency', and 'therapeutics'.
OUTCOMES: Immune cells and cytokine networks form a specialized regulatory axis that governs folliculogenesis, ovulation, and luteal dynamics. This review synthesizes emerging evidence showing that this immune-ovary axis undergoes profound remodelling during reproductive aging and that immune dysregulation is a causal driver of ovarian functional decline. Systemically, the menopausal transition accelerates immunosenescence and amplifies pro-inflammatory cytokine production. Locally, the aging ovary exhibits chronic inflammation, NLRP3 inflammasome activation, and accumulation of senescent cells with a senescence‑associated secretory phenotype. These changes coincide with a shift from tissue‑resident to monocyte‑derived macrophages and expansion of inflammatory γδ and double‑negative T cells. This progressive loss of immune homeostasis promotes follicular depletion, stromal fibrosis, and impaired steroidogenesis. POI represents a pathological extreme of this axis, characterized by autoimmune comorbidities, B cell-driven humoural abnormalities, T cell dysregulation, and genetic variants affecting immune pathways. Comparative analysis reveals both conserved inflammatory signatures shared with physiological aging and POI-specific immune features that reflect overt immune-mediated ovarian injury. By integrating systemic, local, and disease-specific immune mechanisms, this review reframes ovarian aging as a modifiable immunological process. Therapeutically, emerging immunomodulatory strategies range from molecular agents targeting inflammatory mediators and senescence programs, through cell-based immune reprogramming with stem cells, regulatory T cells, and senolytic immune effectors, to lifestyle-driven systemic immunomodulation. These strategies show promise in restoring ovarian immune homeostasis and extending the reproductive lifespan, with several of these approaches now advancing toward early-phase clinical evaluation.
WIDER IMPLICATIONS: Collectively, the current evidence positions immune dysregulation as a mechanistic driver, rather than a secondary correlate, of ovarian aging. Integrating immune biomarkers into predictive frameworks and designing stratified immunomodulatory trials may shift ovarian aging management from symptomatic hormone replacement toward mechanism-based intervention. Reframing ovarian aging as a modifiable immune-mediated process offers new opportunities to extend female reproductive longevity and the female health span.
REGISTRATION NUMBER: N/A.

Keywords:  immune cell; immune system; inflammation; menopause; ovarian aging; ovarian function; premature ovarian insufficiency; therapeutics

DOI:  https://doi.org/10.1093/humupd/dmag030
Nat Rev Genet. 2026 Oct 05.

Inheritance and selection of the mitochondrial genome.

Qin Xie, Harry E Walker, Michal Minczuk, Marcos R Chiaratti, Patrick F Chinnery.

The functioning mitochondrial genome is essential for cellular energy production. Being strictly maternally inherited and possessing limited DNA repair capacity, mitochondrial DNA (mtDNA) replication errors tend to accumulate over time. If left unchecked, these errors can accumulate through the female germline over successive generations, potentially leading to species extinction. However, this outcome is not observed in most species, including humans, which implies the existence of mechanisms that counteract the progressive accumulation of deleterious mtDNA mutations. Recent technological advances are building a deeper understanding of the processes that preserve mtDNA integrity, including the molecular and cellular basis and timing of purifying selection. This new knowledge helps to explain how mtDNA can change rapidly over just a few generations, whilst remaining compatible with the independently inherited, evolving nuclear genome.

DOI: https://doi.org/10.1038/s41576-026-01019-0
Cell. 2026 Oct 08. pii: S0092-8674(26)01196-7. [Epub ahead of print]

Comprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesis.

William N Colgan, Luke W Koblan, JoAnne Villagrana, Tien-Chi Jason Hou, Minming Wang, Gokul Gowri, Whitney Chandler, Leonardo A Sepúlveda, Didar Ciftci, Karina Smolyar, Kathryn E Yost, Alicia Young, Lars Wittler, Styliani Markoulaki, Kyle M Loh, Xiaowei Zhuang, Nir Yosef, Zachary D Smith, Jonathan S Weissman.

  A comprehensive cell fate map of mammalian embryogenesis has remained out of reach given the scale, cellular diversity, and non-deterministic nature of development in utero. Here, we use PEtracer to continuously install heritable genetic marks as development progresses, reconstructing lineage trees that resolve ∼75% of cell divisions across >1.4 million cells from 16 replicate embryos. We pair these trees with deep transcriptional profiling to resolve cell fate biases, restriction timing, progenitor pool sizes, and lineage relationships throughout embryogenesis. Using this quantitative reference, we uncover strikingly reproducible lineage architecture between replicate embryos and chart the lineage dynamics driving fate specification across diverse tissues. Specific biological insights include the progressive restriction of neural crest fate, the relative contributions of distinct mesodermal origins to endothelium, and the dynamics of axial elongation. This work provides a foundation for a quantitative and predictive understanding of mammalian development.

Keywords:  PEtracer; cell fate specification; lineage tracing; mouse embryogenesis; scRNA-seq; single-cell RNA sequencing

DOI:  https://doi.org/10.1016/j.cell.2026.09.050
FASEB J. 2026 Oct 15. 40(19): e72366

Actin-Related Causes of Aneuploidy in Human Eggs.

Yi Zheng, Wenhan Ma, Xinmiao Hu, Danyang Li, Ming Zhang, Hui Luo.

  Gametogenesis (oogenesis and spermatogenesis) relies on a specialized form of cell division known as meiosis. During this process, chromosomes in parental cells undergo two successive rounds of segregation, resulting in a halving of their number and the formation of haploid germ cells, which is essential for subsequent fertilization. However, in human female gametogenesis, errors in chromosome segregation occur at a notably high frequency, leading to the formation of oocytes with abnormal chromosome numbers. Once fertilized, such oocytes often develop into aneuploid embryos, which exhibit severely impaired developmental potential and frequently end in implantation failure or early pregnancy loss. Notably, with advancing maternal age, the frequency of errors in meiotic maturation mediated by the actin and microtubule cytoskeletons increases significantly, thereby elevating the overall risks of infertility, pregnancy termination, and birth defects such as Down syndrome. This article aims to systematically review recent advances in the mechanisms by which actin contributes to the formation of aneuploidy in female meiosis, with a particular focus on findings from human oocytes.

Keywords:  aging; aneuploidy; chromosome segregation; human fertility; meiosis; oocyte

DOI:  https://doi.org/10.1096/fj.202504914RR
EMBO Rep. 2026 Oct 07.

ZC3H14 phosphorylation is required for nuclear speckle assembly during zygotic splicing activation in mice.

Yang Wang, Hua Zhang, Zhe-Wei Hu, Dan Su, Jing Zhao, Xiao-Ying Fan, Li-Ling Liu, Heng-Yu Fan.

Following zygotic genome activation (ZGA) in embryos, nuclear speckles, which are subnuclear domains where pre-mRNA undergoes splicing, are reassembled in a process called zygotic splicing activation (ZSA). ZSA is vital for early development, but its regulation is poorly understood. This study identifies the RNA-binding protein ZC3H14 as a key promoter of nuclear speckle formation during ZSA. Although viable, Zc3h14 knockout mice exhibit reduced female fertility. Most embryos from these females arrest during the 1-cell to 2-cell transition, and the remaining embryos arrest at the 2-cell stage, highlighting a critical role for maternally deposited ZC3H14. The protein localizes to nuclear speckles, and its phosphorylation by CDK12/13 regulates mRNA binding and initial speckles assembly. Blocking this phosphorylation disrupts proper splicing and leads to abnormal RNA accumulation. Consequently, phosphorylation-mimicking or phosphorylation-blocking ZC3H14 mutants expressed in zygotes positively and negatively affect development, respectively. Taken together, our results indicate that ZC3H14 phosphorylation by CDK12/13 maintains fertility in female mice by promoting nuclear speckle formation during ZSA.

DOI: https://doi.org/10.1038/s44319-026-00950-x
Curr Opin Cell Biol. 2026 Oct 06. pii: S0955-0674(26)00082-7. [Epub ahead of print]103 102694

Beyond the fly: fusome conservation and its implications for germ cell biology.

Amanda M Powell, Elizabeth T Ables.

The survival of sexually reproducing species depends on the production of competent germ cells. Before meiotic entry, the expansion of specialized totipotent cells is essential for establishing a sufficient germ cell pool during gametogenesis. Growing evidence suggests that the mechanisms guiding the earliest stages of germ cell development are evolutionarily conserved across invertebrate and vertebrate species. A defining feature of germ cell maturation is the formation of germline cysts, interconnected groups of germ cells that undergo mitotic divisions to expand the gamete progenitor pool. A second characteristic now emerging is the formation of a specialized, yet still enigmatic organelle known as the fusome. First characterized in insects and more recently identified in vertebrates, the fusome represents an underexplored component of germline development. Here, we review recent advances in fusome biology with particular focus on insights from female Drosophila, where its structure and function have been most extensively characterized.

DOI: https://doi.org/10.1016/j.ceb.2026.102694
Genetics. 2026 Oct 08. pii: iyag277. [Epub ahead of print]

emb-20 encodes a farnesyl diphosphate synthase in Caenorhabditis elegans.

Ryosuke Konuma, Ikuko Maejima, Ichiro Kawasaki, Takuya Norizuki, Kenta Sugiura, Miyuki Sato, Ken Sato.

  Oocytes grow through biosynthesis of cellular components as well as endocytosis to take up nutrients from the extracellular space. They also develop cortical granules that are exocytosed after fertilization to alter the extracellular environment. We have previously shown that defects in cortical granule formation and exocytosis cause an osmotically sensitive embryo phenotype and embryonic lethality. To identify regulators of cortical granule formation and exocytosis, we characterized a Caenorhabditis elegans emb-20(g27) mutant displaying similar phenotypes at a restrictive temperature (25 °C). The fluorescently labeled cortical granule marker, GFP::CAV-1, mainly localized to cortical granules and the plasma membrane in control oocytes at 15 °C and 25 °C and in emb-20(g27) oocytes at 15 °C. In contrast, GFP::CAV-1 largely accumulated in fine punctate structures in emb-20(g27) mutant oocytes at 25 °C. The emb-20(g27) mutants also exhibited impaired endocytic yolk uptake by oocytes. We revealed that the emb-20(g27) mutant harbors a missense mutation in the fdps-1 gene, which encodes a farnesyl diphosphate synthase in the mevalonate pathway, causing a Glu282-to-Lys substitution. Farnesyl diphosphate is an essential precursor for generating geranylgeranyl groups for the prenylation of RAB small GTPases. We found that the endoplasmic reticulum-to-Golgi transport regulator, RAB-1, and endocytic regulators, such as RAB-5, RAB-7, and RAB-11, lost their organelle localization and became diffusely distributed throughout the cytoplasm and nucleus in emb-20(g27) mutant oocytes at 25 °C, and their prenylation states were drastically affected. These results suggest that EMB-20/FDPS-1 is essential for maintaining appropriate RAB GTPase function to preserve active membrane trafficking in developing oocytes.

Keywords:   C. elegans ; Farnesyl diphosphate synthase; WormBase; fertilization; oogenesis; prenylation; small GTPase

DOI:  https://doi.org/10.1093/genetics/iyag277
bioRxiv. 2026 Aug 12. pii: 2026.08.10.743872. [Epub ahead of print]

Monitoring fatty acid trafficking during Drosophila melanogaster oogenesis reveals a role for the triglyceride synthase DGAT1 in protecting mitochondrial integrity.

Roger P White, Marcus D Kilwein, Michael A Welte.

Successful oogenesis requires the precise coordination of nutrient uptake, storage, and utilization to meet the high metabolic demands of egg production. In mammals, fatty acid (FA) metabolism has emerged as a key driver of oocyte maturation; however, the mechanisms by which follicles regulate FA trafficking and utilization remain poorly understood across all systems. To address these issues, we leverage the genetic tractability of Drosophila melanogaster oogenesis. We found that nurse cell mitochondria are metabolically active and catabolize FA in a stage-dependent manner, with fatty acid oxidation (FAO) peaking during mid-oogenesis. By exposing explanted follicles to fluorescently labeled FAs, we monitored FA trafficking and found massive enrichment in lipid droplets. Mutants for the triglyceride lipase ATGL exhibited a reduction in both mitochondrial membrane potential and FAO, suggesting that mitochondria utilize FA from triglycerides stored in LDs. To determine the significance of this transient FA storage in LDs, we prevented the formation of nurse cell LDs with mutations in the triglyceride synthase DGAT1. The DGAT1 mutant follicles display excess accumulation of FAs in mitochondria, mitochondrial stress, and developmental arrest. We find that this mitochondrial dysfunction and follicle arrest are consequences of FA toxicity to mitochondria: limiting FA influx into follicles or FA import into mitochondria alleviates these defects. Our findings demonstrate that LD-derived FAs are actively mobilized to fuel the energy demands of oogenesis while LDs buffer against lipotoxicity, revealing a critical balance between FA storage and oxidation. These findings highlight LDs as central hubs regulating energy homeostasis and developmental progression in the follicle.
Author Summary: Oogenesis places extraordinary metabolic demands on the follicle, yet the energy source for follicle development is not well understood. In fruit flies, follicles take in large amounts of lipids from the hemolymph, the insect blood, and accumulate massive fat stores in the form of lipid droplets. Whether these stores are reserved for the embryo or already power oogenesis was unclear. Using mutants and fluorescent probes for metabolic activity, we found that some fatty acids are released from the lipid droplets and power energy production in mitochondria; this energy source is important for successful oogenesis. We then fed flies fluorescently labeled fatty acids and determined how these fatty acids travel when lipid droplet formation can occur versus when it is abolished. In the former case, fatty acids accumulate in lipid droplets; in the latter, they flood into mitochondria, causing mitochondrial dysfunction, reduced ATP levels, and follicle death. We can correct all these defects by limiting lipid influx specifically into mitochondria. Our findings reveal an important role for lipid droplets during oogenesis. They act as a metabolic buffer, supplying sufficient amounts of fatty acids to mitochondria for energy production while shielding the mitochondria from toxic lipid levels.

DOI: https://doi.org/10.64898/2026.08.10.743872
Biol Reprod. 2026 Oct 09. pii: ioag225. [Epub ahead of print]

Method for modeling oviduct function and impact on embryonic development†.

Kalli K Stephens, Vakil Ahmad, Maria A Silva, Makenna K Shifflett, Jiude Mao, Jason A Rizo, Mark I Hunter, Andrew M Kelleher, Wipawee Winuthayanon.

Direct experimental analysis of the mammalian oviduct is constrained by limited tissue access and the short lifespan of ex vivo preparations. Extracellular matrix-embedded three-dimensional epithelial organoids provide longer-term in vitro models. However, their inward-facing apical surface and the absence of supporting stromal cells limit physiological studies of the oviduct, including ciliary activity and maternal-embryonic interactions. Here, we provide a step-wise protocol detailing the generation of mouse and human oviductal assembloids in which epithelial cells form an outward-facing (apical-out) layer around a stromal core. Epithelial and stromal cells from adult mouse oviducts or human Fallopian tubes are isolated, expanded separately, and subsequently aggregated in a rotational culture system. The protocol also outlines morphological and immunostaining criteria for confirming cellular organization, whole-mount detection of external cilia, measurement of ciliary beat frequency, and co-culture of mouse assembloids with preimplantation embryos. Mouse and human assembloids retained epithelial and stromal identity and displayed cilia at the accessible outer surface. In a proof-of-concept experiment, embryos co-cultured with the assembloids developed to blastocysts at a rate similar to that of in vivo-derived blastocysts. This reductionist system provides a straightforward and tractable model to investigate oviduct physiology and embryo-maternal communication while allowing direct manipulation and observation of the epithelial interface.

DOI: https://doi.org/10.1093/biolre/ioag225
bioRxiv. 2026 Aug 12. pii: 2026.08.11.744254. [Epub ahead of print]

Local fluidization of an active cytoplasmic gel partitions large cells.

Luolan Bai, Christine M Field, Ai Kiyomitsu, Yunyi Shen, Natalia D Orlovsky, Tomomi Kiyomitsu, Timothy J Mitchison.

Early animal embryos undergo rapid cleavages that partition cytoplasmic volumes orders of magnitude larger than those of somatic cells 1 . Each division must reposition nuclei and centrosomes and distribute organelles within minutes, over distances up to hundreds of micrometers 2 . Cleavage furrows are positioned by microtubule asters 3,4 , but the mechanical mechanism for long-range transport of cytoplasmic components before cytokinesis was unknown. Here, we show that cytoplasm behaves as a locally switchable active material. Fluidization at the midplane allows bulk actomyosin to convert a local mechanical asymmetry into directed global flows of all components as a composite material. Using an actin-intact cycling Xenopus egg extract together with Xenopus and medaka embryos, we find that F-actin mechanically couples microtubule asters, organelles, nuclei and centrosomes into a gel-like composite that propagates forces over hundreds of micrometers. After mitosis, Aurora B kinase patterns a locally fluidized midplane, from which myosin-II contractility drives coherent cytoplasmic flows. A fluid dynamics model accounts for the observed flow geometry and rates. Our results reveal how local control of the material state of cytoplasm converts mitotic symmetry breaking into long-range intracellular transport and identify bulk actomyosin as the active stress generator that partitions embryonic cytoplasm as a composite gel.

DOI: https://doi.org/10.64898/2026.08.11.744254