bims-cebooc 2026-10-18 papers

bims-cebooc

Biomed News

on Cell biology of oocytes

Issue of 2026–10–18
twelve papers selected by
Gabriele Zaffagnini, Universität zu Köln

Declining ribosome function limits oocyte longevity.
Age-dependent dysregulated post-ovulatory debris clearance promotes ovarian fibroinflammation.
Exogenous pressure during in vitro follicle growth suppresses oocyte size expansion without impairing functional competence.
The Human Ovary Exhibits Dynamic Molecular Remodeling in the Decades Post-Menopause.
The CCT chaperonin is a context-dependent regulator of RNA-binding protein phase transitions.
Mitotic and meiotic midbody remnants: Divergent architectures with distinct clinical applications.
Dynamics of bicoid mRNA localisation and translation dictate morphogen gradient formation.
Attribute Network-based Ranking (ANeR) identifies conserved translational fingerprints of M-phase.
Modelling mouse embryogenesis from chemically induced totipotent stem cells.
Multi-omic profiling reveals impaired luteal resolution and CHK2-regulated inflammation in ovarian aging.
Proteome-wide quantification of protein turnover in frog and fly embryos reveals divergent strategies of maternal inheritance.
Parental genome reprogramming drives allelic convergence while preserving parent-of-origin memory during human early embryonic development.

bioRxiv. 2026 Sep 30. pii: 2026.09.29.755503. [Epub ahead of print]

Declining ribosome function limits oocyte longevity.

Kayla Judson, Katie J Danielson, Shuang Tang, Sahil Chandhok, Elizabeth Hui, Fiona Wong, Thibault Mayor, Karen Schindler, Ethan J Greenblatt.

  Protein synthesis declines with age across many tissues, but whether this decline actively contributes to physiological aging remains unclear. Oocytes may be particularly vulnerable because they rely on ribosomes synthesized during growth and maintained for prolonged periods without continual replacement. Here we show that declining translational capacity is a causal component of oocyte aging. An unbiased genetic screen identified ribosome dosage as a major determinant of oocyte longevity, and experimentally reducing ribosome abundance was sufficient to accelerate the loss of developmental competence and prematurely recapitulate meiotic defects that arise during natural aging, while also producing defects in early embryonic development. Ribosomes isolated from aged Drosophila oocytes exhibit ~50% lower translational activity despite only a modest reduction in ribosome abundance and preserved gross structure and composition, with both ribosomal subunits contributing to this functional decline. Protein synthesis also declines markedly in aged metaphase-I mouse oocytes. Together, these findings identify long-lived translational machinery as an intrinsic vulnerability of the oocyte and establish declining ribosome function as a mechanistic contributor to reproductive aging.

Keywords:  Fertility; aging; meiotic spindle; oocyte; ribosome; translation

DOI:  https://doi.org/10.64898/2026.09.29.755503
bioRxiv. 2026 Sep 29. pii: 2026.09.23.753904. [Epub ahead of print]

Age-dependent dysregulated post-ovulatory debris clearance promotes ovarian fibroinflammation.

Aubrey Converse, Madeline J Perry, Shweta S Dipali, Prianka H Hashim, Jennifer L Gerton, Michele T Pritchard, Francesca E Duncan.

The ovary is one of the first organs to age, with declines in oocyte quantity and quality leading to infertility and loss of endocrine function. Why the ovary ages earlier than somatic tissues has remained enigmatic but may relate to its highly dynamic physiology and substantial demand for cellular debris clearance. Each ovulation forms a corpus luteum (CL), a transient endocrine structure which supports pregnancy but regresses in its absence. Because CLs have a short functional lifespan but prolonged structural regression, they represent a substantial source of ovarian debris. We hypothesized that post-ovulatory debris clearance becomes impaired with age and contributes to ovarian fibroinflammation. Using a CL-labeling system, we demonstrated that CLs from reproductively old mice show dysregulated regression, resulting in an accumulation of persistent CLs (pCLs) which appeared concurrently with ovarian multinucleated giant cells (MNGCs). Laser capture microdissection, RNA sequencing, and histological evaluation of CLs, pCLs, and MNGCs demonstrated that pCLs were focal hotspots of proinflammatory and debris-associated signatures enriched in lipids, extracellular matrix, and immune cells. Although pCLs retained luteal features, they were transcriptionally more similar to MNGCs than CLs. Consistent with this, an ex vivo CL model acquired MNGC-associated molecular features during extended culture, suggesting that pCLs may represent sites of MNGC formation. Culture of isolated follicles or ovarian stromal organoids with factors from MNGC-enriched explants induced compartment-specific fibroinflammatory responses. These findings provide novel mechanistic insight into ovarian aging, whereby post-ovulatory debris clearance is compromised with age, leading to pCL accumulation, MNGC formation, and a fibroinflammatory milieu.

DOI: https://doi.org/10.64898/2026.09.23.753904
Biol Reprod. 2026 Oct 15. pii: ioag226. [Epub ahead of print]

Exogenous pressure during in vitro follicle growth suppresses oocyte size expansion without impairing functional competence.

Tomohiro Kohama, Go Nagamatsu.

  Pressure stimuli, such as those arising from physical forces and hydrostatic pressure in vivo, are known to regulate cellular differentiation and growth. In the ovarian microenvironment, such cues are important regulators of folliculogenesis; however, their roles during in vitro follicle growth remain unclear. This study examined the effects of exogenous pressure on mouse preantral follicles cultured in a gas-pressurized system. Follicles were cultured under 0, 33, or 100 kPa for 8 days. Although exogenous pressure suppressed oocyte diameter expansion (0 kPa, 79.9 μm; 33 kPa, 74.7 μm; 100 kPa, 69.0 μm), the number of transzonal projection and the expression of Myo10 were comparable among groups, indicating that granulosa cell-oocyte communication was maintained. Following in vitro maturation and fertilization, oocytes from the 33 and 100 kPa groups showed comparable rates of maturation, fertilization, and blastocyst development to those of the 0 kPa group. Live offspring were successfully obtained in all groups. Further, the total RNA and expression levels of representative maternal transcripts in oocytes were comparable among groups. Additional analysis revealed that oocytes of similar diameters obtained after shorter culture periods under non-pressurized conditions showed significantly lower RNA content and developmental competence than those grown under exogenous pressure. These results indicate that oocyte diameter does not necessarily reflect cytoplasmic maturation and functional competence under exogenous pressurized conditions. Overall, our findings highlight the limitations of using oocyte diameter as an oocyte quality indicator and provide new insights into the role of pressure stimuli in folliculogenesis and in vitro follicle growth systems.

Keywords:   in vitro follicle growth (IVG); cytoplasmic maturation; exogenous pressure; oocyte diameter

DOI:  https://doi.org/10.1093/biolre/ioag226
Aging Cell. 2026 Oct;25(10): e70714

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 5812 protein groups and observed progressive age-associated shifts, with 117 proteins significantly altered in the ≥ 70 versus 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 modeling, and covariate-adjusted linear modeling, we identified a convergent set of age-associated proteins that were integrated into the 26-protein Buck Postmenopausal Ovary Molecular Signature (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.

Keywords:  aging; extracellular matrix; inflammation; postmenopausal ovary; proteomics; reproductive aging; senescence

DOI:  https://doi.org/10.1111/acel.70714
MicroPubl Biol. 2026 ;2026

The CCT chaperonin is a context-dependent regulator of RNA-binding protein phase transitions.

Mingze Gao, Corrin C Hays, Jennifer A Schisa.

RNA-binding proteins (RBPs) undergo regulated phase transitions during oogenesis that are critical for maternal mRNA regulation. In C. elegans , the CCT chaperonin prevents ectopic condensation of RBPs in maturing oocytes, including MEX-3 and CAR-1 . Here, we show that CCT differentially affects oocyte RBP condensation depending on protein identity and cellular context. Depletion of CCT did not cause ectopic condensation of the P-granule proteins GLH-1 and PGL-1 . During heat stress, CCT depletion reduced MEX-3 and CAR-1 condensation, opposite from the phenotype in normally maturing oocytes. These findings reveal CCT as a context-dependent regulator of RBP phase transitions in oocytes.

DOI: https://doi.org/10.17912/micropub.biology.002420
Cell Genom. 2026 Oct 14. pii: S2666-979X(26)00248-X. [Epub ahead of print]6(10): 101386

Mitotic and meiotic midbody remnants: Divergent architectures with distinct clinical applications.

Karen Schindler, Ahna R Skop.

  Midbody remnants (MBRs), once considered inert cytokinetic debris, are now recognized as architecturally specialized, translationally active organelles whose functions reflect the mode of cell division. This review compares MBR biology in symmetric somatic mitosis and asymmetric oocyte meiosis. In somatic cells, MBRs can be retained or secreted as large extracellular vesicles that carry midbody proteins, RNAs, and translation machinery; their enrichment in stem and cancer cells implicates them in cell-state regulation and identifies them as promising, though unvalidated, substrates for liquid-biopsy biomarkers and therapeutic targeting. In oocytes, meiotic midbodies form a distinctive ring-cap architecture that concentrates local translation and restricts maternal products to the egg, thereby supporting developmental competence. Together, these studies establish division mode as a key determinant of midbody architecture, cargo, fate, and translational potential, linking cytokinesis to cancer biology and reproductive medicine.

Keywords:  ARC; EVs; MB; MBR; cancer biomarkers; developmental competence; division mode specialization; extracellular vesicles; liquid biopsy; localized translation; mMB; mMBR; meiotic midbody; meiotic midbody remnant; midbody; midbody remnant; oocyte quality

DOI:  https://doi.org/10.1016/j.xgen.2026.101386
EMBO J. 2026 Oct 10.

Dynamics of bicoid mRNA localisation and translation dictate morphogen gradient formation.

Thamarailingam Athilingam, Elise L Wilby, Pierre Bensidoun, Antonio Trullo, Morgane Verbrugghe, Jérémy Dufourt, Xingzhu Shi, Mounia Lagha, Timothy E Saunders, Timothy T Weil.

The transcription factor Bicoid (Bcd) protein guides early Drosophila patterning and is the best-characterised morphogen. The source of the morphogen, bcd mRNA, is maternally deposited during oogenesis and localised to the anterior pole. When and where Bcd protein is produced and how this protein gradient is dynamically shaped remains contentious. Here, we use the SunTag reporter system to quantitatively examine the spatiotemporal profile of bcd mRNA translation in vivo. We show that association with Processing bodies (P bodies) in mature oocytes prevent premature bcd mRNA translation. Following egg activation, bcd mRNA dissociates from P bodies and translation is observed at the anterior pole. Translation remains largely restricted to the anterior domain throughout early development. At cellularisation, translation ceases and the remaining bcd mRNA associates with reformed P bodies, which appear to block any further translation. We use these observations to create a new modified synthesis-diffusion-degradation model of Bcd gradient, which is consistent with experimental measurements. Overall, our study reveals that bcd mRNA translation is tightly controlled in space and time during oogenesis and early embryogenesis.

DOI: https://doi.org/10.1038/s44318-026-00927-5
Nucleic Acids Res. 2026 Oct 13. pii: gkag970. [Epub ahead of print]54(19):

Attribute Network-based Ranking (ANeR) identifies conserved translational fingerprints of M-phase.

Sarah B Eivers, Axelle Baumgartner, Marcio Dorn, Catherine Jessus, Juliana Silva-Bernardes, Enrico Maria Daldello.

Entry into M-phase requires mRNA translation, but whether mitotic and meiotic divisions share a conserved translational programme and which newly synthesized proteins promote Cdk1 activation remain unclear. We developed Attribute Network-based Ranking (ANeR), a multi-objective network-based method that ranks mRNAs according to their proximity to a training group across heterogeneous two-condition omics datasets. Applied to 30 datasets covering mitotic and meiotic divisions, ANeR identified a conserved M-phase translational fingerprint. Benchmarking ANeR predictions against independent mitotic datasets, together with experimental validation in Xenopus oocytes, confirmed that ANeR prioritizes proteins whose accumulation increases during both mitotic and meiotic M-phases. Application of ANeR to the meiotic translational programme identified Fam76b and Cdca3 as previously unrecognized translationally activated regulators required for timely Cdk1 activation, demonstrating that ANeR can uncover new regulators of meiotic M-phase. Analysis of the oocyte translational programme established how broadly CPE/PAS regulatory rules apply, identified transcripts that do not conform to these rules, and experimentally validated their translational activation. Together, these findings establish that vertebrate mitotic and meiotic transitions share a conserved programme of translationally regulated transcripts and demonstrate that ANeR can identify new regulators of cell division. Broadly, ANeR provides a flexible framework for investigating diverse biological questions using a collection of two-condition datasets.

DOI: https://doi.org/10.1093/nar/gkag970
Nature. 2026 Oct 14.

Modelling mouse embryogenesis from chemically induced totipotent stem cells.

Hua Wu, Yanyan Hu, Hanzhi Yu, Nana Huang, Lu Shi, Menghan Gao, Xinghan Du, Xue Lu, Yuxia Zhang, Xiya Sun, Xiaoqing Xu, Zhimin Liu, Junsong Yuan, Wei Zhou, Qiliang Shao, Dan Wang, Yangyu Zhao, Tianhua Ma, Sheng Ding.

The ability to faithfully initiate embryogenesis from a single, induced non-germline cell type, akin to the totipotent blastomeres, remains a considerable challenge in developmental and synthetic biology1-14. Here we established conditions that enable the continuous ex utero development of mouse embryo models (EMs), starting solely from the chemically induced totipotent-like stem cells (ciTotiSCs)15 and spanning the pre-implantation morula, blastocysts and post-gastrulation stages with both embryonic and extraembryonic compartments. These ciTotiSCs self-organized into blastocyst-like structures that closely resembled natural blastocysts in both morphology and lineage segregation. The resulting ciTotiSC-derived EMs (ciToti-EMs) successfully progressed through key developmental milestones, including gastrulation, embryonic axis formation, haematopoiesis and early organogenesis, closely resembling embryonic day 8.5 (E8.5) natural embryos (NEs). Furthermore, extended culture led to the development of functional cardiac tissues in ciToti-EMs, highly comparable to those of E10.5 NEs. These findings demonstrate an extraordinary ability of a single induced cell type, ciTotiSCs, to autonomously recapitulate the complete spectrum of early mouse embryogenesis. Our ciToti-EM system provides a powerful model for investigating mammalian embryonic development and opens new avenues for creating multicellular organisms from non-germline cells.

DOI: https://doi.org/10.1038/s41586-026-11164-5
bioRxiv. 2026 Oct 01. pii: 2026.09.30.755521. [Epub ahead of print]

Multi-omic profiling reveals impaired luteal resolution and CHK2-regulated inflammation in ovarian aging.

Liubin Yang, Zhongwei Sun, Xinlong Luo, Carolina Leynes, Isabelle Lorenzo, Ashley Pawelka, Meaghan Donahue, Mancy Tong, Hugh S Taylor, Yong-Hui Jiang, Brendan Lee, Tao P Wu, Jason D Heaney.

The ovary ages earlier than most other organs, but the molecular mechanisms that drive this decline remain unclear. To gain more insight into this process, we profiled ovaries from young and reproductively aged mice after synchronized ovulation and found that aging was marked by the accumulation of luteal cells with increased steroidogenic, antigen presentation and inflammatory gene expression. DNA methylation was globally preserved in aged ovaries but showed focal age-associated changes at gene regulatory regions. Protein profiling identified an increase in checkpoint kinase 2 (CHK2), a DNA damage response protein encoded by the CHEK2 gene associated with the timing of natural menopause in humans. CHK2 and DNA damage markers were increased in aged mice and human ovarian somatic cells. Transient CHK2 inhibition in aged mice increased the proportion of mature oocytes and blastocyst formation and reversed inflammatory signatures in granulosa cells. These findings identify defective luteal resolution and inflammation as features of ovarian aging and suggest that CHK2 induces a reversible age-associated inflammatory signature. Our results show that reproductive decline may remain pharmacologically modifiable during ovarian aging via regulation of the inflammatory response.

DOI: https://doi.org/10.64898/2026.09.30.755521
bioRxiv. 2026 Sep 29. pii: 2026.09.28.754234. [Epub ahead of print]

Proteome-wide quantification of protein turnover in frog and fly embryos reveals divergent strategies of maternal inheritance.

Edward R Cruz, Argit Marishta, Gloria Bao, Alexander N T Johnson, Felix C Keber, Vyas Pujari, Daniil Ivanov, Michael Neinast, Marc W Kirschner, Joshua D Rabinowitz, Eric F Wieschaus, Martin Wuhr.

Every embryo inherits a maternal proteome that it must remodel with zygotic proteins to build its many cell types. The fate of the maternal proteome remains contested because indirect measurements cannot resolve it. Here, we combine 18O-water labeling with multiplexed proteomics to quantify protein turnover proteome-wide in frog and fly embryos. Through hatching, the frog preserves the bulk of its maternal proteome, confining rapid degradation to a small regulatory module. The fly cannot meet its synthesis demand from yolk alone and instead degrades nearly all maternal proteins, including housekeeping proteins long assumed stable, recycling them into new protein. Yet the turnover hierarchy is conserved, with disordered and regulatory proteins degrading fastest, while the fly rescales the whole proteome ~eightfold faster. These results recast the developmental proteome as both informational inheritance and metabolic reserve, establish 18O-water labeling as a turnover method for non-feeding organisms, and provide a resource of embryonic half-lives.

DOI: https://doi.org/10.64898/2026.09.28.754234
Genome Res. 2026 Oct 13.

Parental genome reprogramming drives allelic convergence while preserving parent-of-origin memory during human early embryonic development.

Fanqing Xu, Qian Liu, Zhengrong Du, Yuwen Xiu, Qianying Guo, Jie Qiao, Peng Yuan, Liying Yan.

Human sperm and oocytes carry highly distinct DNA methylation landscapes, yet parental DNA methylation ultimately converges to a largely equivalent state, raising the question of when and how the allelic DNA methylome is reprogrammed toward convergence. Here, we present an integrated allelic analysis of DNA methylation and transcriptome dynamics throughout human pre- to peri-implantation development, a stage that lays the foundation for future development. We find that oocyte-specific hypermethylated regions retain maternal-biased DNA methylation asymmetry throughout early development, whereas paternal hypermethylation at sperm-specific regions is erased after fertilization and re-established during peri-implantation. Whole-genome parental DNA methylation levels converge across all lineages at embryonic days 8 to 12, prior to gastrulation, although the timing of this equilibrium differs among genomic elements. Notably, a subset of transposable elements, including SVAs and LTR12 elements, remains persistently maternally hypermethylated. Finally, we identify parent-of-origin-biased genes involved in early human embryonic development and find that these genes are enriched for dosage-sensitive genes. We further show that epiblast-specific parental expression bias is associated with genes implicated in neurodevelopmental disorders. These findings highlight the developmental and clinical relevance of allele-specific DNA methylation and transcription regulation during the earliest stages of human development.

DOI: https://doi.org/10.1101/gr.281969.126