bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–10–25
thirteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Declining centromere strength compromises meiotic chromosome segregation in aging oocytes.
  2. Single-cell TimeLapse-seq reveals MTA is an essential retrotransposon orchestrating mouse zygotic genome activation.
  3. Single-oocyte proteome-transcriptome co-profiling reveals a role of dysregulated lactate metabolism in oocyte aging.
  4. No Female Germline Stem Cells Were Identified by Advanced Dual Recombinase-Based Lineage Tracing System.
  5. Stella safeguards proteostasis via regulating UBE2D3 translation in the maternal-to-zygotic transition.
  6. Msps/XMAP215 Is Essential for Oocyte Specification in the Drosophila Ovary.
  7. Reduced insulin/IGF-1 signaling extends reproductive span through somatic gonadal collagen-mediated maintenance of oocyte and embryo quality in Caenorhabditis elegans.
  8. Establishing Polycomb regulatory landscapes in human early development.
  9. Insights into Cytoplasmic Maturation in Human Oocytes: Organelle Dynamics, Ionic Homeostasis, and Translational Regulation.
  10. Multiplexed embryo profiling links cellular state to zygotic genome activation in single cells.
  11. RanGAP1 coordinates the ER-lamina interface to drive de novo nuclear envelope reassembly in mouse embryos.
  12. DMRT1 is required at two steps of ovarian differentiation in rabbits.
  13. The postpartum recovery window as a determinant of maternal aging.
  1. J Cell Biol. 2026 Nov 02. pii: e202606132. [Epub ahead of print]225(11):
    Declining centromere strength compromises meiotic chromosome segregation in aging oocytes.
    Tom Lemonnier, Marie Dumont, Jiyeon Leem, Aysia Khan, Hossein Yazdkhasti, Vitaly Zimyanin, Ani Khutsaidze, Stefanie Redemann, Daniele Fachinetti, Binyam Mogessie.
      Maternal age is the primary risk factor for aneuploidy in mammalian oocytes, but the molecular mechanisms that preserve meiotic chromosome segregation fidelity during aging remain incompletely understood. Using ultrastructural analysis, we observe that spindle microtubules in aged mouse oocytes tend to exhibit increased misorientation and shorter interaction lengths, whereas microtubule number and density remain largely unchanged. We demonstrate that the levels of the key centromeric components CENP-A and CENP-C are reduced in oocytes from aged mice. Acute degradation of CENP-A during meiosis I affects CENP-C stability at centromeres and causes chromosome segregation errors in young oocytes, a phenotype not observed in mitosis. The expression of exogenous CENP-C rescues these defects via CENP-B-dependent centromere binding, supporting a link between centromere weakening and meiotic errors. This intervention also partially improves chromosome alignment in oocytes from older animals. Together, these findings implicate centromere weakening, alongside cytoskeletal disorganization, in the age-related decline in chromosome segregation fidelity in oocytes.
    DOI:  https://doi.org/10.1083/jcb.202606132
  2. Nat Commun. 2026 09 22. pii: 11028. [Epub ahead of print]17(1):
    Single-cell TimeLapse-seq reveals MTA is an essential retrotransposon orchestrating mouse zygotic genome activation.
    You Wu, Hanxi Shi, Rushuang Yan, Jiang Wu, Lei Yang, Lingfeng Xu, Xiaochen Kou, Yanhong Zhao, Xuelian Liu, Lingling Lai, Silin Tian, Yujie Hu, Qiyue Wang, Hong Wang, Shaorong Gao, Xiao-Ou Zhang, Yawei Gao.
      Transposable elements (TEs) are temporally activated during mammalian early embryogenesis and are closely linked to zygotic genome activation (ZGA), yet their nascent transcriptional dynamics remain incompletely resolved owing to limited sensitivity and maternal RNA background. Here, we develop single-cell TimeLapse sequencing (scTL-seq), enabling allele-resolved detection of nascent RNA in individual embryos. Applying scTL-seq to mouse ZGA, we generate a refined transcriptional atlas of genes and TEs and identify the pronuclear (PN) stage activated genes and TEs. We found that transcription at PN stage is largely contributed by the maternal genome and enriched for genes highly transcribed in germinal vesicle oocytes. Similarly, Mouse Transcripts type-A (MTA) elements are transcribed in oocytes and highly active in PN stage. MTA knockdown disrupts zygotic gene activation and dysregulates hundreds of TE subfamilies, resulting in 1-cell embryo arrest. Using nascent transcripts, we further identify 662 TE-driven chimeric transcripts and show that TEs are essential for regulating key developmental genes, including Nfya, Setd2 and Tead4. Finally, we identify maternal transcription factors, including NOBOX, as potential regulators of MTA activation. Together, our study provides a high-resolution nascent transcriptome landscape of mouse ZGA and reveals vital regulatory roles of MTA retrotransposon in orchestrating early embryonic development.
    DOI:  https://doi.org/10.1038/s41467-026-77750-3
  3. Nat Commun. 2026 09 21. pii: 10994. [Epub ahead of print]17(1):
    Single-oocyte proteome-transcriptome co-profiling reveals a role of dysregulated lactate metabolism in oocyte aging.
    Lanrui Cao, Hao Wu, Yirong Jiang, Yaxue Hou, Zhuo Yang, Yuan Wang, Peipei Ren, Panpan Zhao, Xiaofeng Ni, Shuai Liu, Na Kong, Xin Sheng, Yinli Zhang, Songying Zhang, Jianfeng Xiao, Cunqi Ye, Heng-Yu Fan, Yongcheng Wang, Xiaomei Tong, Qun Fang, Xudong Fu.
      The age-related decline in oocyte quality is a major risk factor for female infertility. Although transcriptome has been examined in aged oocytes, proteomic landscape, which reflects primary gene functional executors, remains largely unexplored. This gap limits our understanding of oocyte aging. To address this, we perform single-cell proteome/transcriptome co-profiling of GV/MII-aged oocytes from mice and humans, revealing species- and stage-specific proteomic/transcriptomic changes during oocyte aging. Strikingly, we observe uncoupled proteomic and transcriptomic alterations, indicating that proteomic changes in aged oocytes are not primarily driven by RNA levels. Furthermore, we capture molecular heterogeneity in aged oocytes and identify MCT4 as a candidate marker of oocyte aging. Functional studies suggest MCT4 contributes to aging-associated oocyte defects via lactate export, and its inhibition improves aged-oocyte quality. These findings indicate altered lactate metabolism as a candidate marker and intervention target for oocyte aging and underscore the value of our profiling in dissecting oocyte aging.
    DOI:  https://doi.org/10.1038/s41467-026-77910-5
  4. Cell Prolif. 2026 Oct 20. e70289
    No Female Germline Stem Cells Were Identified by Advanced Dual Recombinase-Based Lineage Tracing System.
    Yang Gao, Zhiming Shen, Xiuhong Cui, Min Chen, Mengyue Wang, Kui Liu, Fei Gao, Hongmei Wang.
      Whether female germline stem cells (fGSCs) exist in postnatal mammalian ovaries has been debated for decades. Since the fGSCs were first reported in 2004, a large number of studies have been conducted using different approaches. However, the persistent controversy surrounding the results has caused confusion among many researchers and clinicians. To clearly clarify this question, we developed advanced tracing system to label any possible fGSCs in adult female mice. Our results showed that no Stra8-expressing germ cells were detected in the ovaries of adult female mice using a long-term uninterrupted lineage tracing system under both physiological and pathological conditions. Furthermore, we adopted the interleaved reporter tracing system that allows mutually exclusive labelling of germ cells and non-germ cell populations while preventing potential secondary recombination. This approach revealed no evidence of de novo germ cell formation during postnatal life. Together, our findings provide the evidence that fGSCs and postnatal oogenesis do not exist under both physiological and pathological conditions in mouse models, therefore reinforcing the notion that the primordial follicle pool established perinatally serves as the primary source of oocytes through the entire reproductive lifespan.
    Keywords:   Stra8 ; Dual recombinase system; Female germline stem cells; Lineage tracing
    DOI:  https://doi.org/10.1111/cpr.70289
  5. Cell Mol Life Sci. 2026 Jul 24. pii: 388. [Epub ahead of print]83(1):
    Stella safeguards proteostasis via regulating UBE2D3 translation in the maternal-to-zygotic transition.
    Guorui Zhang, Minjie Ren, Guangyi Sun, Yilong Zhao, Na Zhang, Qiang Wang, Longsen Han.
      Ubiquitin-proteasome-mediated protein degradation is essential for maternal-to-zygotic transition, yet the maternal factors that safeguard ubiquitin-proteasome function remain unclear. Here, using a Stella-mutant mouse model, we demonstrate that Stella is required for global protein ubiquitination during early embryogenesis. Stella deficiency in oocytes leads to reduced ubiquitinated protein levels, impaired zygotic genome activation, and early developmental arrest. Proteomic and functional analyses identify UBE2D3 as the key E2 enzyme whose insufficiency underlies the ubiquitination defect. Mechanistically, Stella preserves YBX3 stability, thereby enabling YBX3-dependent translation of Ube2d3 mRNA. Consequently, Stella depletion destabilizes YBX3, diminishes UBE2D3 synthesis, and disrupts protein ubiquitination. Notably, overexpression of Ybx3 or Ube2d3 partially restores ubiquitinated protein levels, zygotic genome activation, and embryo development. These findings identify a previously unrecognized Stella-YBX3-UBE2D3 axis that ensures efficient maternal protein ubiquitination and zygotic genome activation, revealing a cytoplasmic mechanism by which maternal Stella governs proteostasis during maternal-to-zygotic transition.
    Keywords:  Maternal factor; Proteolysis; Translational control; Ubiquitination
    DOI:  https://doi.org/10.1007/s00018-026-06349-0
  6. Development. 2026 Oct 20. pii: dev.205811. [Epub ahead of print]
    Msps/XMAP215 Is Essential for Oocyte Specification in the Drosophila Ovary.
    Wen Lu, Margot Lakonishok, Hannah Neiswender, Graydon B Gonsalvez, Vladimir I Gelfand.
      Cell fate determination is fundamental to development. In the Drosophila ovary, a 16-cell germline cyst forms in which two pro-oocytes arise; one of the pro-oocytes is selected as the oocyte, while the remaining 15 cells differentiate into nurse cells. Here, we identify Mini spindles (Msps), a Drosophila XMAP215-family microtubule polymerase, as a key regulator of oocyte fate specification. msps mRNA and Msps protein are enriched in the pro-oocytes prior to oocyte specification. Elimination of Msps prevents oocyte specification and disrupts the accumulation of the oocyte marker Orb, producing egg chambers with 16 nurse cells. Conversely, optogenetic recruitment of Msps increases microtubule polymerization and promotes Orb accumulation in nurse cells, suggesting that Msps activity is sufficient to initiate key molecular events associated with oocyte specification. Furthermore, Msps associates with the germline-specific organelles, the spectrosome and fusome, and becomes asymmetrically distributed, biasing the two pro-oocytes toward oocyte fate. We propose that an Msps-dynein feedback loop amplifies small initial differences between the two pro-oocytes to specify a single oocyte.
    Keywords:   Drosophila ovary; Cell fate; Dynein; Germline cyst; Microtubules; Oocyte specification; Symmetry breaking; XMAP215
    DOI:  https://doi.org/10.1242/dev.205811
  7. Cell Commun Signal. 2026 Jul 22. pii: 563. [Epub ahead of print]24(1):
    Reduced insulin/IGF-1 signaling extends reproductive span through somatic gonadal collagen-mediated maintenance of oocyte and embryo quality in Caenorhabditis elegans.
    Neha Kaushik, Soumya Rastogi, Vaibhav Jain, Sonia Verma, Deepak Pandey, Mona Sharma, Ashutosh Halder, Simon Gregory, Neeraj Kumar.
       BACKGROUND: The somatic gonad plays a central role in supporting germline development and maintaining oocyte and embryonic integrity, both of which are essential for sustained reproductive function. With age, deterioration of somatic gonadal structures compromises germline support, leading to declines in oocyte morphology and increased embryonic abnormalities. The insulin/IGF-1 signaling (IIS) pathway regulates longevity and reproductive aging, and its reduction (rIIS) in the daf-2(e1370) mutant extends reproductive span in Caenorhabditis elegans. While prior work has largely focused on germline stem cells and oocyte maturation, the molecular mechanisms by which IIS preserves somatic gonadal architecture and thereby maintains oocyte and embryonic morphological integrity remain poorly understood. Elucidating how reduced IIS influences the somatic gonad can provide insights into the coordination of systemic aging pathways with tissue-specific mechanisms that sustain reproductive health.
    METHODS: We identified somatic gonad-enriched genes from temporal transcriptomic datasets of reduced IIS animals, highlighting collagens consistently upregulated with age. Using RNAi knockdowns in both systemic and somatic gonad-specific RNAi-sensitive strains of Caenorhabditis elegans, we examined effects on self-reproductive span, oocyte and embryonic morphology, and somatic gonad integrity. Age-associated morphological changes were assessed by differential interference contrast microscopy, and regulatory dependencies were tested via quantitative polymerase chain reaction following knockdown of key transcription factors.
    RESULTS: Several collagens were found to be essential for maintaining somatic gonadal architecture and preserving oocyte morphology during aging. Gonad-specific knockdown of these collagens caused structural deterioration, impaired oocyte and embryo quality, and accelerated reproductive decline. These defects occurred without a major reduction in total progeny number, suggesting that age-related reproductive loss arises primarily from tissue deterioration rather than immediate fertility impairment. Expression and function of these collagens were largely dependent on key transcription factors downstream of IIS.
    CONCLUSION: Our findings uncover a previously unrecognized role for somatic gonadal collagens in preserving reproductive function under IIS. By maintaining gonadal architecture and sustaining oocyte and embryonic morphological integrity, these collagens act as downstream effectors of IIS-mediated reproductive longevity. Targeting gonadal collagen networks may therefore represent a potential strategy to mitigate age-related reproductive decline and warrants further investigation in higher-order models.
    Keywords:   Caenorhabditis elegans ; Collagens; Embryo; Insulin signaling; Oocyte; Reproductive aging; Somatic gonads; Transcriptomics
    DOI:  https://doi.org/10.1186/s12964-026-03069-7
  8. Nat Genet. 2026 Oct 19.
    Establishing Polycomb regulatory landscapes in human early development.
    Xiaoyu Hu, Chuanxin Zhang, Bofeng Liu, Fangnong Lai, Shuiying Ma, Zhenzhen Hou, Qizhe Shao, Ling Liu, Xukun Lu, Guanling Yu, Hui Liu, Zhen Yang, Ning Wang, Xi Wu, Zili Lin, Lijuan Wang, Yongli Shan, Guangjin Pan, Di Chen, Bo Zhang, Lei Jin, Han Zhao, Keliang Wu, Zi-Jiang Chen, Wei Xie.
      H2AK119ub (H2Aub) and H3K27me3, which are deposited by the Polycomb group (PcG) complexes PRC1 and PRC2, respectively, cooperatively repress developmental genes. However, in human preimplantation embryos, H3K27me3 undergoes genome-wide erasure and subsequent restoration. How H3K27me3 is reestablished and whether PcG complexes still regulate gene repression in human embryos remain unknown. Here, we profiled H2Aub dynamics from human gametes to blastocysts. H2Aub emerges in GC-rich regions as early as the two-cell stage, progressively accumulates at both active and inactive genes, and further culminates at PcG targets in later stages. H3K27me3 is weakly correlated with H2Aub in oocytes and two-cell embryos but colocalizes with H2Aub at H3K4me3-depleted, inactive PcG targets in blastocysts. Loss of H2Aub abolishes H3K27me3 reestablishment at PcG targets causing moderate derepression, accompanied by ectopic H3K27me3 deposition and impaired embryonic development. Finally, H2Aub and DNA methylation cooperatively maintain H3K27me3 patterning in human embryonic stem cells. Therefore, H2Aub-dependent H3K27me3 deposition underlies the earliest establishment of Polycomb repression in humans.
    DOI:  https://doi.org/10.1038/s41588-026-02764-y
  9. Biol Reprod. 2026 Oct 21. pii: ioag237. [Epub ahead of print]
    Insights into Cytoplasmic Maturation in Human Oocytes: Organelle Dynamics, Ionic Homeostasis, and Translational Regulation.
    Laura Burillo, Marga Esbert.
      Oocyte maturation is a fundamental biological process required for fertilization and the acquisition of developmental competence. Although nuclear events such as meiotic resumption and chromosomal segregation have historically attracted more scientific interest, cytoplasmic remodeling constitutes an equally essential determinant of oocyte quality. This review synthesizes recent evidence on the dynamic reorganization of organelles, regulation of protein synthesis and post-translational modifications, ionic homeostasis, and the distinct cytoplasmic signatures that characterize in vivo and in vitro maturation. During oocyte maturation, the endoplasmic reticulum (ER), mitochondria, and cortical granules undergo stage-specific structural and spatial reorganization. Changes in maternal protein abundance and intracellular zinc (Zn2+) and calcium (Ca2+) signaling also accompany meiotic progression and acquisition of developmental competence. In the context of assisted reproduction, a subset of oocytes retrieved after controlled ovarian stimulation remains immature, typically at the germinal vesicle (GV) or metaphase I (MI) stage, prompting the use of rescue in vitro maturation (r-IVM) protocols to complete their development. Evidence suggests that such oocytes matured in vitro may display aberrant cytoplasmic architecture, impaired organelle distribution, and reduced functional competence, features that may account for the suboptimal outcomes frequently reported after r-IVM. Advancing our understanding of these cytoplasmic processes is likely to facilitate the refinement of in vitro maturation systems, improve oocyte utilization, and ultimately enhance the efficacy of clinical interventions in human reproduction.
    Keywords:  cytoplasmic changes; in vitro oocyte maturation; oocyte maturation; oocyte organelles
    DOI:  https://doi.org/10.1093/biolre/ioag237
  10. Nat Commun. 2026 09 17. pii: 10929. [Epub ahead of print]17(1):
    Multiplexed embryo profiling links cellular state to zygotic genome activation in single cells.
    Max Hess, Marvin F Wyss, Edlyn Wu, Gian-Marco Schaniel, Joel Lüthi, Chiara Rebagliati, Daniel Hannuschke, Nadine L Vastenhouw, Darren Gilmour, Shayan Shamipour, Lucas Pelkmans.
      Multicellular self-organization depends on interactions across multiple length scales, yet mapping protein states at high spatial resolution in whole-mount embryos remains challenging. Here, we introduce high-throughput 3D in toto iterative immunofluorescence imaging (3D-4i) and a dedicated computer vision pipeline to quantify morphological and molecular features from subcellular to whole-embryo scales across hundreds of samples. Applying this pipeline to early zebrafish embryos undergoing mid-blastula transition, we determine the cell cycle phase for each cell across the embryo, and uncover the spatiotemporal dynamics by which global meta-synchronous mitotic waves transition to cell cycle desynchronization. Using statistical analysis, we find that the cell cycle phase is the major source of variability in transcription within a division cycle, and combining this with the analysis of key transcription factors and chromatin modifier state, included in our multiplexed dataset, enables accurate prediction of transcriptional output during zygotic genome activation in individual cells. Together, these findings establish 3D-4i as a powerful approach for quantifying multimodal, multiscale biological processes underlying multicellular self-organization.
    DOI:  https://doi.org/10.1038/s41467-026-77784-7
  11. Sci Adv. 2026 Oct 23. 12(43): eaef7931
    RanGAP1 coordinates the ER-lamina interface to drive de novo nuclear envelope reassembly in mouse embryos.
    Xiao-Jie Zhang, Cheng-Jie Zhou, Chun-Ru Song, Meng-Lei Feng, Fang-Rui Xue, Dui Sun, Qi Yang, Kang Ding, Zhao-Yu Jiang, Cheng-Guang Liang.
      Nuclear envelope (NE) reassembly is essential for the zygote-to-totipotency transition in mammalian embryos. Beyond its classical roles in nuclear transport and maintenance of the RanGTP gradient, the function of RanGAP1 in embryonic NE reassembly has remained elusive. Here, we show that RanGAP1 localizes to the early embryonic NE, driving reassembly via a distinct structural mechanism. Trim-Away-mediated RanGAP1 depletion causes two-cell stage arrest and severe NE defects, including nuclear pore complex (NPC) loss, failed reassembly, and aberrant "fishnet" membrane structures. Mechanistically, RanGAP1 establishes a structural paradigm for endoplasmic reticulum (ER)-lamina coupling by recruiting Lamin A/C, B1, and B2 to the ER for coassembly. The acidic domain and SUMO-1 modification at Lys526 (K526) are essential for the NPC localization of RanGAP1. Thus, RanGAP1 orchestrates nuclear lamina (NL) assembly by targeting lamins to the ER. These findings uncover mechanisms of NE reassembly that are critical for early embryogenesis and provide insights into NE-related developmental disorders.
    DOI:  https://doi.org/10.1126/sciadv.aef7931
  12. Sci Adv. 2026 Oct 23. 12(43): eaeh1087
    DMRT1 is required at two steps of ovarian differentiation in rabbits.
    Emilie Dujardin, Francis Poulat, Ivan Barberá Aura, Aurélie Dewaele, Marjolaine André, Jennifer McKey, Stéphanie Le Gras, Anne Frambourg, Luc Jouneau, Darío G Lupiáñez, Béatrice Mandon-Pépin, Eric Pailhoux.
      The transcription factor Doublesex and Mab-3 Related Transcription Factor 1 (DMRT1) is essential for testis differentiation and male fertility, but less is known about its potential involvement in ovarian differentiation. In mice, Dmrt1-/- females are fertile, although they show a reduction of Stra8 expression. Using our DMRT1 mutant rabbit model, we analyzed ovarian differentiation when DMRT1 expression is abolished. First, we observed that during early gonadal development, DMRT1-/- gonads display a specific transcriptome different from control ovaries and control testes. Second, we assessed the infertility phenotype of mutant females. DMRT1 is highly expressed in germ cells until meiosis initiation, and its disruption leads to a down-regulation of key genes involved in the meiotic process. Chromatin immunoprecipitation sequencing data highlighted that DMRT1 can bind these genes in the rabbit ovary. Our study using the rabbit model shows that in addition to its role in testicular differentiation, DMRT1 has two important functions in ovarian differentiation: an initial involvement in the differentiation of somatic cells and a pivotal role in the differentiation of germ cells. Our data suggested that DMRT1 could be considered in human health as a gene necessary for female fertility.
    DOI:  https://doi.org/10.1126/sciadv.aeh1087
  13. Trends Endocrinol Metab. 2026 Oct 22. pii: S1043-2760(26)00241-9. [Epub ahead of print]
    The postpartum recovery window as a determinant of maternal aging.
    Stephen M Albright, Jesse R Poganik.
      Higher parity predicts an elevated mortality risk in many cohorts, yet the association is inconsistent across populations and poorly explained by existing mechanistic accounts. Accumulating evidence indicates that pregnancy transiently accelerates biological age and that the postpartum period represents a recovery window during which this acceleration partially reverses. When a subsequent pregnancy begins before recovery is complete, this normalization is truncated and the aging burden may compound across successive pregnancies. We propose that the interpregnancy interval, as the determinant of how much recovery occurs between pregnancies, is the missing variable linking reproductive history to the long-term maternal aging trajectory. We develop falsifiable predictions, identify the study designs needed to test them, and argue that reproductive spacing may be a modifiable determinant of the lifelong aging trajectory.
    Keywords:  biological age; epigenetic clocks; interpregnancy interval; parity; postpartum recovery; reproductive aging
    DOI:  https://doi.org/10.1016/j.tem.2026.09.002
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