bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–07–26
nine papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. The Drosophila ovary produces two waves of adult follicles and a novel pupal wave that turns over.
  2. Integrated Single-cell Proteomic and Transcriptomic Landscape of Mouse Folliculogenesis.
  3. Probing the Ovarian Microenvironment: Methods for Isolation, 2D Culture, and Organoid Culture of Mouse Ovarian Somatic Cells.
  4. GCL pruning of PIP3 establishes the soma-germline boundary.
  5. SP1 controls zygotic genome activation and morula-to-blastocyst transition in mouse embryos.
  6. Single-cell atlas of the mouse ovary reveals molecular drivers of aging and senescence during the estropausal transition.
  7. SYCP2 recruits HORMAD2 to chromosome axes for unsynapsed chromatin silencing and synapsis surveillance in meiosis.
  8. Comparative single-nucleus transcriptomics reveals asymmetric evolution of the Drosophila male and female germlines.
  9. Annulate lamellae - an underexplored cellular structure.
  1. Development. 2026 Jul 23. pii: dev.205668. [Epub ahead of print]
    The Drosophila ovary produces two waves of adult follicles and a novel pupal wave that turns over.
    Wayne Yunpeng Fu, Allan C Spradling.
      Ovarian follicles in most species are assumed to develop using a single pathway. However, in Drosophila pupae, lineage tracing 2,937 single-cell clones identified three follicle "waves" that follow distinct programs arrayed anterior to posterior in the germarium and developing ovarioles. 40 primordial germ cells (PGCs) become anterior germline stem cells (GSCs) that produce "wave 2" follicles throughout adulthood. 100 PGCs posterior to wave 2 develop into "wave 1.5" follicles that form the earliest laid eggs. Different follicle stem cells (FSCs) sequentially occupy the same two niches timed to provide both waves with specific follicle cells, consistent with programmed differences between waves 2 and 1.5. "Wave 1" PGCs located even further posterior proliferate, form cysts, interact with swarm cells, degenerate, break from the ovary 22-26 hours after puparium formation, and release lipid-enriched vacuoles. Some testis germ cells behave similarly. We speculate that wave 1 germ cells contribute directly or indirectly to the pharate adult ecdysone pulse that mediates adult development and sex-specific neural remodeling. Why Drosophila follicle waves generally resemble those clarified recently in mouse preadult ovaries merits additional study.
    Keywords:  Drosophila melanogaster ; Follicle stem cell; Germ cell; Germline stem cell; Ovarian follicle wave; Pupal ovary
    DOI:  https://doi.org/10.1242/dev.205668
  2. Genomics Proteomics Bioinformatics. 2026 Jul 23. pii: qzag068. [Epub ahead of print]
    Integrated Single-cell Proteomic and Transcriptomic Landscape of Mouse Folliculogenesis.
    Hongchao Li, Xinshuai Zhang, Huimin Kang, Yun Yang, Xinyu Xiao, Yan Wang, Bin Fu, Jie Chen, Xinwen Dong, Yuanjun Zhai, Jing Yang, Jianming Ying, Fuchu He, Yang Li, Xiaowen Wang.
      Folliculogenesis is a complex process essential to female fertility, characterized by multifaceted communication between oocytes and granulosa cells (GCs). While transcriptional regulation during folliculogenesis has been extensively studied, the proteomic landscape remains largely unexplored. Here, we profiled both the proteomic and transcriptomic landscapes of single oocytes and their surrounding mini-bulk GCs across four consecutive stages, from secondary to preovulatory follicles. Integrated dual-omics analysis provided a high-resolution characterization of cell type-specific transcriptional and proteomic changes. Proteomic profiling revealed coordinated metabolic programs, in which oocytes shift toward lipid storage while GCs enhance energy production and steroidogenic metabolism to support oocyte maturation. These metabolic changes in oocytes were accompanied by dynamic remodeling of mitochondrial organization. In addition, we identified novel transcription factors involved in regulating folliculogenesis, as well as a SATB1-centered regulatory network that may reflect preparatory chromatin remodeling preceding zygotic genome activation. Furthermore, GDF9-BMPR2 signaling progressively increased from the secondary stage to the preovulatory stage, indicating strengthened intercellular communication between oocytes and GCs. Together, these findings provide mechanistic insights into oocyte development and follicle growth, with potential implications for novel fertility treatments and diagnostic strategies.
    Keywords:  Folliculogenesis; Intercellular communication; Single-cell proteome; Single-cell transcriptome; Transcription factor regulatory network
    DOI:  https://doi.org/10.1093/gpbjnl/qzag068
  3. J Vis Exp. 2026 Jul 03.
    Probing the Ovarian Microenvironment: Methods for Isolation, 2D Culture, and Organoid Culture of Mouse Ovarian Somatic Cells.
    Shweta S Dipali, Aubrey Converse, Madison Q Gowett, Emily J Zaniker-Gomez, Madeline J Perry, Francesca E Duncan.
      The ovary consists of heterogeneous populations of somatic cells, both within the follicle and the surrounding stroma, which are critical to support ovarian function and for the generation of high-quality gametes. We report methods for isolating somatic cells from mouse ovaries, including endothelial, epithelial, steroidogenic, stromal, and immune cells. When these primary ovarian somatic cells are plated and cultured in a traditional 2D culture system, the cellular heterogeneity, organization, as well as cell-cell and cell-matrix interactions typically found in the ovary are lost. Thus, we also describe how to generate mouse ovarian somatic organoids using a scaffold-free approach. These organoids self-assemble, maintain diverse cell populations, and produce extracellular matrix and secreted factors, including cytokines. Organoids can be utilized for co-culture experiments and can be maintained in culture for at least 3 weeks with high viability. Overall, these models enable interrogation of ovarian physiology and pathology from the somatic cell perspective.
    DOI:  https://doi.org/10.3791/71001
  4. J Cell Biol. 2026 Sep 07. pii: e202604036. [Epub ahead of print]225(9):
    GCL pruning of PIP3 establishes the soma-germline boundary.
    Mariyah Saiduddin, Juhee Pae, Asier M Vidal, Martin L Alani, Ruth Lehmann.
      Primordial germ cells (PGCs) are the first cells specified in the Drosophila embryo and are precursors to the germline. Their formation requires suppression of somatic fates, achieved by degrading the receptor tyrosine kinase Torso at the posterior pole through the ubiquitin ligase adaptor germ cell-less (GCL). Although Torso is known to antagonize PGC formation, the underlying mechanisms remained unclear. Here, we combine optogenetic Ras activation and Ras effector loop mutants to show that Ras suppresses PGC formation independently of the canonical Raf/MEK/ERK pathway. We identify an unexpected early role for Torso in activating phosphoinositide 3-kinase (PI3K), generating membrane domains enriched in phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Elevated PI3K activity disrupts PGC formation, while reduced PI3K activity creates ectopic PGCs. We demonstrate that GCL remodels the posterior pole membrane by suppressing Torso-dependent PI3K activation. Clearing PIP3 enables myosin II enrichment, allowing for PGC formation. Together, our findings reveal how antagonistic Torso and GCL activities establish the soma-germline boundary by organizing cortical lipids.
    DOI:  https://doi.org/10.1083/jcb.202604036
  5. Reproduction. 2026 Jul 20. pii: xaag087. [Epub ahead of print]
    SP1 controls zygotic genome activation and morula-to-blastocyst transition in mouse embryos.
    Ai Di, Huang Rong, Wang Fang, Cui Zhi, An Xinglan, Ziyi Li, Zhu Haibo, Sheng Zhang.
      Specificity protein 1 (SP1) is the most active member of the specificity protein and Krüppel-like factor (Sp/KLF) family and is widely expressed across all mammalian cell types. However, more detailed studies on the role of SP1 in preimplantation embryonic development are needed. Here, we analyzed the role of SP1 in the development of preimplantation mouse embryos through supplementation with a small molecular inhibitor (plicamycin) and microinjection of Sp1 siRNA. We found that SP1 was indispensable for zygotic genome activation (ZGA) and the morula-to-blastocyst transition. Plicamycin supplementation arrested embryo development at the 2-cell stage and resulted in aberrant RNA polymerase II preconfiguration. Sp1 expression knockdown by Sp1 siRNA microinjection caused most embryos to arrest at the morula stage, and the expression of NANOG, POU5F1 and CDX2 significantly decreased. Both plicamycin supplementation and Sp1 siRNA microinjection decreased embryonic H3K4me3 levels and increased H3K9me3 levels. Moreover, when Sp1 was overexpressed, the embryos were arrested at the 2-cell stage, the H3K4me3 level increased, and the H3K9me3 level decreased. In conclusion, our findings demonstrate that SP1 is crucial for mouse preimplantation embryonic development through the regulation of gene expression and histone modifications.
    Keywords:  Morula to blastocyst transition; Mouse; Preimplantated embryonic development; SP1; Zygotic genome activation
    DOI:  https://doi.org/10.1093/reprod/xaag087
  6. Proc Natl Acad Sci U S A. 2026 Jul 28. 123(30): e2600323123
    Single-cell atlas of the mouse ovary reveals molecular drivers of aging and senescence during the estropausal transition.
    Xifan Wang, Jiping Yang, Chen Jin, Xizhe Wang, Daniela Contreras, Melody Devos, Maggie M Kane, Michael G Rosenfeld, Yousin Suh.
      Reproductive aging in mice leads to estropause, characterized by estrous cycle irregularity and eventual cessation, yet its underlying mechanism remains unclear. Here, we present a comprehensive single-cell atlas of mouse ovaries across precisely defined reproductive stages-from young (regular cycling) through the estropausal transition (regular vs. irregular cycling) to post-estropause (acyclic)-and of ovary-specific senescent cells defined by high senescence-associated β-galactosidase activity. We mapped transcriptomic dynamics of ovarian aging and characterized the molecular features of ovarian senescent cells. Our analyses revealed that during the estropausal transition, irregularly cycling ovaries exhibited accelerated aging and cellular senescence features compared with regularly cycling counterparts, including increased transcriptional noise, altered conserved aging pathways such as oxidative phosphorylation and proteostasis, hormone dysregulation in granulosa cells, and elevated expression of the senescence marker Cdkn1a and senescence-associated secretory phenotype factors. This atlas delineates the cellular and molecular hallmarks of mouse ovarian aging and ovary-specific senescent cells, providing a resource for understanding the mechanisms underlying the estropausal transition.
    Keywords:  aging; cellular senescence; estropausal transition; ovary; single-cell RNA-seq
    DOI:  https://doi.org/10.1073/pnas.2600323123
  7. Nat Commun. 2026 Jul 23. pii: 7122. [Epub ahead of print]17(1):
    SYCP2 recruits HORMAD2 to chromosome axes for unsynapsed chromatin silencing and synapsis surveillance in meiosis.
    Kavya Raveendran, Sarai Valerio-Cabrera, Arkasarathi Gope, Vladyslav Telychko, Geen George, Christin Richter, Tanja Scholte, Matthias Weigel, Anastasiia Bondarieva, Andreas Petzold, Andreas Dahl, Kevin D Corbett, Attila Tóth.
      Faithful chromosome segregation during meiosis requires accurate recombination and synapsis of homologous chromosomes. These processes are monitored in mammals by checkpoints involving the meiotic HORMA-domain proteins HORMAD1 and HORMAD2, which bind unsynapsed chromosome axes and promote activation of the DNA damage-response kinase ATR independently of DNA double-strand breaks (DSBs). However, the in vivo mechanism for axial HORMAD1 and HORMAD2 recruitment and its relevance to checkpoint signaling remain unclear, although the chromosome-axis component SYCP2 has been proposed to contain a candidate HORMAD-binding closure motif (CM). We show that deletion of the SYCP2 CM disrupts SYCP2-HORMAD2 complexes and selectively prevents HORMAD2 axis binding without affecting axis assembly, recombination, or axial HORMAD1 recruitment. Consequently, ATR accumulation and signaling on unsynapsed axes are reduced, and the prophase checkpoint malfunctions, manifesting in aberrant elimination of synapsis-proficient spermatocytes and persistence of asynaptic oocytes, which reflect sex-specific characteristics of checkpoint mechanisms. The phenotypes of SYCP2-CM-deficient and HORMAD2-null mice are indistinguishable, establishing the requirement for HORMAD2 axis recruitment in synapsis surveillance. We propose that axial recruitment generates a HORMAD2 scaffold that drives clustering-mediated ATR network activation independently of DSBs, thereby linking chromosome-axis architecture to synapsis quality control in mammalian meiosis.
    DOI:  https://doi.org/10.1038/s41467-026-75839-3
  8. PLoS Biol. 2026 Jul;24(7): e3003869
    Comparative single-nucleus transcriptomics reveals asymmetric evolution of the Drosophila male and female germlines.
    Imtiyaz E Hariyani, Sudeshna Das, Emma M Le, Carmen Gamero-Castano, Tina Soroudi, Joshua Choi, Spring Momeni, Justin C Kim, Rongying Lu, Vivek Swarup, José M Ranz.
      Reproductive organs vary widely across species yet share conserved cell types that produce gametes, sustaining species' perpetuation. However, tissue-level comparisons mask critical differences among cell types, obscuring where evolutionary divergence occurs even between closely related species. We quantified expression divergence at cell-type resolution between two sibling species, Drosophila melanogaster and D. simulans, while disentangling adaptive and nonadaptive evolutionary mechanisms. We built a comparative single-nucleus transcriptomic atlas of over 100,000 nuclei from testes and ovaries of both species. Our analysis revealed sharply heterogeneous divergence across testis cell types, contrasting with a broader conservation across ovary cell types. Notably, in both organs, ~40% of genes showing interspecific differences did so in only one cell type. In the testis, spermatogonia were largely conserved, whereas divergence peaked in primary spermatocytes with extensive rewiring of coexpression modules linked to microtubule and mitochondrial functions. In the ovary, expression was largely conserved, except in early germline and late follicle cells, which showed shifts in oogenesis and cell-cycle-related coexpression modules. Divergent cell types in both tissues were enriched for evolutionarily young genes with narrow expression breadth and faster protein evolution rates. Additionally, the ovary exhibited a faster-X effect consistent with adaptive evolution. These findings reveal a fundamental asymmetry in how male and female germlines evolve, with functional constraints relaxed in specific testis cell types but broadly maintained across the ovary. Our work provides an evolutionary framework explaining how core reproductive functions are safeguarded during species diversification while identifying germline cells that drive evolutionary change.
    DOI:  https://doi.org/10.1371/journal.pbio.3003869
  9. J Cell Sci. 2026 Jul 15. pii: jcs264633. [Epub ahead of print]139(14):
    Annulate lamellae - an underexplored cellular structure.
    Lizanne Oliveira, Jomon Joseph.
      Annulate lamellae (AL) are endoplasmic reticulum (ER) subdomains harbouring a subset of nucleoporins (Nups), the proteins that assemble into the nuclear pore complexes (NPCs) on the nuclear envelope (NE). AL have been observed in a variety of cell types, including oocytes, spermatids, embryonic cells, somatic cells and tumour cells, as well as in multiple cell lines. Some studies propose that AL derive from the NE, whereas studies in Drosophila egg chambers indicate that AL can assemble through differential condensation of soluble Nups, thus implying that modes of AL assembly can vary depending on the cell type and cell physiology. Although little is known about the functions of AL, they have conventionally been implicated in NPC assembly and NE homeostasis. However, emerging evidence suggests additional roles for AL in the regulation of nucleocytoplasmic transport (NCT) and mRNA translation. Additionally, AL might regulate cytosolic processes such as ER-mitochondrial connectivity, ER Ca2+ release, and activation of specific proteins. AL remodelling is also associated with development, disease and infection, further emphasising a key role for AL in a variety of cellular processes and contexts.
    Keywords:  Acute necrotizing encephalopathy-1; Annulate lamellae; Ca2+ homeostasis; ERMCS; ER–mitochondria contact site; NPC; NPC-phagy; Neurodegenerative diseases; Nuclear pore complex; Nucleocytoplasmic transport; Nucleoporins; Nups; miRNA
    DOI:  https://doi.org/10.1242/jcs.264633
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