bims-cebooc Biomed News
on Cell biology of oocytes
Issue of 2026–06–07
eighteen papers selected by
Gabriele Zaffagnini, Universität zu Köln
  1. Somatic cells compartmentalise their carbohydrate metabolism to sustain germ cell survival.
  2. Asymmetric attrition and secondary chromosome destabilization after double-strand breaks in human embryonic development.
  3. Nucleolar Dynamics During Oogenesis.
  4. Prefoldin function links meiotic chromosome segregation with cellular remodeling and reveals tubulin sensitivity of the meiotic spindle.
  5. Embryo-scale Visual Cell Sorting reveals a conserved transcriptomic signature of nucleolar size linked to proteostasis.
  6. Live Imaging of Epithelial Phagocyte Differentiation in the Drosophila Ovary Reveals Transient and Novel Behaviors.
  7. Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.
  8. Building a resilient ovarian reserve: Early soma-oocyte interactions.
  9. Activation of primordial follicles.
  10. The SPN-4 Rbfox RNA-binding protein selects maternal mRNAs for CCR4-NOT-dependent clearance in early Caenorhabditis elegans embryos.
  11. ​​Deletion of Ybx1 results in germ cell hypoplasia in mouse embryos.
  12. Mechanisms of germ-soma communication during follicular growth.
  13. The ovarian stroma as a key regulator of follicular development and gamete quality across the reproductive lifespan.
  14. In the Drosophila germline H2Av and Arp6 suppress transposons by driving piRNA pathway expression.
  15. Impact of cancer immunotherapies on oocyte health and ovarian function.
  16. Developmentally programmed changes in cytoplasmic mechanics revealed by active microrheology in C. elegans embryos.
  17. Conditional replacement of the mouse LH receptor with GFP, enabling imaging of cell migration during ovulation.
  18. Segmental specification of the human female fetal reproductive tract revealed by spatiotemporal dynamics.
  1. EMBO J. 2026 Jun 04.
    Somatic cells compartmentalise their carbohydrate metabolism to sustain germ cell survival.
    Diego Sainz de la Maza, Holly Jefferson, Celine I Brucker, Sonia Paoli, Marc Amoyel.
      To ensure success in reproduction, organisms dedicate substantial resources to supporting the germline. In testes, somatic gonadal cells form a barrier that isolates germ cells from circulating nutrients, raising the question of how germ cell metabolism is sustained and how somatic cells ensure that sufficient resources are directed to the germline. Here, we use lineage-specific genetic manipulations and metabolite reporters to show that Drosophila somatic gonadal cells break down circulating sugars to produce and shuttle lactate to germ cells in vivo, thus sustaining their survival. Further, we uncover that somatic cells ensure the allocation of carbohydrate metabolites specifically to germ cell support and that increasing autonomous consumption of carbohydrates in somatic cells increases germ cell death. Thus, germ cell survival depends on functional metabolic compartmentalisation within gonadal somatic support cells.
    DOI:  https://doi.org/10.1038/s44318-026-00815-y
  2. Nat Commun. 2026 Jun 03.
    Asymmetric attrition and secondary chromosome destabilization after double-strand breaks in human embryonic development.
    Jenna Turocy, Stepan Jerabek, Woonyung Hur, Jimin Kim, Shuangyi Xu, Qiaojin Zhao, Jia Xu, Alex Robles, Xiangyi Liu, Nathan Treff, Diego Marin, Anna-Katerina Hadjantonakis, Dieter Egli.
      DNA repair in human embryos is poorly understood, and double-strand breaks (DSBs) can cause chromosome loss. We show that chromosomal alterations relative to an induced DSB are asymmetric: acentric arms show complementary gains and losses, while centric arms are biased toward losses. Centromeric to the cut site secondary breakage and attrition is extensive. In contrast, break sites at acentric arms are conserved with no secondary breakage. These differences reflect differential forces at the mitotic spindle. Telomeric arms detach from the pro-metaphase spindle while centric truncated chromosomes lag during anaphase, suggesting that the DSB impedes sister chromatid separation. Secondary breakage near the centromere concordant with extensive attrition at the DSB site indicates a DSB can destabilize a chromosome without end-joining of sister chromatids. These results highlight the risks of chromosomal-scale changes in CRISPR-Cas9 genome editing and show that a single DSB can destabilize a human embryo chromosome independent of fusion-breakage cycles.
    DOI:  https://doi.org/10.1038/s41467-026-73891-7
  3. bioRxiv. 2026 May 20. pii: 2026.05.19.726235. [Epub ahead of print]
    Nucleolar Dynamics During Oogenesis.
    Ruoyu Li, Grace McKown, Dai Tsuchiya, Mark Mattingly, Anna Galligos, Michay Diez, Jui Feng Lu, Mary C McKinney, Sean McKinney, Boris Rubinstein, Timothy J Corbin, Melainia McClain, Carrie Carmichael, Victoria A Hassebroek, Stephanie H Nowotarski, Jennifer L Gerton, Kamena K Kostova.
      Ribosome biogenesis is a conserved and highly regulated process that starts in the nucleolus, a membrane-less multi-phase organelle. Although the architecture of the nucleolus is known to change due to perturbations, how nucleolar organization is modulated during physiological processes to meet changing translational demands remains unclear. Here, we use zebrafish oogenesis as a developmental context requiring a rapid expansion of translational capacity to investigate the regulation of nucleolar architecture. We show nucleoli undergo coordinated changes in number, size, subnuclear localization, and layering throughout oogenesis. We further demonstrate that nucleoli form around extrachromosomal DNA circles that contain the rDNA locus. Notably, mouse oocytes undergo similar developmental changes in nucleolar layering and phase organization, indicating that remodeling of nucleolar condensates is a conserved feature of oogenesis. These findings reveal previously unexplored regulation of nucleolar architecture as developmental adaptations to changing biosynthetic needs.
    DOI:  https://doi.org/10.64898/2026.05.19.726235
  4. bioRxiv. 2026 May 20. pii: 2026.05.20.726416. [Epub ahead of print]
    Prefoldin function links meiotic chromosome segregation with cellular remodeling and reveals tubulin sensitivity of the meiotic spindle.
    Naohiro Kuwayama, Benjamin S Styler, Bojana Stekovic, Helen Sakharova, Liana Lareau, Marko Jovanovic, Elçin Ünal, Gloria A Brar.
      Faithful chromosome segregation is essential for producing viable gametes during meiosis, a specialized type of cell division compared to mitosis. Unlike mitosis, meiosis involves two consecutive chromosome segregation events without an intervening round of DNA replication. Here we identify Gim3, a subunit of the ubiquitously expressed and conserved prefoldin complex, as a critical regulator of meiotic but not mitotic chromosome segregation in budding yeast. Loss of Gim3 causes profound defects in chromosome segregation and gamete viability through reduced tubulin protein levels, which are also associated with reduced spindle length. In mitosis, however, GIM3 deletion minimally affects spindle length and chromosome segregation, despite similarly reduced tubulin levels in both contexts, highlighting a previously unrecognized difference between the sensitivity of meiotic and mitotic spindles to tubulin abundance. In addition to chromosome segregation defects, gim3Δ cells exhibit aberrant meiotic cellular remodeling, including defects in exclusion of age-associated protein aggregates from newly forming gametes. Importantly, experimentally induced meiotic chromosome mis-segregation similarly disturbs cellular remodeling. Together, our findings identify Gim3 as a key factor required for maintaining chromosome segregation integrity during meiosis and reveal a previously unrecognized link between chromosome segregation and meiotic cellular remodeling.
    DOI:  https://doi.org/10.64898/2026.05.20.726416
  5. bioRxiv. 2026 May 26. pii: 2026.05.25.727721. [Epub ahead of print]
    Embryo-scale Visual Cell Sorting reveals a conserved transcriptomic signature of nucleolar size linked to proteostasis.
    Hyeon-Jin Kim, Sriram Pendyala, Josephine Lin, Tony Cooke, Gang Li, William Stafford Noble, Xinxian Deng, Christine M Disteche, Cole Trapnell, Douglas M Fowler.
      Nucleoli, nuclear speckles and other compartments regulate transcription, RNA processing, and chromatin organization within the nucleus, yet the relationship of their morphology to developmental gene expression programs in vivo is poorly understood. Here, we develop a high-throughput Visual Cell Sorting (VCS) workflow for fixed cells and nuclei that combines antibody-based photoconversion; GPU-accelerated, real-time image analysis; and three-level single-cell combinatorial indexing RNA-seq (sci-RNA-seq3) to link nuclear compartment morphology to single-nucleus transcriptomes at embryo scale. We use VCS to analyze and sort over 1 million mouse embryo-derived nuclei by nucleolar, nuclear speckle, or nuclear size and construct a transcriptional atlas annotated with nuclear compartment phenotypes. Nuclear compartment size varies both between and within lineages and is shaped by proliferation and differentiation. In extracellular matrix protein-producing cell types such as fibroblasts, chondrocytes, and osteoblasts, nucleolar enlargement is uncoupled from cell cycle, and in erythroid cells exhibit a sharp nucleolar contraction preceding cell-cycle exit. We identify a 41-gene transcriptional signature whose expression tracks nucleolar size, enriched for ribosome biogenesis, mitochondrial metabolism, unfolded protein response, stress granule, and ubiquitin-proteasome pathway components. We used this nucleolar transcriptional signature to annotate mouse, zebrafish and human developmental atlases with nucleolar size information, revealing a conserved coupling between nucleolar activity and proteostasis programs. Our work establishes Visual Cell Sorting as a scalable platform for mapping image-based phenotypes to molecular programs; details the relationship between nuclear compartment phenotypes and development; and provides a transcriptional signature to estimate nucleolar size from existing single-cell datasets.
    DOI:  https://doi.org/10.64898/2026.05.25.727721
  6. bioRxiv. 2026 May 25. pii: 2026.05.21.726826. [Epub ahead of print]
    Live Imaging of Epithelial Phagocyte Differentiation in the Drosophila Ovary Reveals Transient and Novel Behaviors.
    Caique Almeida Machado Costa, Cristian Santiago Santiago, Jie Sun, Yi-Chun Huang, Wu-Min Deng.
      The transformation of epithelial cells into Non-Professional Phagocytes (NPPs) is a conserved and versatile adaptation that occurs in response to immune challenges, tissue remodeling, and apoptotic debris clearance. In the Drosophila melanogaster ovary, follicle cells (FCs) acquire phagocytic capabilities under stress, providing a powerful model to study this process. Using time-lapse live imaging, we captured dynamic behaviors associated with FC-to-NPP differentiation that are too transient to detect by static imaging. Our approach confirmed established features, including germline cell death, cytoplasmic expansion, and debris engulfment, and revealed previously unrecognized capabilities. These include a gradual increase in JNK pathway activation, after which NPPs exhibit collective migration toward dying germline cells, epithelial delamination, long-range target capture through pseudopodial extensions, and the engulfment of neighboring FCs. These findings demonstrate that epithelial-derived NPPs can perform complex phagocytic tasks typically attributed to professional phagocytes such as macrophages. Our work establishes the Drosophila ovary as a robust in vivo system to uncover conserved and novel aspects of epithelial plasticity and phagocytic function, particularly those involving transient behaviors missed by fixed-sample analyses.
    DOI:  https://doi.org/10.64898/2026.05.21.726826
  7. Curr Top Dev Biol. 2026 ;pii: S0070-2153(26)00041-4. [Epub ahead of print]169 193-235
    Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.
    Jeremy R Egbert.
      The cell cycle of the mammalian oocyte arrests in prophase around the time of birth and remains in meiotic arrest as it grows interdependently with increasing layers of surrounding somatic cells as a structure called an ovarian follicle. Within preovulatory follicles, gap junction communication between somatic cells and the oocyte allow cyclic nucleotides to maintain equilibrium concentrations that prevent premature meiotic resumption. Intercellular communication is also required for the mid-cycle surge in luteinizing hormone to alter cyclic nucleotide dynamics and cause the oocyte cell cycle to resume. In this review, the increasingly well-understood mechanisms by which meiotic arrest and meiotic resumption occur will be summarized, along with recent developments made possible by an improved cyclic nucleotide sensor and imaging techniques. These studies have uncovered new aspects of this process and helped clarify the required role of epidermal growth factor receptor signaling in meiotic resumption. Growing evidence that the cyclic nucleotide-associated participants in oocyte cell cycle regulation, first described in rodents, appear to be universal across mammals will also be summarized. This understanding has fostered new approaches to assisted reproductive technologies (ARTs) in domesticated animals and humans.
    Keywords:  Functional syncytium; Gap junction; Guanylyl cyclase; Intercellular signaling; Live imaging; Meiotic arrest; Meiotic resumption; Ovarian follicle; Regulatory phosphorylation
    DOI:  https://doi.org/10.1016/bs.ctdb.2026.04.008
  8. Curr Top Dev Biol. 2026 ;pii: S0070-2153(26)00040-2. [Epub ahead of print]169 97-136
    Building a resilient ovarian reserve: Early soma-oocyte interactions.
    Cora Thompson, Alaina Houghton-Chamberlain, Joan S Jorgensen.
      Soma-oocyte interactions are a key component in female fertility. First the ovary must adopt a female fate and become populated with supporting somatic cells. We discuss the origins of each somatic cell type with a particular focus on pre-granulosa cell origins and differentiation. Upon germ cell arrival into the ovary, the oogonia develop into cysts and begin their interactions with neighboring pre-granulosa cells. Cell to cell contacts change over time as the germline cysts form and then break down to facilitate primordial follicle formation. These changes do not happen in isolation, rather, they are mediated by signaling cascades and changes in the physical structures. The processes and developmental changes explored in this chapter are crucial for the longevity and success of the primordial follicle and thus, an essential part of female fertility.
    Keywords:  Balbiani body; Development; Follicle; Germline cyst; Meiosis; Mitosis; Oocyte; Ovary; Pre-granulosa cell
    DOI:  https://doi.org/10.1016/bs.ctdb.2026.04.007
  9. Curr Top Dev Biol. 2026 ;pii: S0070-2153(26)00035-9. [Epub ahead of print]169 137-167
    Activation of primordial follicles.
    In-Won Lee, Deepak Adhikari.
      Primordial follicle activation represents the pivotal and rate-limiting transition that governs the size and longevity of the ovarian reserve, thereby shaping female reproductive lifespan. Although the vast majority of primordial follicles remain quiescent, a small fraction is periodically activated through tightly regulated signaling events. Emerging evidence reveals that dormancy is not a passive state, but an actively maintained program orchestrated by intrinsic oocyte pathways, surrounding pre-granulosa cells, and the ovarian microenvironment. Key intracellular regulator PI3K-Akt-FOXO3 signaling establishes the oocyte's threshold for activation, and pre-granulosa cell cues, including KITL-KIT interactions, mechanical constraints, and extracellular matrix dynamics, modulate this core signaling. Additionally, paracrine signals from stromal cells, local hypoxia, and biomechanical forces contribute to the spatial patterning of activation within the ovary. Integration of these inputs ensures both the lifelong preservation of a dormant pool and the continuous supply of follicles entering the growth phase. Recent advances in single-cell technologies, imaging, and lineage tracing systems have begun to redefine the temporal and spatial complexity of primordial follicle activation. Dysregulation of this system underlies a spectrum of reproductive disorders, from premature ovarian insufficiency to diminished ovarian reserve and aberrant follicle recruitment. Understanding the molecular logic of activation not only illuminates the biology of ovarian aging but also informs emerging therapeutic strategies, including targeted modulation of signaling pathways, ovarian tissue engineering, and fertility preservation interventions. This chapter describes current knowledge of the mechanisms governing primordial follicle activation and highlights key gaps that will shape future research in ovarian biology.
    Keywords:  Female fertility; Follicle activation; Oocyte; Ovarian reserve; Pre-granulosa cells; Primordial follicles; Signaling pathways
    DOI:  https://doi.org/10.1016/bs.ctdb.2026.04.002
  10. Development. 2026 Jun 01. pii: dev205295. [Epub ahead of print]153(11):
    The SPN-4 Rbfox RNA-binding protein selects maternal mRNAs for CCR4-NOT-dependent clearance in early Caenorhabditis elegans embryos.
    Caroline A Spike, Dylan M Parker, Tatsuya Tsukamoto, Naly Torres Mangual, Erika C Tsukamoto, Karissa Coleman, Micah D Gearhart, David Greenstein, Erin Osborne Nishimura.
      The elimination of maternal mRNAs is an essential feature of the maternal-to-zygotic transition. We report an essential pathway that clears many maternal transcripts from early C. elegans embryos using the Rbfox-related SPN-4 RNA-binding protein as a specificity factor and the CCR4-NOT deadenylase complex as an effector. We biochemically identified SPN-4-associated mRNAs from late-stage oocytes and found that the set of SPN-4-associated transcripts is enriched for maternal mRNAs that undergo early decay. Single-molecule fluorescence in situ hybridization experiments established that many SPN-4-associated mRNAs fail to be eliminated in the absence of SPN-4. In the 3'UTRs of two target mRNAs, we identified Rbfox motifs that are required for SPN-4-dependent clearance in vivo and bind SPN-4 in vitro. In a genetic screen to identify factors that work with SPN-4, we isolated mutant alleles of CCR4-NOT components. Auxin-induced degradation of the LET-711/NOT1 scaffold and the CCF-1 deadenylase disrupted clearance of two SPN-4-associated transcripts. Our results support a model in which SPN-4 initiates expression in late-stage oocytes, associates with maternal mRNA targets through RNA sequences in their 3'UTRs and promotes CCR4-NOT-mediated decay during early embryogenesis.
    Keywords:   C. elegans ; lin-41 and chs-1; CCR4-NOT deadenylase complex; Maternal mRNA clearance; Oocyte-to-embryo transition; SPN-4
    DOI:  https://doi.org/10.1242/dev.205295
  11. J Reprod Dev. 2026 May 31.
    ​​Deletion of Ybx1 results in germ cell hypoplasia in mouse embryos.
    Shinya Ikeda, Yayoi Obata, Yusuke Sotomaru.
      Several evolutionarily conserved genes have been reported to be involved in gametogenesis. Y-box binding proteins, which have a conserved nucleotide-binding cold-shock domain, have been reported in both vertebrates and invertebrates. Although homologues of Ybx1 in Drosophila and zebrafish play important roles in oogenesis, the involvement of mouse Ybx1 in gametogenesis or gonadal development remains unclear. In this study, we investigated the female and male fetal gonadal phenotypes in Ybx1 knockout mice. Embryos of Ybx1 knockout mice at E13.5 showed slender gonads compared to those of the controls. Whole-mount gonadal immunostaining revealed a significant decrease in the number of female embryonic germ cells. Immunocytochemistry revealed that YB-1, a protein encoded by Ybx1, is expressed in both germ and gonadal somatic cells. In contrast, transcriptome analysis of germ cells and gonadal somatic cells at E13.5 revealed that deletion of Ybx1 did not cause global changes in gene expression. However, Anapc5 and Rpn1, which have been implicated in germ cell survival, were significantly downregulated in Ybx1(-/-) female germ cells. Furthermore, Acta2 and Mmp2, known Ybx1-regulated genes, were also significantly downregulated in Ybx1(-/-) female gonadal somatic cells, potentially contributing to germ cell hypoplasia. Collectively, our results suggest that YB-1 may have a role in gonadal development by promoting germ cell survival and gonadal development.
    Keywords:  Fetal germ cells; Germ cell hypoplasia; Oogenesis
    DOI:  https://doi.org/10.1262/jrd.2026-025
  12. Curr Top Dev Biol. 2026 ;pii: S0070-2153(26)00042-6. [Epub ahead of print]169 169-191
    Mechanisms of germ-soma communication during follicular growth.
    Claude Robert, Ricardo Perecin Nociti.
      Communication between cells is essential for orchestrating tissue, organ, and whole-body cohesion. The communication can occur within the same cell (autocrine signaling), between neighboring cells (paracrine signaling), from distant cells (endocrine signaling), and between adjacent cells (juxtacrine signaling). Extracellular vesicle secretions, where messaging molecules like proteins, RNAs, and lipids are embedded in a membrane-enclosed particle released by the signaling cell, allow signaling to occur upon uptake and release of the cargo. Intercellular communications in synchrony between folliculogenesis and oogenesis involve both long-distance and short-distance messaging within the ovarian follicle, which is segmented into different cell types, with the oocyte lying at the center. Cells can generate extensions to increase the range of messaging by reaching out to more distant cells the so-called protrusion-based intercellular communication exemplified by tunneling nanotubes (TNTs), MT-nanotubes (MTNTs), microvilli, filopodia, and cytonemes. In mammalian oocytes, the filopodia from follicular cells that grow towards the oocyte is known as transzonal projections (TZPs). They accumulate large cargos, such as EVs, proteins and RNAs, at the tip creating the gametic synapses. These projections keep the oocyte and follicular cells connected and exchanging cytoplasmic content despite the apparent physical separation caused by the oocyte's zona pellucida. The protective and nurturing nature of follicular cells towards the oocyte, due to the presence of cellular interconnectivity within follicular cells and the oocyte, is conserved between species and is essential for communication, playing a crucial role in the development of a high-quality oocyte.
    Keywords:  Filopodia; Intercellular communications; Oocyte; Ovarian follicle; Tran szonal projections
    DOI:  https://doi.org/10.1016/bs.ctdb.2026.04.009
  13. Curr Top Dev Biol. 2026 ;pii: S0070-2153(26)00038-4. [Epub ahead of print]169 237-272
    The ovarian stroma as a key regulator of follicular development and gamete quality across the reproductive lifespan.
    Shweta S Dipali, Francesca E Duncan.
      The follicle is the functional unit of the ovary and has been the historical focus of ovarian biology research. However, recently a greater emphasis has been placed on the role of the ovarian microenvironment, or stroma, in supporting the follicle and germ cell within. The ovarian stroma is composed of the ovarian surface epithelium, blood and lymphatic vasculature, nerves, immune cells, fibroblasts, mesenchymal cells, and the extracellular matrix (ECM). The stroma provides structural, biomechanical, biochemical, and metabolic support for follicle activation and development, in turn impacting gamete quality. The ovary is one of the first organs to age characterized by a loss of gamete quantity and quality. In addition, the stroma exhibits significant age-related changes - becoming fibrotic, inflammatory, and stiff. This review summarizes the physiological functions of ovarian stromal cell populations and components in supporting ovarian function, alterations in the ovarian stroma that occur with advanced age, and the resulting reproductive consequences.
    Keywords:  Aging; Epithelium; Extracellular matrix; Fibroblasts; Immune cells; Nerves; Ovarian stroma; Ovary; Vasculature
    DOI:  https://doi.org/10.1016/bs.ctdb.2026.04.005
  14. bioRxiv. 2026 May 19. pii: 2026.05.19.726329. [Epub ahead of print]
    In the Drosophila germline H2Av and Arp6 suppress transposons by driving piRNA pathway expression.
    Norbert Andrási, Hannah M Ryon, Yicheng Luo, Katalin Fejes Tóth.
      The spatiotemporal control of transcription and the maintenance of germline genome integrity depend on dynamic chromatin architecture. In Drosophila , the actin-related protein Arp6-a core subunit of the SWR1-like Domino chromatin remodeling complex-mediates the deposition of the histone variant H2Av. Previous studies have established H2Av as a key transcriptional regulator that modulates the +1 nucleosome barrier to promote RNA Polymerase II (Pol II) pause release and productive elongation. Conversely, H2Av is also integral to heterochromatin assembly and gene silencing. Here we demonstrate that Arp6 and H2Av are essential for female fertility and the global repression of transposable elements (TEs) in the Drosophila ovary. Rather than repressing TEs directly, we show that Arp6 and H2Av maintain genomic stability indirectly by driving the transcription of core PIWI-interacting RNA (piRNA) pathway genes. Depletion of either chromatin factor leads to a significant loss of piRNAs and reduced non-canonical transcription of dual-strand piRNA clusters. This defect stems from a failure to express the Rhino-Deadlock-Cutoff (RDC) complex, alongside the downregulation of multiple other piRNA biogenesis factors. Genomic profiling confirms that H2Av acts predominantly as an activating signal at host gene promoters. Upon H2Av or Arp6 depletion, genes that rely on H2Av for their expression exhibit a distinct upstream shift and more precise spatial localization of the Pol II peak at the TSS, indicating an impaired transition from transcription initiation into productive elongation. Together, our findings build upon the known transcriptional activation functions of the Arp6-H2Av axis, revealing that this established chromatin mechanism is critical for licensing piRNA-mediated genome defense and ensuring germline maintenance.
    DOI:  https://doi.org/10.64898/2026.05.19.726329
  15. Curr Top Dev Biol. 2026 ;pii: S0070-2153(26)00039-6. [Epub ahead of print]169 273-305
    Impact of cancer immunotherapies on oocyte health and ovarian function.
    Yasmin Lewis, Yujie Cao, Jordan Higgins, Lauren R Alesi, Amy L Winship, Karla J Hutt.
      The ovary is an immunologically active organ in which tightly regulated interactions between immune cells, cytokines, and reproductive hormones are essential for follicle and oocyte development, ovulation, luteal function, and maintenance of the ovarian reserve. Immune checkpoints such as PD-1, PD-L1, and CTLA-4 are increasingly recognized as key regulators of immune tolerance beyond classical lymphoid tissues, yet their roles within the ovary remain poorly defined. Immune checkpoint inhibitors (ICIs), which target these pathways to enhance anti-tumor immunity, have transformed cancer treatment and are increasingly administered to women of reproductive age. While traditional cancer therapies are well known to compromise ovarian function and fertility, the reproductive consequences of ICIs are only beginning to emerge. Here we synthesize current knowledge of ovarian immune biology, with a focus on T cells and immune checkpoint signaling, and integrate clinical, preclinical, and mechanistic evidence linking immune checkpoint blockade to ovarian dysfunction. We discuss immune-related adverse events (irAEs), their management, and emerging evidence that the ovary may be uniquely sensitive to immune checkpoint perturbation. Collectively, this review highlights emerging knowledge of T cells and immune checkpoints in the ovary, highlights critical gaps in our understanding of immune - ovarian crosstalk, and discusses the urgent need to define the reproductive risks of ICIs to inform fertility preservation strategies and clinical decision-making for women with cancer.
    Keywords:  Cancer; Fertility; Immune cells; Immune checkpoints; Ovary
    DOI:  https://doi.org/10.1016/bs.ctdb.2026.04.006
  16. bioRxiv. 2026 May 20. pii: 2026.05.19.726147. [Epub ahead of print]
    Developmentally programmed changes in cytoplasmic mechanics revealed by active microrheology in C. elegans embryos.
    Saaya Koizumi, Ayama Tokuyasu, Akinori W M Miyamoto, Takayuki Torisawa, Hirokazu Tanimoto, Akatsuki Kimura.
      Cytoplasmic mechanical properties are often treated as constant background parameters, yet whether they change systematically during development remains unclear. Here, we directly measured cytoplasmic mechanics during early embryogenesis of Caenorhabditis elegans by establishing active microrheology using micrometer-sized magnetic droplets. Active microrheology revealed a progressive decrease in creep compliance from the 1-cell to the 8-cell stage, indicating a progressive stiffening of the local cytoplasmic environment during development. This decrease persisted even when cytokinesis was inhibited, demonstrating that it cannot be explained solely by geometric changes associated with cell division. Passive microrheology using 40-nm fluorescent beads showed a consistent decrease in probe mobility over development. Together, these results demonstrate that cytoplasmic mechanical properties undergo a gradual, developmentally programmed change during embryogenesis that cannot be explained by cell division-associated geometry alone.
    DOI:  https://doi.org/10.64898/2026.05.19.726147
  17. bioRxiv. 2026 May 25. pii: 2026.05.21.726840. [Epub ahead of print]
    Conditional replacement of the mouse LH receptor with GFP, enabling imaging of cell migration during ovulation.
    Corie M Owen, Katie M Lowther, Deborah Kaback, Laurinda A Jaffe, Siu-Pok Yee.
      To facilitate the investigation of signaling by the luteinizing hormone receptor (LHR), we created a mouse line called Lhr -COIN. This line allows for the conditional replacement of the Lhr coding sequence with enhanced green fluorescent protein (eGFP), resulting in both a conditional knockout line and a reporter line. By breeding these mice with mice expressing Cre recombinase, we generated mice in which either one or both Lhr alleles were replaced with eGFP. Notably, mice in which one Lhr allele in the granulosa cells was replaced with eGFP exhibited normal LH responsiveness. This enabled live imaging of LH-induced migration of LH-receptor-expressing granulosa cells within preovulatory ovarian follicles. The Lhr -COIN mouse line holds significant potential for future research on LHR function and localization in the ovary and other tissues.
    DOI:  https://doi.org/10.64898/2026.05.21.726840
  18. Nat Cell Biol. 2026 Jun 01.
    Segmental specification of the human female fetal reproductive tract revealed by spatiotemporal dynamics.
    Zuoxi He, Qian Wang, Lisha Ding, Yisi Wang, Hongcheng He, Wuyue Han, Siyao Li, Jing Fu, Can Luo, Jingyu Li, Rui Gao, Yueyue Chen, Ling Mei, Dongmei Wei, Jian Meng, Yueting Zhang, Tao Wang, Xiaoyu Niu.
      The proper development of the human female reproductive tract (FRT) is essential for reproductive competence. However, the mechanisms underlying its segmental specialization remain underexplored. This gap limits our knowledge of congenital anomalies and adult reproductive disorders. Herein, we build a spatiotemporal transcriptomic atlas of the distinct human FRT segments development from gestational week (GW) 10 to 25, capturing cellular composition and lineage dynamics. We discovered that the upper and lower segments of FRT are composed of distinct mesenchymal and epithelial cell subpopulations starting from as early as GW10. Mesenchymal lineages in different segments arise from distinct mesenchymal stem cell (MSC)-like cells and undergo critical differentiation between GW13 and GW22, giving rise to fibroblasts and smooth muscle cells. TGF-β and PDGF signalling pathways seem to play a pivotal role in guiding these distinct fate transitions. Concurrently, epithelial development exhibits region-specific trajectories: upper and lower FRT epithelial cells originate from different stem-like populations and undergo key transitions between GW14 and GW22. Specifically, we identify MSC-like1 and MSC-like2 as regulatory populations that may influence epithelial differentiation via WNT5A-FZD and IGF1-IGF1R signalling pathways in the upper and lower FRT, respectively. This finding highlights a spatially specific mesenchymal-epithelial crosstalk that shapes regional epithelial identity. Altogether, our work provides a comprehensive insight into the segmental specification and coordinated lineage decisions that offer foundational resource for understanding FRT development, congenital anomalies and tissue engineering.
    DOI:  https://doi.org/10.1038/s41556-026-01962-4
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