bims-ovagas Biomed News
on Ovarian aging and cGAS
Issue of 2026–07–12
eight papers selected by
Haiyuan Mu, University of California Berkeley
  1. The Explosion of Life: Lessons from Live Imaging of Ovulation.
  2. Full-length transcriptomic profiling reveals age-associated isoform remodeling and altered coding potential in the mouse ovary.
  3. A Three-Dimensional Culture Model Supporting Human Secondary-to-Antral Follicle Development In Vitro.
  4. Mammalian aging involves genome-wide splicing degeneration leading to functional decline.
  5. Decoding stage-specific functions of PRC2 in early embryogenesis uncovers roles in preimplantation development and primordial germ cell fate.
  6. Single-cell Transcriptomic Atlas of Ovarian Endometriosis Patient's Follicular Fluid: Unraveling Novel Insights into Abnormal Follicular Development.
  7. Lab-grown sperm: scientists inch closer to fertility breakthrough.
  8. TGF-β drives the conversion of conventional NK cells into uterine tissue-resident NK cells to support murine pregnancy.
  1. Reproduction. 2026 Jul 08. pii: xaag085. [Epub ahead of print]
    The Explosion of Life: Lessons from Live Imaging of Ovulation.
    Anita Bichisecchi, Petra Mikec, Christopher Thomas.
      Ovulation is the process by which an egg is released from an ovarian follicle, ready for fertilisation. It is a multi-scale transformation that converts endocrine cues into coordinated tissue and extracellular matrix remodelling, culminating in physical rupture of the follicle wall. Live imaging has reshaped understanding by replacing static snapshots with direct observation of sequence and timing. Here, we outline the architecture of the preovulatory follicle and the LH-driven signalling programmes that coordinate cumulus expansion, oocyte maturation, tissue remodelling and rupture. We then chart key imaging milestones-from early time-lapse of exteriorised ovaries, to clinical endoscopy in humans, perfused ovary preparations, intravital multiphoton microscopy, and ex vivo live imaging of isolated follicles. Finally, we summarise emerging approaches to probe physical regulation, including intrafollicular pressure measurements and complementary methods to quantify tissue and matrix mechanics. Together, these advances show that ovulation is a staged programme that demands quantitative, time-resolved measurements.
    Keywords:  Ovulation; ex vivo follicle culture; live imaging; oocyte; ovary
    DOI:  https://doi.org/10.1093/reprod/xaag085
  2. J Ovarian Res. 2026 Jul 08.
    Full-length transcriptomic profiling reveals age-associated isoform remodeling and altered coding potential in the mouse ovary.
    Haiyang Wu, Xiaoyu Yin, Min Zhang, Kanghua Zhong, Yalin Liang, Yiduo Wang, Yelian Yan, Xueqi Dong, Yuxin Xu, Hao Yu, Keliang Wu, Shenli Yuan, Chuanxin Zhang.
      Ovarian aging, marked by a progressive diminution of oocyte quality and quantity, is a major contributor to declining female fertility and age-related reproductive disorders. However, transcript-level changes underlying this process remain incompletely understood. In this study, we applied Oxford Nanopore long-read RNA sequencing to profile full-length transcripts from granulosa cells and oocytes of young (6-8 weeks) and aged (10 months) mice, complemented by Illumina short-read sequencing for orthogonal support. We performed transcript annotation, differential expression analysis, alternative polyadenylation (APA) analysis, and weighted gene co-expression network analysis (WGCNA) to investigate age-associated transcriptomic changes. Comprehensive annotation classified 130,730 high-confidence transcripts, including over 100,000 putative novel isoforms, and revealed that aging was associated with a shift toward isoforms with lower predicted coding potential. Exploratory enrichment analysis suggested that transcripts with lower predicted coding potential were associated with biological processes such as protein synthesis and chromosome segregation. APA analysis identified age-associated 3'UTR shortening. Transcript-level differential expression and isoform-switching analysis uncovered 795 significant switching events across both cell types, frequently associated with predicted open reading frame changes and potential protein-domain loss. Exploratory WGCNA highlighted modules associated with aging and cell-type specificity, including an Esr1-derived hub transcript, TALONT000180938, from a gene previously linked to ovarian function and disease. Many disease-associated genes exhibited cell-type-specific isoform usage, with several novel isoforms undetectable at the gene level. Our results indicate that long-read sequencing improves isoform-level resolution of ovarian transcriptomic diversity and identifies candidate aging-associated transcript alterations that may be relevant to reproductive decline.
    Keywords:  Full-length transcriptome; Isoform switching; Ovarian aging
    DOI:  https://doi.org/10.1186/s13048-026-02193-9
  3. J Vis Exp. 2026 Jun 16.
    A Three-Dimensional Culture Model Supporting Human Secondary-to-Antral Follicle Development In Vitro.
    Jianfei Gong, Zhiyun Zhu, Jinze Yang, Jian Han, Mengyuan Tian, Tianren Wang, Haiyan Wang, Huanmin Wang, Jie Yan, Jie Qiao.
      Human ovarian folliculogenesis is a complex, tightly regulated process that is challenging to study directly in vivo. Although in vitro models are essential for mechanistic research, existing systems remain suboptimal because they cannot recapitulate the spatiotemporal dynamics of follicle development. This study presents a 3D culture model that supports human follicle development from the secondary to the antral stage. This model successfully recapitulates key in vivo morphological events, including sustained follicular growth, a distinct diameter expansion phase from day 10, and antral cavity formation around day 20. Importantly, this developmental progression culminated in the successful retrieval of viable oocytes at the germinal vesicle (GV) stage. Furthermore, immunofluorescence analysis revealed distinct expression patterns of gonadotropin receptors in somatic cells, consistent with granulosa and theca cell identity. Inner granulosa-like cells exhibited high follicle-stimulating hormone receptor (FSHR), whereas outer theca-like cells showed high luteinizing hormone receptor (LHR) expression. This model offers a valuable platform for studying human folliculogenesis and reproductive toxicology and provides a reference for optimizing in vitro follicle culture systems for secondary-to-antral stage development.
    DOI:  https://doi.org/10.3791/70713
  4. bioRxiv. 2026 Jun 29. pii: 2026.06.26.734787. [Epub ahead of print]
    Mammalian aging involves genome-wide splicing degeneration leading to functional decline.
    Sirui Zhang, Alexander Tyshkovskiy, Kejun Ying, Siqi Wang, Vadim N Gladyshev.
      Alternative splicing exhibits significant changes during development and aging, affecting the composition and variance in the transcriptome. However, it is unclear whether and how age-associated splicing dysregulation leads to functional consequences. Here, an integrative analysis of transcriptome data across mouse and human tissues revealed that aging is characterized by systematic deterioration of the fidelity of RNA splicing, here termed splicing degeneration, a measure of functional alteration of reading frame and domain configuration of protein products. Genes with higher aging-associated splicing degeneration were more conserved and enriched for processes such as RNA metabolism and antigen presentation. By assessing alternative splicing events associated with functional deterioration, we quantified the degree of splicing degeneration. Its level increased with age but was alleviated following calorie restriction or rapamycin treatment, indicating that it can serve as a new molecular hallmark of aging. Mechanistically, through a comprehensive meta-data analysis, we discovered that splicing degeneration is associated with age-associated changes in specific splicing factors, which in turn showed a strong association with age-related transcriptome changes. Overall, our study demonstrates the intricate relationship between aging and genome-wide splicing degeneration, revealing a promising target for aging interventions acting to reverse splicing degeneration.
    DOI:  https://doi.org/10.64898/2026.06.26.734787
  5. Nat Cell Biol. 2026 Jul 10.
    Decoding stage-specific functions of PRC2 in early embryogenesis uncovers roles in preimplantation development and primordial germ cell fate.
    Chengjie Zhou, Meng Wang, Zhiyuan Chen, Yi Zhang.
      Early embryogenesis is accompanied by dynamic epigenetic modifications. Although such dynamics are important in cell intrinsic regulation of gene expression, their extrinsic roles in mediating intercellular communication during early embryogenesis are less understood. Here, using the dTAG system, we reveal previously underappreciated stage-specific functions of PRC2 in regulating preimplantation and primordial germ cell (PGC) development. We demonstrate that PRC2 plays important roles in regulating maternal-to-zygotic transition and epiblast formation. By systematically analysing H3K27me3 and H3K4me3 dynamics, we redefine the timing of bivalency establishment and uncover a stepwise mechanism governing bivalency acquisition in early embryogenesis. Moreover, PRC2 regulates proper PGC numbers in the epiblast by controlling Esrrb expression in the extraembryonic ectoderm. Thus, our study uncovers a previously unknown cell-autonomous function of PRC2 in preimplantation development and its non-cell-autonomous impact in PGC number regulation, both through interplays between epigenetic-epigenetic and epigenetic-transcription factors networks.
    DOI:  https://doi.org/10.1038/s41556-026-02002-x
  6. Reproduction. 2026 Jul 07. pii: xaag083. [Epub ahead of print]
    Single-cell Transcriptomic Atlas of Ovarian Endometriosis Patient's Follicular Fluid: Unraveling Novel Insights into Abnormal Follicular Development.
    Meng Zhang, Xinye Hu, Haiyan Lin, Yang Gang, Xiaohui Ji, Yaoqiu Wu, Chunwei Cao, Yabin Guo, Qingxue Zhang.
      Ovarian endometrioma (OMA), an endometriosis subtype, involves hemorrhagic cysts formed by ectopic endometrial-like tissue, causing pelvic pain, inflammation, and infertility by disrupting ovarian function. Despite its impact, the single-cell dynamics in OMA follicular fluid are poorly understood. We performed scRNA-seq (10x Genomics) on follicular fluid from a patient's affected (2793 cells) and unaffected (4699 cells; control) ovaries. Analysis revealed four cell types, including a novel TCR+ macrophage subtype. Affected-side granulosa cells showed abnormal developmental trajectories linked to dysregulated steroid pathways. Immune cells exhibited heightened inflammation and reduced macrophage phagocytosis. Cell-cell communication highlighted prominent MIF and MK signaling from granulosa cells. This study provides the first single-cell transcriptomic profile of OMA follicular fluid, elucidating aberrant granulosa cell development, immune dysregulation, and distinctive cellular interactions, enhancing understanding of OMA's impact on follicular development and suggesting potential diagnostic/therapeutic targets.
    Keywords:  Cellular Profiling; Follicular Fluid; Immune Microenvironment; Ovarian Endometriosis; Single-Cell RNA Sequencing
    DOI:  https://doi.org/10.1093/reprod/xaag083
  7. Nature. 2026 Jul 10.
    Lab-grown sperm: scientists inch closer to fertility breakthrough.
    Heidi Ledford.
      
    Keywords:  Cell biology; Developmental biology; Medical research
    DOI:  https://doi.org/10.1038/d41586-026-02172-6
  8. Elife. 2026 07 08. pii: RP109878. [Epub ahead of print]15
    TGF-β drives the conversion of conventional NK cells into uterine tissue-resident NK cells to support murine pregnancy.
    Josselyn D Barahona, Liping Yang, D Michael Nelson, Wayne M Yokoyama.
      Tissue microenvironments shape lymphocyte differentiation to align immune function with local physiological demands. Uterine natural killer (NK) cells are critical for reproductive success, yet the molecular cues in the uterus that instruct their specialized identities remain incompletely understood. Here, we identify a TGF-β-dependent differentiation pathway by which circulating conventional NK cells convert into uterine tissue-resident NK cells during murine pregnancy. Loss of TGF-β receptor II expression in Ncr1-expressing cells disrupted this conversion, markedly reducing tissue-resident NK cells in the gravid uterus. Impaired TGF-β-driven uterine tissue-resident NK cell differentiation during murine pregnancy led to abnormal spiral artery remodeling and increased fetal resorption rates at mid-gestation, ultimately reducing litter sizes at birth. Collectively, these findings define TGF-β as a pivotal driver of tissue-resident NK cell differentiation in the gravid uterus and establish a mechanistic framework through which the uterine microenvironment programs NK cell identity to meet the physiological demands of gestation.
    Keywords:  TGF-β; immunology; inflammation; mouse; natural killer cells; pregnancy
    DOI:  https://doi.org/10.7554/eLife.109878
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