bims-ovagas Biomed News
on Ovarian aging and cGAS
Issue of 2026–05–24
seven papers selected by
Haiyuan Mu, University of California Berkeley
  1. An agent-based model suggests how senescent cell behavior and matrix mechanics drive pulmonary fibrosis in aged mice.
  2. Rewiring the inflammatory microenvironment to reverse ovarian failure: Immunomodulatory implications of finerenone.
  3. Whole Mount Immunostaining of Fetal and Neonatal Mouse Ovaries.
  4. Conventional IVF in the horse past, present, and future: physiological and technical insights.
  5. 20S proteasome-regulated proteostasis in ELVAs is critical for oocyte-to-embryo transition and female fertility.
  6. Surging towards a better understanding of ovulation.
  7. Dissecting the transcriptomic signature of porcine oocyte during primordial follicle formation from single cell resolution.
  1. bioRxiv. 2026 May 06. pii: 2026.05.01.722023. [Epub ahead of print]
    An agent-based model suggests how senescent cell behavior and matrix mechanics drive pulmonary fibrosis in aged mice.
    Mackenzie L Skelton, Julie Leonard-Duke, Leilani R Astrab, Joshua A Goedert, Riley T Hannan, Shayn M Peirce, Jeffrey M Sturek, Steven R Caliari.
      Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease of aging, driven by dysregulated fibroblast activation and accompanied by collagen accumulation in the lung interstitium, resulting in tissue stiffening. While the accumulation of senescent cells has been increasingly implicated in IPF pathogenesis, understanding the reciprocal dynamics of senescent fibroblast levels and evolving tissue mechanics is difficult to achieve with experimental approaches alone. To address this limitation, we developed an agent-based model (ABM) of fibroblast activation in the lung that couples cell behavior to the dynamic mechanical changes accompanying fibrosis. This model was parameterized entirely from experimental data in young mice to enable robust validation and then adapted to fit aged mouse biology for additional validation. Both young and aged models accurately reflected changes in collagen accumulation and stiffness burden of experimental systems. We then incorporated senescent cell behavior into the aged model to investigate how senescent cell burden influences fibrosis progression and how cell-cell interactions drive senescent cell accumulation. These simulations identified a unique role for juxtacrine-mediated contact between non-senescent and senescent fibroblasts in expanding the total senescent cell burden. Our ABM also revealed that the timing of immune-mediated senescent cell clearance critically regulates fibrotic outcomes. Together, this ABM provides useful insights into how the interrelated dynamics of tissue mechanics and senescent fibroblasts drive fibrosis progression.
    DOI:  https://doi.org/10.64898/2026.05.01.722023
  2. J Reprod Immunol. 2026 May 15. pii: S0165-0378(26)00084-7. [Epub ahead of print]175 104915
    Rewiring the inflammatory microenvironment to reverse ovarian failure: Immunomodulatory implications of finerenone.
    Kuan-Hao Tsui, Chia-Jung Li.
      Recent evidence suggests that the nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone restores folliculogenesis and fertility in premature ovarian insufficiency (POI) by reversing ovarian stromal fibrosis. While structural remodeling of the extracellular matrix (ECM) is a primary finding, this editorial highlights that chronic low-grade inflammation and immune dysregulation are fundamental drivers of fibrotic progression. We propose that the therapeutic success of finerenone reflects a critical "rewiring" of the inflammatory microenvironment. MR signaling in immune cells, such as macrophages and T lymphocytes, promotes proinflammatory phenotypes and the secretion of profibrotic mediators including TGF-β, IL-6, and TNF-α. By antagonizing MR, finerenone interrupts the self-reinforcing immune-fibrotic feedback loop, facilitating immunological recalibration toward a reparative state. This perspective positions the immune-fibrotic axis as a rational therapeutic target alongside traditional ECM remodeling. Future translational priorities should include detailed immune profiling and the integration of inflammatory biomarkers to refine clinical strategies. Ultimately, recognizing the inseparability of fibrosis and chronic inflammation will be essential for developing effective interventions to rescue organ function in POI and other inflammation-driven pathologies.
    Keywords:  Finerenone; Immunomodulation; Ovarian fibrosis; Premature ovarian insufficiency
    DOI:  https://doi.org/10.1016/j.jri.2026.104915
  3. J Vis Exp. 2026 Apr 28.
    Whole Mount Immunostaining of Fetal and Neonatal Mouse Ovaries.
    Melissa E Pepling, Kirsten Rasmussen, Jaelyn Anderson, Lauren Erickson.
      The ovarian reserve consists of the oocytes available to a female for reproduction and are found in primordial follicles, each containing one oocyte surrounded by several granulosa cells. The oocytes start out as primordial germ cells that form outside the gonad and migrate to the developing ovary during embryonic development. Once they reach the ovary, they become oogonia and divide by mitosis, with incomplete cytokinesis, forming clusters of interconnected cells called germ cell cysts. While in cysts, the cells enter meiosis and become oocytes. In the mouse, two days before birth, the cysts begin to break apart, and each oocyte is packaged into a primordial follicle. Only some of the oocytes survive during this process, the rest undergo apoptosis. The regulation of cyst breakdown and primordial follicle formation is only partially understood, and identifying the molecules involved is crucial to understanding this process. Whole mount immunostaining of developing mouse ovaries can be used to determine the localization of potential regulatory molecules and to assess effects on primordial follicle formation due to mutation or other molecular changes using oocyte and somatic cell markers. Ovaries are harvested from fetal or neonatal mice, fixed in formaldehyde, and blocked. The ovaries are then exposed to antibodies against a protein of interest, followed by secondary antibodies conjugated to a fluorescent tag that detect the primary antibodies. Finally, the ovaries are mounted and examined by confocal microscopy. This procedure can detect multiple proteins of interest and can be applied to other small tissues, such as fetal mouse testes.
    DOI:  https://doi.org/10.3791/69455
  4. J Equine Vet Sci. 2026 May 18. pii: S0737-0806(26)00173-5. [Epub ahead of print] 105938
    Conventional IVF in the horse past, present, and future: physiological and technical insights.
    K Hinrichs.
      For decades, conventional in vitro fertilization (IVF) in the horse was ineffective, leading to reliance on intracytoplasmic sperm injection (ICSI) for both research and clinical in vitro embryo production. However, the ability to achieve IVF is essential to the study of key reproductive processes, including sperm capacitation, fertilization, and early embryonic development. Recently we have established a repeatable and efficient IVF system for horses, using long-term (9-22 h) sperm pre-incubation. For clinical use, IVF has many features that may support higher embryo quality than does ICSI, and so may increase the rate of foal production per recovered oocyte. While unlikely to replace ICSI for use with semen of poor quality or limited availability, IVF may eventually provide a clinical alternative to ICSI for normospermic stallions. Work is needed to increase the robustness of the current technique for semen from different sources, to streamline the procedures, and to shorten the time required for capacitation.
    Keywords:  Embryo; Fertilization; ICSI; IVF; Oocyte
    DOI:  https://doi.org/10.1016/j.jevs.2026.105938
  5. EMBO J. 2026 May 21.
    20S proteasome-regulated proteostasis in ELVAs is critical for oocyte-to-embryo transition and female fertility.
    Yan Rong, Yingyan Chen, Huiwen Cao, Chengkan Liu, Haomang Xu, Xiaomei Tong, Anxuan Fang, Leilei Ai, Yucong Zhu, Yingyi Zhang, Peipei Ren, Xiaoxuan Li, Yufan Gao, Xiaolin Tian, Lugeng He, Songying Zhang, Chao Yu.
      Programmed degradation of maternal proteins is essential for the oocyte-to-embryo transition (OET). While pharmacological inhibition studies have established the importance of proteasomes in ovarian reserve maintenance, oocyte maturation and fertilization, the physiological impact of intrinsic proteasome insufficiency and underlying molecular mechanisms remain poorly understood. In mice, endolysosomal vesicular assemblies (ELVAs), specialized membraneless compartments composed of proteasomes, endolysosomes and autophagosomes, facilitate protein degradation during oocyte maturation and early embryogenesis. In this study, we generated mice with oocyte-specific deletion of the proteasomal core subunit Psma7, to investigate the physiological function of the 20S proteasome and its roles in ELVAs-mediated protein degradation. PSMA7-deficiency destabilized 20S proteasomes and disrupted translocation of ELVAs, leading to pronounced accumulation of ubiquitinated proteins in oocytes and zygotes. Consequently, maternal Psma7 deletion resulted in female infertility, manifested by impaired oocyte maturation and developmental arrest at one- to two-cell stage. Furthermore, we observed reduced proteasome abundance and dysfunction of ELVAs in aged oocytes, providing a mechanistic explanation for the decline in developmental competence associated with oocyte aging. Taken together, our findings elucidate the critical function of proteasome-regulated proteostasis within ELVAs in maintaining oocyte quality during OET and reproductive aging.
    DOI:  https://doi.org/10.1038/s44318-026-00813-0
  6. Elife. 2026 May 18. pii: e111681. [Epub ahead of print]15
    Surging towards a better understanding of ovulation.
    Lillian Rose, Alexander S Kauffman.
      The ability to record the real-time activity of specialized neurons in the brains of female mice is providing new insights into the hormonal control of ovulation.
    Keywords:  GnRH; LH surge; estrogen; fertility; kisspeptin; mouse; neuroendocrinology; neuroscience; photometry
    DOI:  https://doi.org/10.7554/eLife.111681
  7. J Ovarian Res. 2026 May 21.
    Dissecting the transcriptomic signature of porcine oocyte during primordial follicle formation from single cell resolution.
    Xin-Hao Zhang, Kai Zhang, Yu Tian, Gui-Li Ruan, Fa-Li Zhang, Ke-Xin Zhu, Ai-Ying Li, Wei Shen, Jun-Jie Wang.
       BACKGROUND: Ovarian reserve, refers to the number of primordial follicle (PF) in mammals, is a decisive factor affecting the reproductive lifespan of females. However, the molecular mechanism of PF formation has not been fully elucidated, especially in large mammals. In the study, the ovarian tissues at embryonic day 95 (E95) and postnatal day 0 (PD0) were collected for single-nucleus transcriptome sequencing, attempting to investigate the transcriptome dynamic of porcine oocyte during PF formation at a single-cell level.
    RESULTS: In the results, we identified in detail three germ cell clusters with different transcriptional modes. Moreover, through a comparative analysis of developmental trajectory in pig, mouse and monkey, several conserved regulatory genes that associated with the developmental fate of germ cells were identified. By employing SCENIC software, we identified 27 transcription factors specific to developmental stages of germ cells. In addition, a protein interaction network between transcription factors and conserved genes was constructed and it discovered a key transcription factor, enhancer of zeste homolog 2 (EZH2), which is expressed exclusively in oocytes during PF formation, and there is the asynchrony of its expression in germ cells between the medulla and cortex regions. Further, during the in vitro culture of mouse ovaries, the inhibition of EZH2 expression significantly decreased the number of oocytes and leading to the decline of protein expressions that essential for PF formation.
    CONCLUSIONS: This study provides a single-cell map of pig ovary in the late embryonic development and newly born periods, and enriches the public understanding of primordial follicle formation in mammals.
    Keywords:  EZH2; Ovarian; Pig; Primordial follicle; Single-cell transcriptomics
    DOI:  https://doi.org/10.1186/s13048-026-02126-6
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