bims-ovagas Biomed News
on Ovarian aging and cGAS
Issue of 2026–05–17
nine papers selected by
Haiyuan Mu, University of California Berkeley
  1. Ovarian aging: maintenance and activation of the primordial follicle pool.
  2. A fragmented field: why ovarian biology needs dedicated integrative platforms.
  3. The Spatiotemporal Proteome Landscape of Aging: Structural determinants of age-sensitive proteome remodeling.
  4. Protocol for ex vivo culture of neonate mouse ovaries to study early follicle activation.
  5. Molecular mechanisms and multi-organ regulatory roles of anti-Müllerian hormone in female reproduction.
  6. The Interplay of Aging and the Immune System.
  7. ∂Voltage-gated calcium channel activity of gonadotropin-releasing hormone (GnRH) neurons is altered by age and by prenatal androgen exposure in female mice.
  8. Whole ovary cryopreservation and transplantation: a narrative review of technological advances, biological hurdles, and clinical translation in fertility preservation.
  9. Assessment of Survival and Expansion of Mouse Pre-Antral Follicles in 3D System Within Hyaluronic Acid-Alginate Hydrogel Cocultured With Human Theca Stem and Progenitor Cells.
  1. J Ovarian Res. 2026 May 11.
    Ovarian aging: maintenance and activation of the primordial follicle pool.
    Qian Wang, Guodong Zhao, Jiaqi Zhou.
      As the earliest aging organ in females, the ovary undergoes functional decline and structural senescence that drive reproductive system alterations. Central to this process is the primordial follicle-the non-renewable reserve of female germ cells and the sole source for oocyte development. The primordial follicle pool is established prenatally, fixed in quantity, and cannot regenerate after birth, serving as the fundamental biological reserve that determines both fertility potential and reproductive lifespan. Once depletion begins, it is irreversible, directly limiting the reproductive window and influencing ovarian endocrine function. Therefore, this review briefly summarizes the latest research progress on primordial follicle development, providing an in-depth analysis of primordial follicle dormancy and activation mechanisms as well as therapeutic approaches for associated complications. This work holds significant implications for understanding reproductive aging, preventing and treating reproductive endocrine disorders, and developing novel fertility strategies, offering valuable references for comprehending the biological mechanisms and potential applications of primordial follicles.
    Keywords:  Activation; Maintenance; Metabolism; Ovarian aging; Primordial follicle
    DOI:  https://doi.org/10.1186/s13048-026-02116-8
  2. Biol Reprod. 2026 May 14. pii: ioag100. [Epub ahead of print]
    A fragmented field: why ovarian biology needs dedicated integrative platforms.
    Christiani A Amorim, Suzannah A Williams, Stine Gry Kristensen.
      The ovary plays a central role in female reproductive and endocrine health, yet ovarian biology remains structurally fragmented across disciplines including reproductive medicine, endocrinology, toxicology, and bioengineering. This fragmentation limits the integration of mechanistic insights, slows clinical translation, and constrains our understanding of the ovary as a complex, multi-scale organ. Recent advances in technologies such as single-cell analysis, organoid systems, and biomaterials have generated unprecedented knowledge, but these developments often remain siloed. Here, we argue that advancing the field requires the establishment of dedicated integrative platforms that bridge basic, translational, and clinical research. Using recent interdisciplinary initiatives as a proof-of-concept, we propose key principles for such platforms and call for structural changes in how ovarian research is organized, supported, and disseminated.
    Keywords:  Interdisciplinarity; ovarian biology; research infrastructure; scientific integration; systems biology; translational research
    DOI:  https://doi.org/10.1093/biolre/ioag100
  3. bioRxiv. 2026 Mar 01. pii: 2026.02.26.708310. [Epub ahead of print]
    The Spatiotemporal Proteome Landscape of Aging: Structural determinants of age-sensitive proteome remodeling.
    Seungmin Yoo, Lingraj Vannur, Liying Li, Christopher Young, Qingqing Liu, Zhihui T Wen, Ying Zhang, Laurence Florens, Kausik Si, Junming Zhuang, Fan Zheng, Chuankai Zhou.
      Aging is marked by a decline in cellular functions accompanied by widespread changes in mRNA and protein abundance, yet whether aging broadly remodels subcellular protein localization and concentration-and why some proteins change while others remain stable-remains unclear. This gap matters because cellular function depends not only on expression levels but also on correct spatial organization. Using yeast replicative aging as a model, we built a robotic pipeline to enrich old cells from 5,661 strains, acquired 90 million single-cell 3D images, and applied machine learning to map proteome-wide changes in localization, concentration, and aggregation throughout aging. This age-resolved single-cell atlas uncovers widespread proteome remodeling and rewiring of protein interaction networks. Moreover, structural analysis reveals biophysical determinants of age-sensitive proteome remodeling across ages and species. Together, these results reveal a structure-encoded intrinsic principle underlying spatial proteome breakdown during aging and provide a resource to dissect mechanistic links among aging hallmarks.
    DOI:  https://doi.org/10.64898/2026.02.26.708310
  4. STAR Protoc. 2026 May 08. pii: S2666-1667(26)00192-9. [Epub ahead of print]7(2): 104539
    Protocol for ex vivo culture of neonate mouse ovaries to study early follicle activation.
    Julie Feld Madsen, Stine Bundgaard Birkebæk, Karin Lykke-Hartmann.
      Establishing an ex vivo culture of neonatal ovaries enables controlled investigation of early follicle dynamics. Here, we present a protocol for isolating ovaries from neonatal female mice for maintaining intact ovarian architecture by ex vivo culture on a membrane allowing access to defined medium. We describe procedures for media preparation, ovary dissection, culture setup, and follicle development by stereomicroscopy and histological assessment. This protocol provides a platform for examining the regulation of the primordial-to-primary transition and growth. For complete details on the use and execution of this protocol, please refer to Amoushahi et al.1.
    Keywords:  Cell Biology; Cell culture; Developmental biology; Model Organisms; Molecular Biology
    DOI:  https://doi.org/10.1016/j.xpro.2026.104539
  5. Commun Biol. 2026 May 14. pii: 658. [Epub ahead of print]9(1):
    Molecular mechanisms and multi-organ regulatory roles of anti-Müllerian hormone in female reproduction.
    Jiahao Li, Wenjun Zhu, Yonghui Bu, Li Li, Hengxi Wei, Shouquan Zhang.
      Anti-Müllerian hormone (AMH), produced by ovarian granulosa cells, is a key regulator of female reproduction. Traditionally seen as a local follicular brake, emerging evidence calls for a paradigm shift. We propose that AMH acts as a context-dependent signaling hub. It primarily signals via the Smad1/5/8 pathway and interacts with Wnt/β-catenin and MAPK cascades to regulate follicle growth and steroidogenesis. Beyond the ovary, AMH and its receptors are expressed in the hypothalamus, pituitary, uterus, and placenta, modulating the hypothalamic-pituitary-gonadal axis and other reproductive processes. This review provides a comprehensive framework for understanding AMH as a context-dependent signaling hub in female mammals.
    DOI:  https://doi.org/10.1038/s42003-026-10273-1
  6. Mo Med. 2026 Mar-Apr;123(2):123(2): 116-123
    The Interplay of Aging and the Immune System.
    Rajeev Aurora, Brittani Lubeck, Aarushi Choudhari.
      Aging is a genetically regulated biological process. We review recent studies that highlight the role of the immune system, specifically chronic inflammation, in contributing to age-related decline and frailty. Of clinical importance, aging is a risk factor for multiple conditions. During childbearing years, women are largely protected from diseases associated with aging. However, menopause, which marks the loss of ovarian function, introduces a significant shift. An unexpected and remarkable discovery is that the decline in estrogen levels triggers chronic inflammation, which in turn promotes atherosclerosis, osteoporosis, and cognitive decline. Gaining a deeper understanding of the crosstalk between aging and the immune system is essential for advancing strategies that support healthy aging.
    Keywords:  Aging; biological age; immunity; inflammation
  7. bioRxiv. 2026 Feb 27. pii: 2026.02.25.707515. [Epub ahead of print]
    ∂Voltage-gated calcium channel activity of gonadotropin-releasing hormone (GnRH) neurons is altered by age and by prenatal androgen exposure in female mice.
    Xi Chen, Jennifer Jaime, R Anthony DeFazio, Suzanne M Moenter.
      Polycystic ovary syndrome (PCOS), a common cause of infertility, is marked by persistently high luteinizing hormone (LH)-pulse frequency, presumably driven by high-frequency GnRH pulses. Prenatally androgenized (PNA) mice mimic neuroendocrine PCOS symptoms including high LH-pulse frequency. GnRH neurons from adult PNA mice have a higher firing rate than those from vehicle (VEH) mice; this is reversed in prepubertal mice despite more excitatory inputs at both ages. We hypothesized voltage-gated Ca 2+ currents (I Ca ) help set intrinsic excitability of GnRH neurons and are altered by development and/or PNA treatment. Whole-cell patch-clamp recordings were used to measure GnRH neuron I Ca in 3wk-old and adult VEH and PNA mice. PNA treatment increased I Ca density and depolarized the I Ca -half inactivation potential at both ages. In VEH but not PNA mice, the Ca 2+ -half activation potential was depolarized in adults versus 3wks. Age decreased the inactivation rate of a fast I Ca regardless of PNA treatment. GnRH neuron firing rate during current injections was higher at 3wks than in adulthood in VEH mice only. Blocking small-conductance Ca²⁺-activated K⁺ current with apamin increased GnRH neuron firing rate except in adult PNA mice. Apamin changed the post-spike-train membrane response from hyperpolarization to depolarization; during development, this net effect of apamin became smaller in PNA mice. In summary, while GnRH neurons from PNA mice have increased I Ca , they lack some developmental changes in I Ca kinetics and intrinsic excitability observed in VEH mice. Ca²⁺-activated K⁺ currents are less prominent in GnRH neurons from adult PNA mice, perhaps contributing to increased spontaneous firing.
    Significance statement: Hyperactivation of GnRH neurons, which control reproductive endocrine function, can lead to increased LH-pulse frequency and is a hallmark of hyperandrogenemia polycystic ovary syndrome (PCOS). We used a mouse model of prenatal androgenization (PNA) that recapitulates the neuroendocrine aspects of PCOS to test the role of calcium currents (I Ca ) in the PNA phenotype and the typical pubertal process. PNA treatment increased I Ca in GnRH neurons both before and after puberty. Calcium plays a crucial role in neurosecretion thus this may enhance GnRH release. Another role of calcium is activation of calcium-sensitive potassium currents, which tend to decrease action potential firing rate. Despite increased I Ca, calcium-activated potassium currents are less effective in adult PNA mice, perhaps contributing to GnRH neuron hyperactivation.
    DOI:  https://doi.org/10.64898/2026.02.25.707515
  8. J Assist Reprod Genet. 2026 May 15.
    Whole ovary cryopreservation and transplantation: a narrative review of technological advances, biological hurdles, and clinical translation in fertility preservation.
    Chen Chen, Xianying Lu, Jianye Wang, Ping Zhou, Chenyue Zhang, Yulong Mu, Qun Gao.
      Significant advances in cancer therapies have improved survival but often cause premature ovarian failure. While ovarian tissue cryopreservation (OTC) is an option, it suffers from ischemic damage. Whole ovary cryopreservation and transplantation (WOCT) presents a pioneering alternative. By preserving the ovary with its vascular pedicle, WOCT enables direct microvascular anastomosis during transplantation, allowing immediate blood flow. This key advantage aims to drastically reduce follicular loss and restore both fertility and long-term hormonal function through a single procedure. This review synthesizes the current state of WOCT. It outlines the structural challenges of cryopreserving a large, whole organ, critically evaluates slow freezing versus vitrification techniques, and details the surgical complexities of transplantation. Major postoperative challenges like thrombosis and follicular depletion are emphasized. The potential of adjunctive therapies (e.g., stem cells) to enhance outcomes is discussed. The review also addresses unique barriers to clinical translation, including oncological safety and the procedure's irreversibility. Finally, it explores the promise of emerging technologies like nanoparticle-assisted rewarming. The future of WOCT depends on multidisciplinary collaboration and standardized protocols to transition it from experiment to an established clinical option for restoring comprehensive ovarian function.
    Keywords:  Fertility preservation; Ischemia–reperfusion injury; Nanotechnology; Organoid; Ovarian transplantation; Stem cell therapy; Whole ovary cryopreservation
    DOI:  https://doi.org/10.1007/s10815-026-03894-2
  9. Mol Reprod Dev. 2026 05;93(5): e70108
    Assessment of Survival and Expansion of Mouse Pre-Antral Follicles in 3D System Within Hyaluronic Acid-Alginate Hydrogel Cocultured With Human Theca Stem and Progenitor Cells.
    Leila Badban, Reihaneh Pirjani, Mojtaba Rezazadeh Valojerdi.
      Cancer treatments can impair fertility in young women, and existing fertility preservation methods are often unsuitable for prepubertal patients. Replicating the natural follicular microenvironment in a three-dimensional (3D) in vitro culture of ovarian follicles presents a promising alternative, and co-culturing follicles with ovarian cells may enhance oocyte development. This study used a 3D culture system of hyaluronic acid and alginate to grow mouse preantral follicles and human theca stem and progenitor cells (hTSCs and hTPCs). Ovarian tissue was obtained from five transsexual women; hTSCs were isolated, expanded, confirmed, and differentiated into hTPCs. Preantral mouse follicles were collected and co-cultured with hTSCs and hTPCs in 0.5% hyaluronic acid-alginate (HA-Alg) hydrogel for 14 days. hTSCs were identified by spindle-shaped fibroblast morphology, positive alkaline phosphatase activity, expressing mesenchymal markers like CD29, CD44, and CD90, and differentiation potential to adipocytes and osteocytes-like cells. hTSCs differentiation into hTPCs causes an increase in steroidogenic gene expression, hormone release, and follicular recruitment. Coculturing of mouse preantral follicles with hTSCs and hTPCs in HA-Alg hydrogel induced follicle survival, hormone release, and oocyte maturation. Human theca cells in the stem and progenitor cells stage may support mouse follicle growth, survival, and steroidogenesis.
    Keywords:  Theca cells; hyaluronic acid; ovarian follicles; stem cells
    DOI:  https://doi.org/10.1002/mrd.70108
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