bims-ovagas Biomed News
on Ovarian aging and cGAS
Issue of 2026–06–14
seven papers selected by
Haiyuan Mu, University of California Berkeley
  1. Developmental and functional landscape of theca cells in ovarian biology.
  2. The post-reproductive ovary shifts from a reproductive to an immune-like organ.
  3. Defining functional puberty in female C57BL/6J mice using endocrine, cytological and morphological markers.
  4. Neuroendocrine Regulation of Female Fertility: The Role of CNS-Derived Hormones.
  5. Genome integrity checkpoints in mammalian oogenesis.
  6. Proteomics-based insights into mammalian oocyte and early embryo development.
  7. Protection and deprotection of the Rec8 cohesin complex during meiosis.
  1. Biol Res. 2026 Jun 08.
    Developmental and functional landscape of theca cells in ovarian biology.
    Mahnaz Haddadi, Samane Adib, Christiani A Amorim, Azam Dalman, Mojtaba Rezazadeh Valojerdi.
      Ovarian theca cells constitute essential components of the follicular microenvironment and play central roles in follicular development, steroidogenesis, and endocrine regulation. Despite their significance, the developmental origins, differentiation processes, and functional dynamics of theca cells remain incompletely defined, particularly in humans. This review provides an updated synthesis of current knowledge on the ontogeny, molecular signaling pathways, and intercellular interactions of theca cells. It also presents recent findings on the role of theca stem or progenitor cells and their relevance to reproductive disorders, including polycystic ovary syndrome (PCOS), hyperthecosis, and ovarian insufficiency. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science through May 2025. Search terms included "theca cells," "theca progenitors," "follicular development," "ovarian differentiation," "steroidogenesis," and "reproductive disorders." Original research articles and reviews providing mechanistic insights were included. Current evidence indicates that several signaling pathways, including IGF, SCF, FGF, members of the TGF-β superfamily, GDF9, BMPs, and Hedgehog proteins, are involved in the recruitment, proliferation, and differentiation of theca cells. Bidirectional communication among oocytes, granulosa cells, and theca cells remains essential for folliculogenesis. Increasing evidence links theca cell dysfunction to the pathophysiology of PCOS, primary ovarian insufficiency, and reproductive aging. The identification of theca stem cells (TSCs) and their proposed roles in ovarian regeneration represents an important conceptual advance. A deeper understanding of theca cell biology may guide the development of targeted strategies for infertility and ovarian dysfunction. In contrast, the integration of TSC biology offers new directions for reproductive medicine and reproductive health.
    Keywords:  Follicular development; Ovarian theca cells; Reproductive endocrinology; Steroidogenesis; Theca cell differentiation; Theca progenitor cells
    DOI:  https://doi.org/10.1186/s40659-026-00680-3
  2. Mol Hum Reprod. 2026 Jun 10. pii: gaag038. [Epub ahead of print]
    The post-reproductive ovary shifts from a reproductive to an immune-like organ.
    Aubrey Converse, Shweta S Dipali, Ian P Schowe, Emmett B Kelly, Shivani S Jambunathan, Sarah R Ocañas, Michael B Stout, Michele T Pritchard, Francesca E Duncan.
      Reproductive aging in females is characterized by the irreversible depletion of ovarian follicles, yet the structure and function of the post-reproductive ovary remain poorly defined. Using paired histological and bulk transcriptomic analyses of ovaries from reproductively young (2 m), reproductively old (18 m), and post-reproductive (24 m) mice, we mapped how ovarian identity evolves beyond follicle exhaustion. As expected, follicle loss, stromal remodeling, and increased collagen deposition were observed in the reproductively old and post-reproductive cohorts. Transcriptomic analyses revealed a shift from reproductive functionality to an immune-dominant signature with age. Correspondingly, post-reproductive ovaries exhibited increased infiltration of T cells, macrophages, and multinucleated giant cells. Although old and post-reproductive ovaries diverged substantially from young ovaries, they also showed discrete transcriptomic differences, indicating that the ovary continues to undergo molecular changes after reproductive senescence. Lastly, age-dependent changes in ovarian factors that are predicted to be secreted suggest that the post-reproductive ovary could be a source of pro-inflammatory signaling mediators with the potential to modulate extra-ovarian tissues. These findings challenge the assumption that the post-reproductive ovary is inert, instead indicating that it acquires an immune identity with potential endocrine and paracrine influence on whole-body aging.
    Keywords:  Menopause; fibrosis; inflammation; oopause; ovarian aging; ovary; post-reproductive; stroma
    DOI:  https://doi.org/10.1093/molehr/gaag038
  3. Sci Rep. 2026 Jun 12.
    Defining functional puberty in female C57BL/6J mice using endocrine, cytological and morphological markers.
    Mélanie Chester, Noalig Wyckens, Eloïse Airaud, Raphaël Corre, Claire-Hélène Petrovic, Alice Pierre, Céline Julie Guigon.
      Puberty marks the transition to reproductive competence and is driven by activation of the hypothalamo/pituitary/gonadal axis, culminating in first ovulation in females. In mice, puberty onset is commonly inferred from vaginal opening and estrous cyclicity, but the precise timing of first ovulation remains unclear. Here, we aimed to define reliable parameters of functional puberty in female C57BL/6J mice by integrating external, endocrine, and morphological measures. Vaginal opening and daily vaginal cytology were combined with daily serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements and ovarian histology using the Pubertal Ovarian Maturation Score (Pub-Score), which estimates ovulation based on follicular development and corpus luteum morphology. Notably, we observed substantial inter-individual variability in puberty-related events, and no link between estrous cytology and first ovulation. Pub-Score analysis indicated that first ovulation occurred between 36 and 54 days postnatal, with a mean around 44 days, with no correlation with vaginal cytology. LH surges were detected in some of the females that had ovulated and showed limited temporal correspondence with vaginal cytology or Pub-Score estimates. Together, these findings demonstrate that puberty in female mice is a gradual, asynchronous process and that external or cytological markers alone are insufficient to define functional reproductive maturity.
    Keywords:  Estrous cycle; LH surge; Ovulation; Pub-Score; Puberty
    DOI:  https://doi.org/10.1038/s41598-026-57314-7
  4. J Mol Endocrinol. 2026 Jun 11. pii: JME-25-0049. [Epub ahead of print]
    Neuroendocrine Regulation of Female Fertility: The Role of CNS-Derived Hormones.
    Amirreza Shakoeizadeh, Erfan Shahabinejad, Mahdi Heydari, Amirmohammad Shahidzadeh, Soheila Pourmasumi.
      Infertility is an increasing concern for many women and can affect both physical and emotional well-being. The central nervous system (CNS) -particularly the hypothalamus, pituitary gland, and pineal gland - plays a crucial role in female reproductive health. We conducted a narrative review of relevant studies published between 2015 and 2025, sourcing data from PubMed and Scopus. Our goal was to investigate how dysregulation of hormones from the hypothalamus, pituitary gland, and pineal gland contributes to fertility-related disorders, such as impairments in ovulation, oocyte quality, and embryo development. Both human and significant animal studies were considered to better understand how CNS hormones affect fertility. The findings emphasize the roles of key hormones, including gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), melatonin, Adrenocorticotropic Hormone (ACTH), Thyroid-Stimulating Hormone (TSH), and vasopressin (ADH). The proper timing and balance of these hormones are vital. For instance, GnRH pulses regulate the release of LH and FSH, which are essential for ovulation and follicle development. Melatonin supports oocyte health and helps maintain the menstrual cycle, while ACTH and TSH are also involved in reproductive function. Vasopressin contributes by affecting uterine activity and hormone production. Understanding these hormonal interactions may lead to better diagnostic tools and more effective treatment strategies for conditions such as polycystic ovary syndrome (PCOS) and other fertility-related disorders. Unlike previous studies, this research provides a comprehensive investigation of how CNS-mediated hormonal regulation influences female reproductive outcomes, examining the roles of all involved hormones.
    Keywords:  Brain Glands; Female Fertility; Hormone; Neuroendocrine
    DOI:  https://doi.org/10.1530/JME-25-0049
  5. Biol Reprod. 2026 Jun 11. pii: ioag118. [Epub ahead of print]
    Genome integrity checkpoints in mammalian oogenesis.
    John C Schimenti.
      Preserving chromosome integrity and minimizing mutations are crucial in the germline to prevent infertility, pregnancy loss and birth defects. This is particularly important in mammalian females, who reach puberty with a limited pool of oocytes and therefore have a finite reproductive lifespan. The most complex and genome-threatening stage of oogenesis is meiosis, during which homologous chromosomes pair and segregate at the first meiotic division. This process depends on the formation of hundreds of genetically programmed double-strand breaks (DSBs), which promote homologous recombination repair (HRR) and thereby drive homolog pairing and synapsis. Genetic studies in model organisms have revealed the existence of quality control mechanisms, or checkpoints, that detect unrepaired DNA damage or defective synapsis and, in mammals, eliminate defective oocytes from the ovarian reserve. After nearly three decades of study, a model has emerged in which the DNA damage and synapsis checkpoints share extensive mechanistic overlap. Several DNA repair proteins and damage sensors have been co-opted to recognize unsynapsed chromatin and transmit these signals through canonical DNA damage response pathways to well-known downstream effectors including TRP53 (p53) and TAp63 that trigger oocyte death. This review summarizes the key studies that have defined genetic quality control mechanisms that act before and during oogenesis, underscoring their relevance to infertility and reproductive aging.
    DOI:  https://doi.org/10.1093/biolre/ioag118
  6. Nat Cell Biol. 2026 Jun 11.
    Proteomics-based insights into mammalian oocyte and early embryo development.
    Sifan Rong, Zhuocheng Liu, Wencheng Zhu, Liangshan Mu.
      Advances in proteomics are transforming our understanding of mammalian oocyte maturation and preimplantation embryo development. These resources and their findings provide unprecedented insights into the molecular underpinnings of developmental competence. Here we summarize the ongoing development of proteomic methodologies and highlight the stage-specific reprogramming events of the proteome in both humans and mice, underscoring the unique utility of proteomics in deciphering oocyte maturation and early embryonic development. Furthermore, we discuss the clinical implications of these findings, highlighting the translational potential of proteomics in understanding reproductive ageing, improving oocyte quality, and refining the outcomes of assisted reproductive technology.
    DOI:  https://doi.org/10.1038/s41556-026-01993-x
  7. Cell Rep. 2026 Jun 11. pii: S2211-1247(26)00619-4. [Epub ahead of print]45(6): 117541
    Protection and deprotection of the Rec8 cohesin complex during meiosis.
    Yongxin Liu, Ke Zhang, Ziteng Bai, Li Sun, Haitong Hou, Yoshinori Watanabe.
      During meiosis I, the cohesin Rec8 is cleaved by separase along the chromosome arms but is protected at the centromere by shugoshin (Sgo1); during meiosis II, it is not protected. In fission yeast, another meiotic regulator, meikin (Moa1), supports the protective function of Sgo1 primarily by phosphorylating Rec8 at S450. Here we show that both meiosis I-specific proteins, Sgo1 and Moa1, are degraded during anaphase I by the APC/C-Slp1 pathway. To explore the possibility of ectopic protection during meiosis II, we expressed non-degradable forms of Moa1 and Sgo1 during meiosis. Our analyses revealed that stabilization of the Sgo1 protein and phosphorylation of Rec8 at S449 and S450 are necessary and sufficient for the protection of Rec8 cohesin during meiosis II. Furthermore, our results suggest that the phosphorylation-dependent interaction between Rec8 and Sgo1 during meiosis is prominent at mono-oriented kinetochores but not at bi-oriented kinetochores.
    Keywords:  CP: cell biology; MPS1; PLK1; Rec8 cohesin; deprotection of cohesin; meikin; meiosis; protection of cohesin; shugoshin
    DOI:  https://doi.org/10.1016/j.celrep.2026.117541
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