bims-ovagas Biomed News
on Ovarian aging and cGAS
Issue of 2026–05–03
eight papers selected by
Haiyuan Mu, University of California Berkeley
  1. Estrogen Receptor Alpha and Beta Chromatin Interactions Govern Ovarian Folliculogenesis but Dissipate During Ovulation.
  2. Developing anti-Müllerian hormone as an ovarian reserve biomarker.
  3. Competition between separated parental genomes in fertilized eggs aids development.
  4. Multimodal data analysis reveals asynchronous aging dynamics across female reproductive organs.
  5. Molecular basis of chromosome segregation and age-associated errors in oocyte meiosis I.
  6. Uridine restores oocyte quality and mitigates female reproductive aging by inhibition of ferroptosis in mice.
  7. Beware of your "oocyte specific" Cre line: somatic cell Cre expression in several Zp3-Cre lines and the Gdf9-iCre transgenic line†.
  8. The stromal microenvironment of ovary: a novel area in polycystic ovary syndrome.
  1. Endocrinology. 2026 Apr 30. pii: bqag052. [Epub ahead of print]
    Estrogen Receptor Alpha and Beta Chromatin Interactions Govern Ovarian Folliculogenesis but Dissipate During Ovulation.
    Doan T Dinh, Timothy R McPhee, Natalie J Foot, Rebecca L Robker, Darryl L Russell.
      Estrogen signalling plays an important role in normal ovarian functions, including follicle development, ovulation and ovarian cell identity maintenance. Estrogen acts through the estrogen receptors alpha (ERα) and beta (ERβ), both of which are involved in ovarian gene regulation. However, the molecular mechanisms that lead to shared and unique receptor actions in the ovary remain poorly understood. Additionally, co-regulators that contribute to estrogen receptor actions in the ovary have remained unexplored. Here, we distinguished the roles of ERα and ERβ at different ovarian stages through characterising the chromatin binding profile of each receptor in granulosa cells during pre- or peri-ovulation. We found that ERα/β genomic action was prominent during follicle development prior to ovulation. Loss of ERα/β binding after LH-stimulus was associated with the downregulation of folliculogenesis genes, while ERα/β binding contributed little to the activation of genes that are required for ovulation. ERα and ERβ showed highly similar chromatin binding patterns in granulosa cells. Through motif enrichment analysis and integration of other ovarian transcription factor cistromes, we identified potential interactors of ERα and ERβ, including a very strong overlap in chromatin binding with androgen receptor (AR) in pre-ovulatory follicles. These findings demonstrate ERα and ERβ to have highly conserved chromatin interaction functions including interaction with AR to mediate gene expression during folliculogenesis.
    Keywords:  cistrome; estrogen receptor; granulosa cell; ovary
    DOI:  https://doi.org/10.1210/endocr/bqag052
  2. Mol Hum Reprod. 2026 Apr 11. pii: gaag021. [Epub ahead of print]32(2):
    Developing anti-Müllerian hormone as an ovarian reserve biomarker.
    Bart C J M Fauser.
      The first anti-Müllerian hormone (AMH) radioimmunoassay became available for clinical use in the early 2000s. This MHR Legacy Series review discusses key contributions from our own group towards establishing AMH as a robust ovarian reserve biomarker. Initial studies in female volunteers demonstrated decreasing serum AMH concentrations with increasing female age, along with a direct correlation between AMH levels and the number of antral follicles. The most relevant clinical conditions where measurements of serum AMH appear to be of great value include the diagnosis of various forms of ovarian dysfunction, especially polycystic ovary syndrome and premature ovarian insufficiency. In addition, a close correlation between initial serum AMH levels and ovarian response to standard stimulation for IVF has been firmly established, resulting in the development of a safe and effective AMH-based algorithm for individualized ovarian stimulation. Another area, beyond our own research, where AMH serum measurements have proven to be of great clinical significance is oncofertility. The capacity of AMH levels to predict fecundity-either spontaneous or following infertility treatment-or forecast age of menopause later in life remains uncertain and needs more well-designed, prospective, follow-up studies.
    Keywords:  IVF; anti-Müllerian hormone; fecundity; follicle; ovary; polycystic ovary syndrome; pregnancy; premature ovarian insufficiency
    DOI:  https://doi.org/10.1093/molehr/gaag021
  3. Nature. 2026 Apr 29.
    Competition between separated parental genomes in fertilized eggs aids development.
      
    Keywords:  Cell biology; Developmental biology
    DOI:  https://doi.org/10.1038/d41586-026-01270-9
  4. Nat Aging. 2026 Apr 29.
    Multimodal data analysis reveals asynchronous aging dynamics across female reproductive organs.
    Oleksandra Soldatkina, Laura Ventura-San Pedro, Natàlia Pujol-Gualdo, Allal El Hommad, Jose Miguel Ramirez, Aida Ripoll-Cladellas, Maria Sopena-Rios, Daniel Tabares, Miguel Ángel Pérez-Elena, David Torrents, Jaume Ordi, Marta Melé.
      Female reproductive aging has systemic health implications, yet tissue-level dynamics remain poorly understood. Here we integrate deep learning analysis of 1,112 histology images with RNA sequencing from 659 samples across seven female reproductive organs in donors aged 20-70 years. We uncover asynchronous trajectories: the ovary ages gradually, whereas the uterus shows an abrupt molecular and morphological shift around menopause. This uterine transition is independently supported by plasma proteomics data from a large population cohort, indicating that organ-linked aging signatures are detectable in circulation. Tissue segmentation highlights the myometrium as strongly age affected, with extracellular matrix remodeling and immune activation. Epithelial tissues also show coordinated age-related remodeling, with a sharp menopausal transition in the vaginal epithelium. Multi-omics factor analysis links these histological changes to nonlinear gene-expression shifts enriched for reproductive traits, including pelvic organ prolapse and age at menarche. Together, these findings establish menopause as a key inflection point in female aging and provide a tissue-resolved, multi-dataset framework for late-life health.
    DOI:  https://doi.org/10.1038/s43587-026-01098-y
  5. Biol Reprod. 2026 Apr 25. pii: ioag086. [Epub ahead of print]
    Molecular basis of chromosome segregation and age-associated errors in oocyte meiosis I.
    Tomoya S Kitajima.
      Oocyte meiosis determines chromosomes that are transmitted from the mother to the next generation. The molecular mechanisms underlying meiotic chromosome segregation are organized in distinct chromosomal regions-the core centromere, peri-centromere, and chromosome arms. A common molecular basis for mechanisms operating in these distinct regions is Rec8 cohesin, together with cooperating regulatory pathways. This Review describes Rec8-cohesin-based mechanisms operating in each chromosomal region and discusses how these mechanisms work coordinately to achieve chromosome segregation during meiosis I, focusing primarily on insights from studies using mouse oocytes as a model system. Based on this molecular understanding, it further discusses how age-associated decline of chromosomal Rec8 cohesin can lead to chromosome segregation errors, a major cause of infertility, miscarriage, and congenital disorders.
    DOI:  https://doi.org/10.1093/biolre/ioag086
  6. Nat Commun. 2026 Apr 29.
    Uridine restores oocyte quality and mitigates female reproductive aging by inhibition of ferroptosis in mice.
    Jingyue Chen, Jianing Shen, Dongxu Li, Guangjun Huang, Rui Wang, Xiaofan Sun, Meijie Chen, Tianyi Liao, Liying Yan, Peng Yuan, Bo Xiong, Jie Qiao.
      Advanced maternal age is a key factor in female infertility, primarily due to declines in ovarian reserve and oocyte quality. However, the metabolic mechanisms underlying reproductive aging remain unclear. Here, we show that uridine levels in the plasma and ovaries of aged mice are significantly reduced compared with young controls. Building on this, we find that uridine supplementation significantly improves meiotic maturation, fertilization, and early embryonic development of aged oocytes, both in vivo and in vitro. Further microtranscriptomic analyses reveal that uridine enhances oocyte quality by inhibiting ferroptosis and enhancing mitochondrial function. Moreover, by integrating Limited Proteolysis-Small Molecule Mapping, western blotting and siRNA-based functional assays, we identify that uridine binds to poly(rC)-binding protein 1, thereby suppressing ferroptosis and preserving mitochondrial function. Collectively, these findings demonstrate that uridine supplementation improves fertility in aged female mice and provide mechanistic insight into ferroptosis in oocyte aging.
    DOI:  https://doi.org/10.1038/s41467-026-72406-8
  7. Biol Reprod. 2026 Apr 30. pii: ioag093. [Epub ahead of print]
    Beware of your "oocyte specific" Cre line: somatic cell Cre expression in several Zp3-Cre lines and the Gdf9-iCre transgenic line†.
    Paula Stein, Chihiro Emori, Elizabeth Padilla-Banks, Lenka Radonova, Artiom Gruzdev, Masahito Ikawa, Carmen J Williams.
      Several zona pellucida 3 (Zp3)-Cre driver mouse lines are used to enable conditional loss-of-function studies in oocytes. The Knowles Zp3-Cre line, currently maintained live at the Jackson Laboratory, is the most widely published. We recently found that the transgene expressed in the Knowles line contains a truncated metallothionein (Mt1) sequence that is expressed at high levels in oocytes from transgenic mice. This finding led us to search for an alternative Zp3-Cre line that did not express an exogenous Mt1 transcript. We tested a second transgenic Zp3-Cre line and then created our own transgenic Zp3-Cre line, neither of which was oocyte-specific as documented by crossing to the tdTomato reporter line. Similar testing confirmed the exquisite oocyte specificity of the Knowles Zp3-Cre line. An alternative to Zp3-Cre is to use the Gdf9-iCre line, which is reported to be oocyte-specific and expressed beginning at the primordial follicle stage. This line similarly showed high somatic tissue Cre expression. Reasoning that a knock-in approach would ensure oocyte specificity, we used a CRISPR/Cas9 approach to insert Cre into the endogenous Zp3 locus. However, crosses of this knock-in line with tdTomato females revealed high somatic tissue expression. Both the Zp3-Cre knock-in and Gdf9-iCre alleles, when paternally inherited, induced Cre expression by the blastocyst stage, explaining the broad tissue distribution. We conclude that the Knowles Zp3-Cre transgenic line remains the best model for generating oocyte-specific expression, though investigators should be aware of the spurious Mt1 expression from the transgene.
    Keywords:  Gdf9-iCre; Oocyte; Zp3-cre; conditional knockout; transgenic
    DOI:  https://doi.org/10.1093/biolre/ioag093
  8. J Ovarian Res. 2026 Apr 27.
    The stromal microenvironment of ovary: a novel area in polycystic ovary syndrome.
    Haichang Wang, Huiqin Zhou, Zhi Liu, Tiancheng Zhao, Chunping Zhang.
      
    Keywords:  Ovarian stromal microenvironment; PCOS; Pathological changes; Stromal cells
    DOI:  https://doi.org/10.1186/s13048-026-02117-7
This page is being maintained by Thomas Krichel. It was last updated on 2026‒09‒01 at 0:49.