2. Academic Validation
  3. Induction of menstruation in mice reveals the regulation of menstrual shedding

Induction of menstruation in mice reveals the regulation of menstrual shedding

  • bioRxiv. 2025 Oct 9:2025.10.08.681007. doi: 10.1101/2025.10.08.681007.
Çağrı Çevrim 1,  Nicholas J Hilgert 2,  Aellah M Kaage 1,  Andrew J C Russell 1 3,  Allison E Goldstein 1 4,  Claire J Ang 1 2,  Jaina L R Gable 1 5,  Laura E Bagamery 6,  Ana Breznik 1 5,  Daniela J Di Bella 1,  Mustafa Talay 2 5,  Jingyu Peng 1 4,  Kathleen E O'Neill 7,  Fei Chen 1 3,  Sean R Eddy 2 5,  Kara L McKinley 1 5
Affiliations

Affiliations

  • 1 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge MA, 02138, USA.
  • 2 Department of Molecular and Cellular Biology, Harvard University, Cambridge MA, 02138, USA.
  • 3 Broad Institute, Cambridge MA 02142, USA.
  • 4 Biological and Biomedical Sciences Program, Harvard University, Cambridge MA, 02138, USA.
  • 5 Howard Hughes Medical Institute, Cambridge MA 02138, USA.
  • 6 Department of Systems Biology, Harvard University, Boston MA 02115, USA.
  • 7 Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia PA 19104.
PMID: 41332577 DOI: 10.1101/2025.10.08.681007
Abstract

During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this compartmentalization has been hindered by the lack of suitable animal models, as mice and rats do not menstruate. Here, we present transgenic mouse models that recapitulate the key anatomical, functional, and transcriptional features of human menstruation through targeted chemogenetic activation of premenstrual differentiation. Using single-cell spatial transcriptomics, we define a new paradigm for spatially regulated fibroblast differentiation that drives pre-menstrual endometrial layering and ultimately determines the extent of tissue shedding. Our results revise a century-old view of endometrial shedding and regeneration and establish new transgenic mice as powerful tools to advance menstruation research.

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