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Establishing 3D Endometrial Organoids from the Mouse Uterus
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Investigating Aging-Related Endometrial Dysfunction Using Endometrial Organoids.

Minghui Lu1,2,3,4,5,6,7, Yanli Han1,2,3,4,5,6,7, Yu Zhang1,2,3,4,5,6,7

  • 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.

Cell Proliferation
|December 18, 2024
PubMed
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Endometrial aging impairs reproductive health due to fibrosis and reduced receptivity. The PI3K-AKT-FOXO1 pathway is overactivated in aging endometrium, offering potential therapeutic targets.

Area of Science:

  • Reproductive biology
  • Cellular aging
  • Molecular mechanisms of aging

Background:

  • Endometrial aging significantly impacts female reproductive health.
  • The precise molecular mechanisms underlying endometrial aging are not fully understood.
  • Age-associated functional decline, including fibrosis and reduced receptivity, occurs even in reproductive-aged females.

Purpose of the Study:

  • To elucidate the molecular mechanisms of endometrial aging.
  • To identify novel therapeutic targets for improving endometrial function in aging females.
  • To investigate the role of the PI3K-AKT-FOXO1 signaling pathway in endometrial aging.

Main Methods:

  • Transcriptome profiling (RNA-seq) of endometrium and endometrial organoids from young and advanced age females.
Keywords:
PI3K/AKT/FOXO1endometrial ageingfibrosisinflammationorganoidsreceptivity

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  • Experimental validation of age-associated molecular changes.
  • Pharmacological manipulation of the PI3K-AKT-FOXO1 pathway.

    • Main Results:

    • Identified age-associated molecular changes including fibrosis, imbalanced inflammation (Th1 bias), cellular senescence, and altered signaling pathways.
    • Uncovered overactivation of the PI3K-AKT-FOXO1 signaling pathway in aging endometrium.
    • Demonstrated that modulating PI3K activity (LY294002 or 740Y-P) affects endometrial organoid function, correlating with aging phenotypes.

    Conclusions:

    • Endometrial aging is characterized by fibrosis, diminished receptivity, and specific molecular alterations.
    • The PI3K-AKT-FOXO1 pathway is a key player in endometrial aging, linked to fibrosis and impaired receptivity.
    • Targeting the PI3K-AKT-FOXO1 pathway presents a potential strategy to improve reproductive outcomes in women of advanced reproductive age.