2. Academic Validation
  3. Dorsomorphin inhibits AMPK, upregulates Wnt and Foxo genes and promotes the activation of dormant follicles

Dorsomorphin inhibits AMPK, upregulates Wnt and Foxo genes and promotes the activation of dormant follicles

  • Commun Biol. 2024 Jun 20;7(1):747. doi: 10.1038/s42003-024-06418-9.
Julie Feld Madsen 1,  Emil Hagen Ernst 2 3,  Mahboobeh Amoushahi 1,  Margit Dueholm 2,  Erik Ernst 1 4,  Karin Lykke-Hartmann 5 6
Affiliations

Affiliations

  • 1 Department of Biomedicine, Aarhus University, DK-8000, Aarhus C, Denmark.
  • 2 Department of Obstetrics and Gynaecology, Aarhus University Hospital, DK-8000, Aarhus C, Denmark.
  • 3 Department of Gynaecology and Obstetrics, Gødstrup Hospital, DK-7400, Herning, Denmark.
  • 4 Fertility Clinic Regional Hospital Horsens, DK-8700, Horsens, Denmark.
  • 5 Department of Biomedicine, Aarhus University, DK-8000, Aarhus C, Denmark. kly@biomed.au.dk.
  • 6 Department of Clinical Genetics, Aarhus University Hospital, DK-8200, Aarhus N, Denmark. kly@biomed.au.dk.
PMID: 38902324 DOI: 10.1038/s42003-024-06418-9
Abstract

AMPK is a well-known energy sensor regulating cellular metabolism. Metabolic disorders such as obesity and diabetes are considered detrimental factors that reduce fecundity. Here, we show that pharmacologically induced in vitro activation (by metformin) or inhibition (by dorsomorphin) of the AMPK pathway inhibits or promotes activation of ovarian primordial follicles in cultured murine ovaries and human ovarian cortical chips. In mice, activation of primordial follicles in dorsomorphin in vitro-treated ovaries reduces AMPK activation and upregulates Wnt and FOXO genes, which, interestingly, is associated with decreased phosphorylation of β-catenin. The dorsomorphin-treated ovaries remain of high quality, with no detectable difference in Reactive Oxygen Species production, Apoptosis or mitochondrial cytochrome c oxidase activity, suggesting safe activation. Subsequent maturation of in vitro-treated follicles, using a 3D alginate Cell Culture system, results in mature metaphase eggs with protruding polar bodies. These findings demonstrate that the AMPK pathway can safely regulate primordial follicles by modulating Wnt and FOXO genes, and reduce β-catenin phosphorylation.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-112083
    99.66%, AMPK抑制剂
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