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Dorsomorphin inhibits AMPK, upregulates Wnt and Foxo genes and promotes the activation of dormant follicles.
- Source :
-
Communications biology [Commun Biol] 2024 Jun 20; Vol. 7 (1), pp. 747. Date of Electronic Publication: 2024 Jun 20. - Publication Year :
- 2024
-
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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Mice
Humans
Up-Regulation drug effects
Forkhead Transcription Factors metabolism
Forkhead Transcription Factors genetics
Wnt Proteins metabolism
Wnt Proteins genetics
beta Catenin metabolism
beta Catenin genetics
Phosphorylation drug effects
Mice, Inbred C57BL
Metformin pharmacology
Wnt Signaling Pathway drug effects
Ovarian Follicle drug effects
Ovarian Follicle metabolism
AMP-Activated Protein Kinases metabolism
AMP-Activated Protein Kinases genetics
Pyrimidines pharmacology
Pyrazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 38902324
- Full Text :
- https://doi.org/10.1038/s42003-024-06418-9