| Autor: |
Madsen, Julie Feld, Ernst, Emil Hagen, Amoushahi, Mahboobeh, Dueholm, Margit, Ernst, Erik, Lykke-Hartmann, Karin |
| Předmět: |
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| Zdroj: |
Communications Biology; 6/20/2024, Vol. 7 Issue 1, p1-14, 14p |
| Abstrakt: |
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. An AMPK inhibitor accelerates activation of dormant follicles in murine in vitro-cultured ovaries, accompanied with an upregulation of Wnt and FOXO genes, phosphorylation of β-catenin, and successful egg maturation in vitro. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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