Metformin improves d-galactose induced premature ovarian insufficiency through PI3K-Akt-FOXO3a pathway.
Adv Med Sci
; 69(1): 70-80, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38387407
ABSTRACT
PURPOSE:
Metformin (MET), a first-line treatment for type 2 diabetes mellitus, restores ovarian function in women with polycystic ovary syndrome. MET has been shown to increase the rate of success for in vitro fertilization when utilized in assisted reproductive technologies. This study was designed to examine the impact of MET on ovarian function and fertility in a mouse model of galactose-induced premature ovarian insufficiency (POI). We further investigated the underlying mechanisms. MATERIALS ANDMETHODS:
Female mice were divided into 4 groups saline, d-galactose, d-galactose â+ âMET, and MET. Body weight, ovarian index, and fertility were assessed. The hormonal profile was done. Advanced glycation end products (AGEPs), receptor for advanced glycation end products (RAGE), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), forkhead box O3a (FOXO3a) expression were measured. Ovarian follicle counting and morphology were analyzed. Immunohistochemistry of cleaved caspase-3 expression was performed.RESULTS:
Our findings demonstrated that MET reversed irregularities in the estrus cycle, enhanced the ovarian index, and improved the abnormal levels of hormones and AGEs induced by d-galactose. Furthermore, the expression levels of PI3K, Akt, FOXO3a, and RAGE were upregulated with d-galactose. However, MET attenuated their expression levels. The primordial follicles ratio was improved, whereas atretic follicles and apoptotic-related cleaved caspase-3 expression were decreased in the d-galactose â+ âMET group compared to the d-galactose group.CONCLUSION:
This study demonstrates that MET partially rescued ovarian dysfunction and apoptosis induced by d-galactose via a mechanism involving PI3K-Akt-FOXO3a pathway. Our finding proposed that MET may be a promising alternative treatment for POI.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Primary Ovarian Insufficiency
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Forkhead Box Protein O3
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Galactose
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Metformin
Limits:
Animals
Language:
En
Journal:
Adv Med Sci
Journal subject:
MEDICINA
Year:
2024
Document type:
Article