Quercetin prevents primordial follicle loss via suppression of PI3K/Akt/Foxo3a pathway activation in cyclophosphamide-treated mice.
Reprod Biol Endocrinol
; 19(1): 63, 2021 Apr 23.
Article
in En
| MEDLINE
| ID: mdl-33892727
ABSTRACT
BACKGROUND:
Chemotherapy improves the survival rates of patients with various cancers but often causes some adverse effects, including ovarian damage, characterised by a decrease in primordial follicle stockpiles. Recent studies have revealed that chemotherapy may stimulate the PI3K signalling pathway, thereby resulting in accelerated primordial follicle activation and a decreased ovarian reserve. Quercetin is an inhibitor of the PI3K pathway; however, its protective effects against chemotherapy-induced follicle loss in mice have not been established. In this study, the effects of quercetin in a mouse model of cyclophosphamide-induced ovarian dysfunction were investigated.METHODS:
C57BL/6 female mice were used for the study. Paraffin sections of mouse ovaries (n = 30 mice) were stained with haematoxylin and eosin for differential follicle counts. Apoptosis (n = 5 mice per group) was evaluated by TUNEL assay. Immunohistochemical staining for ki67 and Foxo3a (n = 5 mice per group) was performed to evaluate the activation of primordial follicles. The role of the PI3K signalling pathway in the ovaries (n = 45 mice) was assessed by western blotting.RESULTS:
Quercetin attenuated the cyclophosphamide-induced reduction in dormant primordial follicles. Analysis of the PI3K/Akt/Foxo3a pathway showed that quercetin decreased the phosphorylation of proteins that stimulate follicle activation in cyclophosphamide-induced ovaries. Furthermore, quercetin prevented cyclophosphamide-induced apoptosis in early growing follicles and early antral follicles, maintained anti-Müllerian hormone levels secreted by these follicles, and preserved the quiescence of the primordial follicle pool, as determined by intranuclear Foxo3a staining.CONCLUSIONS:
Quercetin attenuates cyclophosphamide-induced follicle loss by preventing the phosphorylation of PI3K/Akt/Foxo3a pathway members and maintaining the anti-Müllerian hormone level through reduced apoptosis in growing follicles. Accordingly, quercetin is expected to improve fertility preservation and the prevention of endocrine-related side effects of chemotherapy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quercetin
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Apoptosis
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Cyclophosphamide
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Ovarian Follicle
Limits:
Animals
Language:
En
Journal:
Reprod Biol Endocrinol
Journal subject:
ENDOCRINOLOGIA
/
MEDICINA REPRODUTIVA
Year:
2021
Document type:
Article
Country of publication:
ENGLAND
/
ESCOCIA
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GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM