Effects of quercetin on ovarian function and regulation of the ovarian PI3K/Akt/FoxO3a signalling pathway and oxidative stress in a rat model of cyclophosphamide-induced premature ovarian failure

Basic Clin Pharmacol Toxicol. 2022 Feb;130(2):240-253. doi: 10.1111/bcpt.13696. Epub 2021 Dec 8.


To investigate the ability of quercetin to improve ovarian function and inhibit ovarian oxidative stress through the PI3K/Akt/FoxO3a signalling pathway in a rat model of premature ovarian failure (POF), we constructed a POF rat model with cyclophosphamide (CTX) and treated it with quercetin. Haematoxylin and eosin staining (H&E staining) was used to observe the morphological changes of the ovaries. The serum levels of AMH, E2, FSH, SOD, GSH-Px and MDA were determined by enzyme-linked immunosorbent assays. The expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), forkhead box O3a (FoxO3a) and their phosphorylated forms AMH, FSH and their receptors in the ovary were detected by western blots. The mRNA expression of PI3K, Akt, FOXO3a, AMH, FSH and their receptors was detected by qRT-PCR. Our results showed that quercetin could significantly increase the expression of AMH, E2, SOD and GSH-Px, upregulate the protein expression of AMH, FSH and its receptor and decrease the expression ratio of phosphorylated PI3K, Akt, FOXO3a and the unphosphorylated forms. Moreover, quercetin inhibited the mRNA expression of PI3K, Akt and FOXO3a. These results suggest that quercetin can restore ovarian function and inhibit oxidative stress by regulating the PI3K/Akt/FoxO3a signalling pathway.

Keywords: PI3K/Akt/FoxO3a; POF; oxidative stress; quercetin.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / toxicity
  • Antioxidants / pharmacology
  • Cyclophosphamide / toxicity*
  • Disease Models, Animal
  • Female
  • Forkhead Box Protein O3 / metabolism
  • Oxidative Stress / drug effects*
  • Phosphatidylinositol 3-Kinase / metabolism
  • Primary Ovarian Insufficiency / drug therapy*
  • Primary Ovarian Insufficiency / physiopathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quercetin / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects


  • Antineoplastic Agents, Alkylating
  • Antioxidants
  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Cyclophosphamide
  • Quercetin
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt