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

Abstract

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.

Human Umbilical Cord Mesenchymal Stem Cells Improve Premature Ovarian Failure through Cell Apoptosis of miR-100-5p/NOX4/NLRP3

“…Its main function is to maintain the function of the female reproductive system and the secretion of hormones [ 23 ]. The imbalance of free radical metabolism caused by endemic fluorosis and the damage of organ function caused by the accumulation of a large number of oxidative stress products have always been a hot issue for researchers [ 23 ]. Oxidative stress injury will promote the production of inflammatory factors [ 24 ].…”

“…NLRP3 can promote the secretion of proinflammatory cytokines, aggravate cell damage, and induce cell death [32,33]. Inhibiting NLRP3 inflammatory signal can reduce inflammatory response and protect tissues, promote the release of anti-inflammatory cytokine IL-10 and proinflammatory cytokine IL-21 levels in serum, improve the inflammatory response of ovary, and reduce the inflammatory injury of follicle and the decline of ovarian reserve function [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. This study showed that the HUCMSCs suppressed NOX4, NLRP3, and GSDMD protein expression levels in the in vitro model.…”

Comparison of Animal Models for Premature Ovarian Insufficiency Induced by Different Doses of Cyclophosphamide: a Network Meta‑analysis

“…After carefully reviewing the full-text review ,13 studies were excluded due to the discrepancy of inclusion and exclusion criteria mentioned above. 14 studies [9][10][11][12][13][14][15][16][17][18][19][20][21][22] were nally selected for meta-analysis. A PRISMA ow diagram describing the process of literature search and selection is presented in Fig.…”

The impact of herbal medicine in regulating intestinal flora on female reproductive disorders

“…Furthermore, quercetin is also a class of flavonoid natural compounds with anti-inflammatory, antioxidant, anti-obesity and anti-cancer properties. Studies have shown that quercetin can intervene in the development of PCOS, EMs and POI in a multi-targeted and multi-pathway manner (Park et al, 2019;Chen et al, 2022;Zheng et al, 2022), while quercetin supplementation significantly increased the relative abundance of Akkermansia and reduced the ratio of F/B in obese mice (Tan et al, 2021), improved LPS-induced inflammatory damage (Bian et al, 2018), maintained glucolipid metabolic and promoting the production of SCFAs to enhance insulin sensitivity and improve the inflammatory response. Therefore, we hypothesize that quercetin may ameliorate reproductive endocrine disorders by reshaping the structure of the intestinal flora and increasing the content of SCFAs.…”