Histomorphological Changes in a Rat Model of Polycystic Ovary Syndrome and the Contribution of Stevia Leaf Extract in Modulating the Ovarian Fibrosis, VEGF, and TGF-β Immunoexpressions: Comparison with Metformin

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of fertile females. It has been reported that stevia leaf extract (SLE) has antidiabetic and antihyperlipidemic properties. Therefore, the current study hypothesized and investigated the role and mechanistic aspects of a natural sweetener; SLE in treating a rat model of letrozole-induced PCOS and to compare it with metformin. Thirty-five female Wistar albino rats were divided into 5 groups: control, PCOS-induced group (letrozole, 1 mg/kg/d, for 21 days), SLE, metformin, and combination-treated groups (300 mg/kg/d, for the next 28 days in SLE and metformintreated groups). Vaginal smears were done. The levels of glucose, lipid, and hormonal profiles were measured in the serum meanwhile, malonyl dialdehyde (MDA), superoxide dismutase (SOD), and tumour necrosis factor (TNF-α) were measured in the ovary. Ovarian sections were subjected to hematoxylin and eosin, Masson, and immunohistochemical identification of VEGF and TGF-β followed by morphometric analysis. PCOS rats showed altered hormonal and lipid profiles, in addition to hyperglycemia. Also, the ovarian tissue levels of MDA and TNF-α were elevated, and SOD was decreased. Numerous cystic follicles, decrease/absence of corpora lutea, interstitial fibrosis with positive VEGF and TGF-β immunoreactivity were evident. SLE improved all altered parameters. SLE showed potential therapeutic merits in letrozole-induced PCOS via anti-inflammatory, antioxidant, anti-fibrotic, and angiogenesis regulating mechanisms. Its effects were almost comparable to metformin, and the combination of both has no further synergistic effect.

Antioxidant Activity of Leaf Extracts from Stevia rebaudiana Bertoni Exerts Attenuating Effect on Diseased Experimental Rats: A Systematic Review and Meta-Analysis

“…A thorough literature search for antioxidant activity of stevia resulted in 184 articles. After screening of titles and abstracts, and compliance with the PRISMA guidelines (http://www.prisma-statement.org/ (accessed on 26 January 2023)) (Figure 2), 22 articles were found to satisfy the eligibility criteria [41,42,44,45,[55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72]. Seventeen records were additionally retrieved from screening lists of references, and two of them [37,73] were enrolled in the meta-analysis, making a total of 24 articles, which contained 104 studies in total.…”

Therapeutic Effect of Quercetin in Letrozole Induced Polycystic Ovary Syndrome in Rat Model

“…There were also significant decreased cystic follicles. The improved ovarian histoarchitecture could be related to the antiandrogenic property of the treatment options [40] .…”

“…However, there was no significant difference between these treatments and metformin treatment for the amount of Masson-stained collagen fibers and TGF-0 immune-expression. Literature has suggested that metformin has an antifibrotic impact in a number of organs, including the ovarian fibrosis caused by dehydroepiandrosterone [40] .…”

Ameliorating effects of adropin on letrozole‐induced polycystic ovary syndrome via regulating steroidogenesis and the microbiota inflammatory axis in rats

“…For each image, a line was drawn to mark the granulosa and theca cell layers, and then analyses and set measurements were performed to determine their thickness. Finally, the mean values from each slide were calculated (Morsi et al., 2022). In addition, intestinal claudin‐1 staining intensity was assessed by processing images of intestinal sections to determine the intensity of claudin‐1 staining.…”