Abstract
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•Human exposure to Bisphenol A always results via leaching from polycarbonate plastic packages. BPA has been proved to be an estrogen receptor agonist with subsequent feminizing biological effects.•Bisphenol A has an endocrine disruptive chemical effect by modulating the expression of genes affecting gonadal development.•The use of mesenchymal stem cells (MSCs) exhibits unique therapeutic values because they have great potential to support the regeneration and differentiation of cells and tissues leading to replacement of tissues destroyed by different injurious stimuli.•Resveratrol is a natural phytoalexin present in many plants. Resveratrol exerts beneficial effects as anti-atherosclerotic, anti-inflammatory, anti-carcinogenic, and antioxidant properties.•Resveratrol has significant protective effects against ovarian and uterine damage induced by methotrexate, irradiation, and other injurious agents.
The probable beneficial effects of mesenchymal stem cells (MSCs) and resveratrol were assessed in an experimental model of Bisphenol-A (BPA)-evident uterine damage in rats. Thirty-five albino rats were involved and equally divided into five groups: Group I: negative control rats received usual diet, Group II: positive control rats received BPA by oral gavage for 15 days, Group III: BPA-treated rats received single oral gavage of resveratrol daily for two weeks, Group IV: BPA-treated rats received a single intravenous dose of MSCs and Group V: BPA-treated rats received combined treatment of resveratrol and MSCs. Oxidative stress markers, apoptosis-related genes, and gonadal hormones were assessed. Histological and immunohistochemical examination of uterine tissue was conducted for TGF-β 1. Caspases-3, 8, and 9 (Casp3, Casp8, Casp9) genes were assessed in uterine tissues by quantitative real-time PCR. Results revealed that BPA induced significant changes in the endometrial tissue, inflammatory cell infiltration, focal blood extravasation, increase in collagen fibers, decrease in PAS staining, and increase in TGF-β 1 immunoreactivity. BPA also induced a significant increase in oxidative stress markers; malondialdehyde (MDA), SOD, CAT, and apoptosis-related genes. BPA induced a significant change in blood levels of gonadal hormones; a significant increase in FSH and a significant decrease in estradiol (E2) and progesterone (P). Treatment with either resveratrol, MSCs, or a combination of them resulted in significant enhancement of histological findings, restoration of gonadal hormones to near-normal levels, and a significant decrease in oxidative stress markers and apoptosis genes. Combined treatment with resveratrol and MSCs demonstrated more significant therapeutic effects as regard to the studied parameters in association with rat groups treated with either MSCs or resveratrol separately.