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2025 Faculty of Biomedical Sciences Frontiers in Toxicology

Endocrine disruption rewards: bisphenol-A induced reproductive toxicity and the precision ameliorative potential of flavonoids in preclinical studies. A systematic review and meta-analysis.

Okon M B,Fasongbon I V,Swase D, Dangana R S, Makena W, Ojiakor V O, Etukudo EM, Chebet J, Musyoka AM, Ifie SE, Mbyemeire H, Mbina SA, Ugwu OP-C, Oviosun A, Usman IM, Ifie JE, Rangasamy L, Olorunnisola OS, Mounmbegna P, Noreen S and Aja PM

Introduction: Bisphenol A (BPA), a pervasive endocrine-disrupting chemical,impairs male reproductive health via oxidative stress, hormonal dysregulation,and hypothalamic–pituitary–gonadal (HPG) axis disruption. Flavonoids,widely present in plant-derived foods and medicinal herbs, possessantioxidant and steroidogenic modulatory properties that may counteract BPAtoxicity, yet preclinical findings remain inconsistent. This study aims tosystematically evaluate and quantitatively synthesize preclinical evidenceon the protective effects of flavonoids against BPA-induced malereproductive toxicity.Methods: Using PRISMA 2020 guidelines, Web of Science, Scopus, andPubMed were searched up to September 2024. Eligible studies involvedBPA exposure in male rodents with flavonoid co-treatment and reportedreproductive endpoints. Hormonal and oxidative stress biomarkers werepooled using a random-effects model, expressed as standardized meandifferences (SMDs), with heterogeneity assessed by I2 statistics. Twenty studieswere included. Results: BPA significantly reduced testosterone (SMD = −4.91), estradiol(SMD = −2.72), follicle-stimulating hormone (FSH) (SMD = −7.71), and luteinizinghormone (SMD = −5.54), while increasing malondialdehyde and reducingantioxidant enzymes (SOD, CAT, GPx, and GSH).Discussion: Flavonoid co-treatment significantly improved hormonal profiles andoxidative balance, with the greatest recovery in FSH. High heterogeneity (I2 > 84%)reflected variability in doses, treatment duration, compound purity, and species.Flavonoids exhibit marked ameliorative potential against BPA-inducedreproductive toxicity in preclinical models, largely through hormonal regulationandoxidative stress mitigation. Standardized protocols and dose–response studiesare essential to enhance reproducibility and translational relevance.