Abstract

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, possess
antioxidant and steroidogenic modulatory properties that may counteract BPA
toxicity, yet preclinical findings remain inconsistent. This study aims to
systematically evaluate and quantitatively synthesize preclinical evidence
on the protective effects of flavonoids against BPA-induced male
reproductive toxicity.
Methods: Using PRISMA 2020 guidelines, Web of Science, Scopus, and
PubMed were searched up to September 2024. Eligible studies involved
BPA exposure in male rodents with flavonoid co-treatment and reported
reproductive endpoints. Hormonal and oxidative stress biomarkers were
pooled using a random-effects model, expressed as standardized mean
differences (SMDs), with heterogeneity assessed by I2 statistics. Twenty studies
were included. Results: BPA significantly reduced testosterone (SMD = −4.91), estradiol
(SMD = −2.72), follicle-stimulating hormone (FSH) (SMD = −7.71), and luteinizing
hormone (SMD = −5.54), while increasing malondialdehyde and reducing
antioxidant enzymes (SOD, CAT, GPx, and GSH).
Discussion: Flavonoid co-treatment significantly improved hormonal profiles and
oxidative 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-induced
reproductive toxicity in preclinical models, largely through hormonal regulation
andoxidative stress mitigation. Standardized protocols and dose–response studies
are essential to enhance reproducibility and translational relevance.