Bisphenol-a induced reproductive toxicity: insights into endocrine disruption and epigenetic regulation

Abstract

Reproductive health depends on the precise regulation of hormonal balance, gene expression, and normal functioning of reproductive organs. However, increasing exposure to endocrine-disrupting chemicals (EDCs), particularly bisphenol-A (BPA), has emerged as a significant threat to reproductive integrity as it remains a vital benchmark and reference baseline in toxicology because it is one of the most widely studied endocrine disruptor, allowing scientists to compare the unverified safety profiles and similar hormonal risks of widespread substitutes like bisphenol S (BPS) and bisphenol F (BPF). BPA interferes with steroidogenic pathways, hormone receptor signaling, and the hypothalamic–pituitary–gonadal (HPG) axis, leading to disruption of estradiol, progesterone, and androgen homeostasis. In addition to endocrine interference, BPA induces epigenetic dysregulation through alterations in DNA methylation, histone modifications, and non-coding RNA expression. These molecular changes contribute to oxidative stress, and impaired cellular signaling, ultimately resulting in defective ovarian steroidogenesis, abnormal follicular development, infertility, and pregnancy complications. The present study aims to elucidate current evidence on the endocrine and epigenetic mechanisms underlying BPA-induced reproductive toxicity in both males and females. It further highlights the role of environmentally induced epigenetic modifications in mediating transgenerational reproductive effects.