Molecular Mechanisms and Developmental Effects of Endocrine Disruptors on Male Reproductive Health and Mitigation Strategies to Reduce Their Adverse Effects

Abstract

Over the past decades, male reproductive health has markedly declined, as evidenced by reduced sperm concentration, impaired motility, increased morphological abnormalities, and a higher incidence of testicular disorders. Environmental factors, particularly endocrine disruptors (EDs), are increasingly recognized as important contributors due to their ability to interfere with hormonal signaling and cellular homeostasis. Mechanistically, EDs induce oxidative stress, mitochondrial dysfunction, DNA damage, endocrine imbalance, and epigenetic reprogramming. These alterations include changes in DNA methylation, histone modifications, and non-coding RNA expression that may persist beyond the period of direct exposure and potentially affect subsequent generations. In parallel, EDs disrupt the hypothalamic–pituitary–gonadal axis, impair steroidogenesis, and compromise Sertoli cell function and blood–testis barrier integrity. This part of review also discusses emerging strategies to mitigate ED-induced reproductive toxicity, including antioxidants, natural bioactive compounds, probiotics, and other interventions targeting oxidative stress, apoptosis, and endocrine dysfunction. Collectively, these findings highlight the complex molecular, epigenetic, and endocrine mechanisms underlying ED-induced male reproductive dysfunction and its potential long-term consequences.