Endocrine-Disrupting Chemicals and Male Infertility: Mechanisms, Risks, and Regulatory Challenges
Sofoklis Stavros, Nikolaos Kathopoulis, Efthalia Moustakli, Anastasios Potiris, Ismini Anagnostaki, Spyridon Topis, Nefeli Arkouli, Konstantinos Louis, Charalampos Theofanakis, Themos Grigoriadis, Nikolaos Thomakos, Athanasios Zikopoulos
Abstract
Male reproductive health is increasingly threatened by endocrine-disrupting chemicals (EDCs), which interfere with hormonal homeostasis and reproductive physiology. Rising rates of male infertility have been linked to greater exposure to pollutants such as heavy metals, phthalates, pesticides, and bisphenol A. These compounds act through multiple mechanisms, including oxidative stress, apoptosis, receptor-mediated disruption of estrogenic and androgenic signaling, alterations in the hypothalamic-pituitary-gonadal (HPG) axis, and heritable epigenetic changes. Such disruptions impair key outcomes like sperm concentration, motility, morphology, DNA integrity, and steroidogenesis. Evidence from animal studies and human epidemiology consistently demonstrates these harmful effects, with biomarkers of EDC exposure correlating with reduced semen quality, hormonal imbalances, and infertility. Beyond individual health, infertility linked to EDCs carries significant social and economic costs. This review evaluates regulatory frameworks, highlights methodological challenges in risk assessment, and synthesizes mechanistic and clinical evidence. Particular attention is given to unresolved issues such as non-monotonic dose responses, mixture effects, low-dose exposures, and transgenerational impacts. Future priorities include refining biomonitoring, addressing mixture risks, and strengthening international regulation. By integrating mechanistic, clinical, and policy insights, this review underscores the urgent need for strategies to mitigate EDC-related threats to male reproductive health.