Endocrine disruptors and male reproductive health: mechanisms, epigenetics, and clinical perspectives

Concepción-Zavaleta M.J.; Villanueva-De La Cruz J.P.; Rodríguez-Soto J.C.; Fuentes-Mendoza J.; Coronado-Arroyo J.; Concepción-Urteaga L.; Quiroz-Aldave J.; Paz-Ibarra J. · Revista Internacional de Andrologia (2026) · DOI: 10.22514/j.androl.2026.015

Resumen

Male infertility, a pressing public health issue, is increasingly linked to exposure to endocrine-disrupting chemicals (EDCs), such as phthalates, bisphenol A (BPA), organochlorines, pesticides, as well as natural EDCs such as phytoestrogens. This review synthesizes mechanistic and translational evidence on how EDCs impair male reproductive function through multifaceted pathways. EDCs disrupt the hypothalamic-pituitary-gonadal (HPG) axis, induce cytotoxic effects in Leydig and Sertoli cells, and impair steroidogenesis and spermatogenesis, leading to clinically significant reductions in sperm concentration, motility, and morphology. Emerging data highlight transgenerational effects via epigenetic modifications, including altered DNA methylation and microRNA expression, which may perpetuate infertility across generations. We critically evaluate epidemiological and experimental studies, revealing consistent associations between EDC exposure and adverse reproductive outcomes, such as cryptorchidism, testicular cancer, and idiopathic infertility. Notably, prenatal and perinatal exposure windows exhibit heightened vulnerability, with lifelong consequences. Despite progress, key gaps persist in understanding low-dose mixture effects, interindividual susceptibility, and the interplay between EDCs and lifestyle factors (e.g., oxidative stress, psychosocial stressors). Clinically, this review underscores the need for enhanced biomonitoring to quantify real-world EDC exposures and their interactions, mechanistic research elucidating dose-response relationships and non-monotonic effects, and evidence-based policies to regulate EDCs in consumer products, agriculture, and healthcare. We propose a translational framework integrating high-throughput toxicology, epigenetic biomarkers, and clinical interventions to mitigate risks. Addressing these challenges is urgent to safeguard male reproductive health amid rising global infertility rates. Future research should also explicitly consider the role of natural endocrine-disrupting compounds, particularly phytoestrogens, in shaping male reproductive outcomes.

Instituciones: Universidad Nacional Mayor de San Marcos; Universidad Nacional de Trujillo; Universidad Científica del Sur