Molecular Mechanisms of Arsenic and Microplastic-Induced Male Reproductive Toxicity and Potential Protective of Imperatorin: A Narrative Review
Background: Environmental contaminants such as arsenic and microplastics are increasingly associated with male reproductive dysfunction. This article reviews the mechanisms through which arsenic and microplastics affect male reproductive health and highlights the potential protective effects of imperatorin against co-exposure toxicity. Methods: A narrative literature review was conducted using studies published up to June 2026. Relevant experimental and observational studies were identified from major scientific databases to evaluate the effects of arsenic and microplastic exposure on male reproductive health. The review focused on the Nrf2/Keap1, NF-κB, p53, and steroidogenesis signalling pathways and their associated molecular markers involved in oxidative stress, inflammation, apoptosis, hormonal imbalance, and impaired spermatogenesis. The potential cytoprotective mechanisms of imperatorin against environmentally induced testicular injury were also examined. Results: Exposure to arsenic and microplastics negatively impacts male reproductive function by inducing excessive reactive oxygen species production, inhibiting antioxidant defence mechanisms, causing mitochondrial damage, activating inflammation, disrupting endocrine balance, and impairing spermatogenesis. Simultaneous exposure exacerbates oxidative stress, activates nuclear factor-kappa B-mediated inflammatory pathways, disrupts nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 signalling, and intensifies p53-dependent apoptosis. Microplastics may enhance the transit and storage of arsenic in testicular tissue, thus exacerbating its harmful effects on the male reproductive system. Conclusion: The presence of arsenic and microplastics in the environment may significantly affect male reproductive function. Growing evidence suggests that oxidative stress along with interconnected molecular pathways substantially contribute to the toxic effects observed during co-exposure.