Human exposure to micro- and nanoplastics: a mechanistic perspective of health risks associated with metabolic and reproductive functions

The ever-increasing manufacture, abundance, usage, and fragmentation of plastics and their residues in foods and beverages and rapid rises in air pollution dramatically increased micro- and nanoplastics (MNPs) exposure that could affect human health as these MNPs contain endocrine-disrupting chemicals and other harmful substances, and found their traces in almost all of the human organs. Multiple mechanisms are postulated for the biodegradation of MNPs in the human body. Once reaching the gastrointestinal tract, MNPs are translocated and enter tissue through cellular internalization via endocytosis. This process depends on the size, charge, density, and functional groups of the MNPs, which determine the rate of uptake and internalization. MNPs enter the circulatory system from the gut, where innate immune cells and macrophages engulf these MNPs via phagocytosis. Recent clinical data have identified the accumulation of MNPs as nanoscale fragments in the deceased human brain, at levels significantly higher than those found in the liver and kidneys, indicating that an in-depth understanding of their exposure, uptake, and clearance is essential. Although several reviews have been compiled in the recent past, comprehensive mechanistic consolidation on exposure assessment due to its ingestion, integration, bioaccumulation, detection, interaction on gut microbiota, and extracellular system, systemic, metabolic, and inflammatory response on pulmonary, endothelial, renal, and gonadal functions is limited. This review outlined the intricate mechanistic reactions of the target organs, whose functions could be altered due to MNPs exposure, warranting a comprehensive impact assessment of their exposure in the context of human metabolic and reproductive health and well-being. © 2025 Elsevier B.V.