A systematic review on the impact of micro-nanoplastics on human health: Potential modulation of epigenetic mechanisms and identification of biomarkers.

Epigenetic-mediated modifications, induced by adverse environmental conditions, significantly alter an organism's physiological mechanisms. Even after elimination of the stimulus, these epigenetic modifications can be inherited through mitosis, thereby triggering transgenerational epigenetics. Plastics, with their versatile properties, are indispensable in various aspects of daily life. However, due to mismanagement, plastics have become so ubiquitous in the environment that no ecosystem on Earth is free from micro-nanoplastics (MNPs). This situation has raised profound concerns regarding their potential impact on human health. Recently, both in vivo animal and in vitro human cellular models have shown the potential to identify the harmful effects of MNPs at the genome level. The emerging epigenetic impact of MNP exposure is characterized by short-term alterations in chromatin remodelling and miRNA modulation. However, to understand long-term epigenetic changes and potential transgenerational effects, substantial and more environmentally realistic exposure studies are needed. In the current review, the intricate epigenetic responses, including the NHL-2-EKL-1, NDK-1-KSR1/2, and WRT-3-ASP-2 cascades, wnt-signalling, and TGF- β signalling, established in model organisms such as C. elegans, mice, and human cell lines upon exposure to MNPs, were systematically examined. This comprehensive analysis aimed to predict human pathways by identifying human homologs using databases and algorithms. We are confident that various parallel miRNA pathways, specifically the KSR-ERK-MAPK pathway, FOXO-Insulin cascade, and GPX3-HIF-α in humans, may be influenced by MNP exposure. This influence may lead to disruptions in key metabolic and immune pathways, including glucose balance, apoptosis, cell proliferation, and angiogenesis. Therefore, we believe that these genes and pathways could serve as potential biomarkers for future studies. Additionally, this review emphasizes the origin, dispersion, and distribution of plastics, providing valuable insights into the complex relationship between plastics and human health while elaborating on the epigenetic impacts.