Elucidating the Mechanism of Polyethylene Terephthalate Micro / Nanoplastics Inducing Gestational Diabetes Mellitus through Network Toxicology and Molecular Docking Analysis

Abstract

This study investigated polyethylene terephthalate-derived micro/nanoplastics (PET-MNPs), a predominant plastic pollutant in the circulatory system, employing network toxicology and molecular docking approaches to systematically elucidate their molecular mechanisms in gestational diabetes mellitus (GDM) pathogenesis. We identified 35 potential PET-MNPs-GDM interaction targets and demonstrated that PET-MNPs primarily disrupt insulin signaling through four key pathways: (1) cellular metabolic adaptation (amino acid starvation response), (2) hypoxic stress responses (HIF-1 signaling pathway), (3) vascular homeostasis (fluid shear stress and atherosclerosis pathways), and (4) proliferative signaling networks (oncogenic pathways). Network topology analysis pinpointed STAT1, PIK3R1, and PTPN11 as core regulatory nodes, with molecular docking confirming strong binding affinity between PET-MNPs and these targets. For the first time, this study establishes PET-MNPs as environmental metabolic disruptors that exacerbate GDM through multi-target and multi-pathway mechanisms, providing crucial theoretical insights into plastic pollution-metabolic disease relationships. Our findings underscore the urgent need for population-based epidemiological studies and targeted intervention strategies, highlighting significant public health implications for protecting vulnerable populations.