Multi-omics integration reveals human placental molecular signatures associated with microplastics exposure

Abstract

Abstract Background Microplastics (MPs) are pervasive environmental contaminants that have been increasingly detected in human tissues. However, their molecular effects on the human placenta, a critical interface for maternal–fetal exchange and fetal development, remain poorly understood. This study aimed to characterize the placental microplastic burden and to investigate transcriptomic, proteomic, and metabolomic alterations associated with different levels of MPs exposure using an integrated multi-omics approach. Methods MPs were systematically quantified in human placental tissues using pyrolysis–gas chromatography–mass spectrometry. Placental samples were stratified into high- and low-burden groups according to MPs exposure levels. Integrated transcriptomic, proteomic, and metabolomic analyses were then performed to identify exposure-associated molecular perturbations. The DIABLO framework was applied to integrate multi-omics datasets and identify discriminatory cross-omics features, followed by network analysis to explore key regulatory hubs and pathways. Results Placental tissues with higher MP burden exhibited multi-layer molecular perturbations involving immune dysregulation, antifolate resistance, oxidative stress, and altered lipid and purine metabolism. Integrative DIABLO analysis identified a set of cross-omics features that robustly distinguished the high- and low-burden groups, including MINPP1 , PARG , NDUFS6, and cinnamoside. Network analysis further positioned NDUFS6 as a central hub connecting transcriptomic, proteomic, and metabolomic changes, suggesting that mitochondrial dysfunction may represent a key axis of placental response to MPs exposure. Conclusions These findings provide a systems-level understanding of placental molecular alterations associated with MPs exposure and highlight potential pathways and regulatory factors that may contribute to the effects of environmental exposure on maternal–fetal health.