Micro- and nanoplastic (MNPs) exposure at single-cell resolution impaired placental function and cellular dynamics

The placenta is crucial for a successful pregnancy, acting as a protective barrier for fetal health. Growing evidence suggests that pregnant women are widely exposed to micro- and nanoplastics (MNPs), which have been implicated in placental dysfunction associated with pregnancy complications and adverse offspring outcomes. To investigate this, we characterized MNPs-induced placental cellular dynamics at the single-cell level. Our analysis of placental tissue identified 14 major cell types, including trophoblasts and immune cells. Comparative transcriptomics between control and MNPs-exposed groups revealed significant alterations in subpopulations of trophoblasts, macrophages, and fibroblasts, indicating an adaptive response to toxic stress. Specifically, we observed a marked upregulation of genes related to endoplasmic reticulum stress and xenobiotic clearance in trophoblasts, and of ECM remodeling pathways in fibroblasts. This was supported by the integration of metabolomic and proteomic data, which detailed the accompanying molecular cascades. We propose that while these processes represent an attempt to maintain placental homeostasis, prolonged or high-level MNP exposure may overwhelm such compensatory mechanisms, ultimately leading to dysfunction. Consequently, our study provides a foundational resource for understanding the cellular mechanisms of MNP-induced placental toxicity and establishes a basis for future research into protective strategies against environmental reproductive toxicants.