Intracellular fate of micro- and nanoplastics in human placenta: Organelle-specific toxicity and mechanistic convergence.

Abstract

Detection of micro- and nanoplastics (MNPs) in human placental tissue, fetal cord blood, and neonatal meconium marks a paradigm shift in prenatal exposure research. Yet the field lacks a mechanistic framework integrating the intracellular stress responses MNPs provoke subcellularly. This narrative review proposes an organelle-resolved model of MNP-induced cellular toxicity wherein internalized MNPs traffic through the endosomal-lysosomal system, initiating lysosomal overload and autophagic flux blockade, mitochondrial cristae disorganization consistent with ΔΨm collapse, and endoplasmic reticulum cisternal dilation with pro-apoptotic UPR switching. These converge into a unified framework - the chronic 'Plasticenta' cell danger response (cPCDR) - wherein MNP persistence is hypothesized to generate a perpetually re-triggered, incompletely resolved danger state. The Pi-GAC-glutaminolysis axis is proposed as a secondary metabolic convergence downstream of ΔΨm collapse. Contextualized within the DoHaD framework, the fetoplacental unit is positioned as a critical transgenerational MNP biosensor. Priority directions include scRNA-seq-based cPCDR validation, trophoblast organoid models, and prospective placental biobanking.