Propylparaben Induces Reproductive Toxicity in Human Extravillous Trophoblast Cells via Apoptosis and Cell Cycle Pathways

Parabens (PBs), especially propylparaben, commonly used in consumer products, pose environmental and health concerns. This study explored propylparaben's cytotoxicity on HTR-8/SVneo human trophoblast cells, revealing significant dose-dependent cytotoxic effects, particularly post 48-h exposure. Elevated propylparaben levels triggered apoptosis, evidenced by increased Bax and activated Caspase-3, and induced the G0/G1 cell cycle arrest. Concurrently, an increase in reactive oxygen species and reduced mitochondrial membrane potential indicated oxidative stress and mitochondrial dysfunction. Although N-acetylcysteine (NAC) treatment reduced oxidative stress, cell invasiveness persisted, suggesting propylparaben might affect cell migration through nonoxidative mechanisms. Integrated transcriptome analysis through RNA sequencing revealed 3488 differentially expressed genes affected by propylparaben, highlighting changes in pathways like apoptosis and cell cycle regulation and identifying seven hub genes as potential biomarkers for pregnancy-related complications. This study comprehensively demonstrates the cytotoxic effects of propylparaben on human trophoblast cells, notably through apoptosis induction and cell cycle disruption, thereby providing crucial insights into its potential risks for reproductive health.