Gestational Exposure to the Food Processing Contaminant 3-MCPD Impairs Fetal Growth by Disrupting Placental Taurine Metabolism to Drive Vascular Senescence

Abstract

Abstract 3-Monochloro-1,2-propanediol (3-MCPD), a common food contaminant, induces fetal growth restriction in mice by triggering senescence in the placental vasculature. Transcriptomic analysis reveals suppression of the taurine–hypotaurine pathway through downregulation of Fmo1. Mechanistically, 3-MCPD upregulates Ezh2, which deposits repressive H3K27me3 marks at the Fmo1 promoter, silencing its transcription and depleting placental taurine. Taurine supplementation or Ezh2 inhibition rescues 3-MCPD-induced vascular senescence in human endothelial cells. These findings identify an Ezh2–taurine axis essential for placental vascular health, and establish a mechanistic framework for how a widespread food pollutant disrupts this pathway to cause adverse pregnancy outcomes. This work highlights taurine as a potential nutritional intervention against 3-MCPD developmental toxicity, offering a dietary strategy for protecting at-risk pregnancies.