Multiomics profiling uncovers curdione-induced reproductive toxicity in HTR-8/SVneo cells

The assessment of medication toxicity and safety is pivotal during pregnancy. Curdione, a sesquiterpene compound extracted from <i>Curcumae Radix</i>, displays beneficial properties in terms of anti-inflammatory, tumor growth suppression, and anti-coagulative effects. However, its reproductive toxicity and precise mechanism remain unclear. This study aims to explore the mechanism of curdione-induced toxicity damage in HTR-8/SVneo cells through the epigenetics, proteomics, and metabolomics, and experimental verification. The results showed that curdione elicited alterations in m6A modification, gene expression, protein levels, and cellular metabolism of HTR-8/SVneo cells. Additionally, curdione induces oxidative stress, mitochondrial and DNA damage, while also downregulating the expression of Wnt6, β-catenin, ZO-1, and CLDN1 proteins. Curdione has the potential to modulate oxidative stress, mitochondrial dysfunction, and disruption of tight junctions via the Wnt/β-catenin signaling pathway, which contributes to cellular damage in HTR-8/SVneo cells.