PPARγ Regulates Triclosan Induced Placental Dysfunction

Exposure to the antibacterial agent triclosan (TCS) is associated with abnormal placenta growth and fetal development during pregnancy. Peroxisome proliferator-activated receptor gamma (PPAR gamma) is crucial in placenta development. However, the mechanism of PPAR gamma in placenta injury induced by TCS remains unknown. Herein, we demonstrated that PPAR gamma worked as a protector against TCS-induced toxicity. TCS inhibited cell viability, migration, and angiogenesis dose-dependently in HTR-8/SVneo and JEG-3 cells. Furthermore, TCS downregulated expression of PPAR gamma and its downstream viability, migration, angiogenesis-related genes HMOX1, ANGPTL4, VEGFA, MMP-2, MMP-9, and upregulated inflammatory genes p65, IL-6, IL-1 beta, and TNF-alpha in vitro and in vivo. Further investigation showed that overexpression or activation (rosiglitazone) alleviated cell viability, migration, angiogenesis inhibition, and inflammatory response caused by TCS, while knockdown or inhibition (GW9662) of PPAR gamma had the opposite effect. Moreover, TCS caused placenta dysfunction characterized by the significant decrease in weight and size of the placenta and fetus, while PPAR gamma agonist rosiglitazone alleviated this damage in mice. Taken together, our results illustrated that TCS-induced placenta dysfunction, which was mediated by the PPAR gamma pathway. Our findings reveal that activation of PPAR gamma might be a promising strategy against the adverse effects of TCS exposure on the placenta and fetus.

Automated summary

Exposure to the antibacterial agent triclosan (TCS) during pregnancy is associated with abnormal placenta growth and fetal development. This study demonstrates that peroxisome proliferator-activated receptor gamma (PPAR gamma) acts as a protector against TCS-induced toxicity. Activation of PPAR gamma could be a promising strategy to mitigate the adverse effects of TCS exposure on the placenta and fetus.