Triclosan-induced trophoblast dysfunction is associated with activation of the circKAT6B/miR-204-5p/TCF12-PCDH9 axis during early pregnancy.

Triclosan (TCS), a widely used antimicrobial compound, has been associated with adverse reproductive outcomes, but the underlying post-transcriptional mechanisms remain unclear. In this study, pregnant mice were exposed to TCS from gestational day (GD) 0.5 to GD 13.5. TCS exposure reduced implantation sites at GD 5.5 and increased embryonic resorption at GD 13.5, accompanied by decreased fetal weight, increased placental weight, reduced fetal-to-placental weight ratio, and abnormal placental remodeling. CircRNA sequencing of GD 13.5 placentas identified mmu_circ_0000506, referred to as circKAT6B, as a conserved TCS-responsive circRNA. TCS increased circKAT6B and TCF12 expression while suppressing miR-204-5p in placental tissues and HTR-8/SVneo trophoblast cells. Functionally, TCS impaired trophoblast migration, invasion, and endothelial tube-supporting activity. Mechanistic assays showed that circKAT6B was predominantly cytoplasmic, resistant to RNase R digestion, and enriched in AGO2-containing complexes. Dual-luciferase reporter assays confirmed sequence-specific interactions between circKAT6B and miR-204-5p, as well as between miR-204-5p and TCF12. Rescue experiments further demonstrated that miR-204-5p restoration or TCF12 knockdown partially reversed circKAT6B-associated trophoblast dysfunction under TCS exposure. In addition, promoter reporter assays suggested that TCF12 transcriptionally activates PCDH9, a candidate adhesion-related downstream effector. Collectively, these findings indicate that TCS disrupts early pregnancy and placental development, and that the circKAT6B/miR-204-5p/TCF12-PCDH9 axis contributes, at least in part, to TCS-induced trophoblast dysfunction.