The elevated YTHDC1 affects trophoblastic function and induces preterm birth in ART conception via augmenting RPL37 translation

Here, it is shown that YTHDC1 was significantly increased in the human preterm placenta after ART and the murine preterm placenta after E2 exposure. Overexpression of YTHDC1 significantly promoted the proliferation, migration, and invasion of trophoblast cells, but inhibited their apoptosis. Knockdown or knockout of YTHDC1 played an opposite effect. Mechanistically, E2 promoted YTHDC1 expression through retinoid X receptor alpha (RXRA) upregulation. YTHDC1 could activate WNT and JAK/STAT signaling pathways in the human trophoblast cells. Meanwhile, YTHDC1 could fine-tone the translation of ribosomal protein L37 (RPL37) in a m6A-dependent manner, which then influence the cellular total protein synthesis. Importantly, administration of siRNA targeting YTHDC1 effectively delays preterm birth in vivo. Collectively, these findings uncover the epigenetic mechanism underlying ART preterm birth and provide a potential target for therapeutic intervention.