TET1-mediated DNA demethylation suppresses migration of goat placental trophoblast cells.

The placenta is essential for supporting fetal growth by delivering nutrients and removing waste products. Its development hinges on precise epigenetic regulation, yet the role of Ten-eleven translocation 1 (TET1) in ruminant trophoblast biology remains unclear. Here, we show that TET1 acts as a suppressor of goat placental trophoblast cells (GTCs) migration. Using immortalized GTCs, we induced TET1 overexpression via 20 ng/μL doxycycline (Dox) and achieved knockdown through shRNA (piLenti-shTET1-GFP-a). Overexpression of TET1 markedly reduced GTCs migration and viability, whereas knockdown enhanced migration, with these effects reversible by restoring TET1 expression using Dox. Mechanistically, TET1 influenced chemical changes to DNA that control gene activity, decreasing DNA methylation mark (5mC) while increasing hydroxymethylation mark (5hmC). Conversely, TET1 knockdown had the opposite effect on these marks. Our results establish TET1 as a key suppressor of goat trophoblast cell migration via DNA modifications, providing novel insights into placental development and potential strategies for improving reproductive efficiency in livestock.