Effect of the p53–tristetraprolin–stathmin-1 pathway on trophoblasts at maternal–fetal interface

PROBLEM To reveal the effect of p53-tristetraprolin-stathmin-1 signaling on trophoblasts and recurrent spontaneous abortion (RSA). METHOD OF STUDY Stathmin-1 (STMN1), p53, and tristetraprolin (TTP) expression in paraffin-embedded villus tissue was determined using immunohistochemistry. HTR-8/SVneo cells were treated with doxorubicin to activate p53; STMN1 and TTP levels were detected by quantitative reverse transcription-PCR and western blotting. Western blotting and immunofluorescence were used to investigate STMN1 expression after TTP overexpression or knockdown in HTR-8 cells. RESULTS STMN1 was downregulated and p53 was upregulated in the villus tissue from patients with RSA. Doxorubicin decreased STMN1 expression but enhanced TTP expression in HTR-8 cells. In vitro, TTP overexpression inhibited STMN1 production; TTP knockdown promoted it. TTP downregulated STMN1 expression in trophoblasts by directly binding its 3' untranslated region. CONCLUSIONS TTP modulates trophoblast function and interacts with STMN1 and p53, and is related to pregnancy outcomes.