Enhanced HOXA10 sumoylation inhibits embryo implantation in women with recurrent implantation failure.

HOXA10 has emerged as an important molecular marker of endometrial receptivity. Recurrent implantation failure (RIF) after fertilization-embryo transplantation (IVF-ET) treatment is associated with impaired endometrial receptivity, but the exact underlying mechanism of this phenomenon remains elusive. Here we found that HOXA10 was modified by small ubiquitin like-modifier 1 (SUMO1) at the evolutionarily conserved lysine 164 residue. Sumoylation inhibited HOXA10 protein stability and transcriptional activity without affecting its subcellular localization. SUMO1-modified HOXA10 expression was decreased in estradiol- and progesterone-treated Ishikawa cells. Sumoylation inhibited the accelerant role of HOXA10 in BeWo spheroid and mouse embryo attachment to Ishikawa cells. Importantly, aberrantly high SUMO1-HOXA10 expression was detected in mid-secretory endometria of women with RIF compared with that of the control fertile women. Together, our results suggest that HOXA10 sumoylation impairs the process of embryo implantation and takes part in the development of RIF.