Annexin A2 acts as an adherent molecule under the regulation of steroids during embryo implantation.

We previously showed that annexin A2 was transiently expressed at the embryo-uterine luminal epithelium interface during the window of implantation, and was involved in mouse embryo implantation. At the same time, annexin A2 was reported to be upregulated in human receptive endometrium, which was critical for embryo attachment as an intracellular molecule. Here, we identified annexin A2 as a membrane bound molecule on human endometrial epithelial cells and trophoblast cells, and the outer surface membrane bound annexin A2 was involved in human embryo attachment. In addition, physiological levels of estrogen and progesterone increased the expression of overall annexin A2 as well as that in the extracellular surface membrane protein fraction in human endometrial cells. Furthermore, p11 (or S100A10, a member of the S100 EF-hand family protein, molecular weight 11 kDa) was involved in the translocation of annexin A2 to the outer surface membrane of endometrial epithelial cells without affecting its overall expression. Finally, the surface relocation of annexin A2 was also dependent on cell-cell contact and calcium binding. A better understanding of the function and regulation of annexin A2 in human endometrium may help us to identify a potential therapeutic target for subfertile and infertile patients.