Skp2 Deteriorates the Uterine Receptivity by Interacting with HOXA10 and Promoting its Degradation

Receptive endometrium plays a core role in successful embryo implantation, and about one-third of repeated embryo implantation failures are attributed to endometrial receptive defects. S-phase kinase-associated protein 2 (SKP2), a member of the F-box protein family, plays an important role in many cellular processes, including cell proliferation and apoptosis. However, its role in endometrial receptivity is still unclear. Here, we identified SKP2 was obviously upregulated in the patients with infertility. Functional study showed that SKP2 overexpression inhibited endometrial epithelial cell (EEC) proliferation, whereas SKP2 knockdown promoted the proliferation of EECs. In addition, the overexpression of SKP2 also repressed adhesion rate of embryonic cells to EECs. In vivo studies further suggested that the upregulation of SKP2 obviously suppressed endometrium receptivity formation and embryo implantation potential. Mechanistical study clarified that SKP2 directly interacted with HOXA10 and decreased protein stability through promoting the ubiquitin-mediated proteasome degradation of HOXA10. In conclusion, the current study documented that the high expression of SKP2 deteriorates endometrial receptivity formation by decreasing the HOXA10 expression and suggested that SKP2 may be defined as a marker of endometrial receptivity, and as a target for the diagnosis and treatment of infertility.