Skp2 Deteriorates the Uterine Receptivity by Interacting with HOXA10 and Promoting its Degradation
- PDF / 6,954,554 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 85 Downloads / 145 Views
INFERTILITY: ORIGINAL ARTICLE
Skp2 Deteriorates the Uterine Receptivity by Interacting with HOXA10 and Promoting its Degradation Keping Han 1 & Qi Zhou 2 Received: 18 August 2020 / Accepted: 19 October 2020 # Society for Reproductive Investigation 2020
Abstract 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. Keywords SKP2 . Endometrial receptivity . HOXA10 . Ubiquitination
Introduction The receptive endometrium is a precondition for successful embryo implantation. In the presence of embryo and in response to hormone, the endometrial luminal epithelium undergoes hyperproliferation, decidualization, and increased vascularization [1, 2]. These physiologically functional changes are also related to the expression change of the gene related to transcriptional regulation [3, 4]. Moreover, the expression of these genes is abnormal changed in the endometrium of infertile women and those experiencing recurrent implantation failure [5, 6]. Despite recent advances in the understanding of uterine receptivity, the underlying
* Qi Zhou [email protected] 1
Department of Obstetrics and Gynecology, The People’s Hospital of Yuyao, Yuyao 315400, Zhejiang Province, China
2
Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, People’s Republic of China
mechanisms of poor endometrial receptivity in infertility and implantation failure remain poorly understood. The S-phase kinase-associated protein 2 (SKP2) F-box protein is the substrate recruiting component of the Skp1-Cullin 1-F-box type of E3 ubiquitin-ligase complexes. This family of E3 ligase belongs to the ubiquitin-proteasome system that controls the function of various cell [7, 8].
Data Loading...
