Stathmin 1 plays a role in endometrial decidualisation by regulating hypoxia inducible factor-1α and vascular endothelial growth factor during embryo implantation
Jinhai Gou A , Jia Jia A , Juntao Feng A , Xia Zhao A B , Tao Yi B , Tao Cui A and Zhengyu Li A B CA Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, PR China.
B Sichuan Key Laboratory of Gynecologic Oncology, West China Second University Hospital, Sichuan University, No.20, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, PR China.
C Corresponding author. Email: zhengyuli@scu.edu.cn
Reproduction, Fertility and Development 29(8) 1530-1537 https://doi.org/10.1071/RD15539
Submitted: 20 December 2015 Accepted: 21 June 2016 Published: 26 July 2016
Abstract
The aim of the present study was to explore the potential mechanism underlying stathmin 1 (Stmn1) regulation of embryo implantation, as a continuation of previous proteomic research. Adult healthy female mice were mated naturally with fertile males. Murine uterine tissue was collected during the peri-implantation period. Local expression of Stmn1 during embryo implantation was detected by immunohistochemistry (IHC), which showed that Stmn1 was extensively expressed in endometrial glandular epithelium, vascular endothelium, luminal epithelium and the underlying stromal cells at the implantation site on Day 5. The role of Stmn1 during embryo implantation was evaluated by transient knockdown of Stmn1 in vivo using short interference (si) RNA, and some associated factors including Akt, phosphorylated (p-) Akt, hypoxia-inducible factor (HIF)-1α, prolactin (PRL), insulin-like growth factor binding protein (IGFBP) 1 and vascular endothelial growth factor (VEGF) were examined by western blotting analysis and ELISA. The number of embryos implanted after Stmn1-siRNA infusion into the lumen of one uterine horn was lower than that with normal pregnancies (2.2 ± 1.5 vs 8.6 ± 0.5 respectively; P < 0.05). The expression of VEGF, HIF-1α, p-Akt and the decidualisation biomarkers PRL and IGFBP 1 was upregulated at the implantation site on Day 5, but downregulated after Stmn1-siRNA infusion. These findings suggest that during embryo implantation, knockdown of Stmn1 suppresses decidualisation by inhibiting the expression of p-Akt, HIF-1α and VEGF, thus leading to impaired embryo implantation. These findings provide clues for understanding the complicated process of embryo implantation and the potential role of Stmn1 during embryo implantation.
Additional keyword: angiogenesis.
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