Decreased Stathmin-1 Expression Inhibits Trophoblast Proliferation and Invasion and Is Associated with Recurrent Miscarriage

作者：Tian, Fu-Ju; Qin, Chuan-Mei; Li, Xiao-Cui; Wu, Fan; Liu, Xiao-Rui; Xu, Wang-Ming; Lin, Yi^*

来源：American Journal Of Pathology, 2015, 185(10): 2709-2721.

DOI：10.1016/j.ajpath.2015.06.010

• MATERNAL-FETAL INTERFACE
• HUMAN DECIDUAL MACROPHAGES
• ACTIVATED PROTEIN-KINASE
• IN-VITRO
• SPONTANEOUS-ABORTION
• CELLS
• DIFFERENTIATION
• MIGRATION
• IMPLANTATION
• PREGNANCY

Fetal trophoblasts invade endometrium and establish a complex interaction with the maternal microenvironment during early pregnancy. However, the molecular mechanisms regulating trophoblast migration and invasion at the maternal fetal interface remain poorly understood. Immunohistochemistry and immunoblotting have shown that stathmin-1 (STMN1) was down-regulated significantly in placental villi tissue and trophoblasts from patients with recurrent miscarriage. In vitro, overexpression of STMN1 promoted human trophoblast proliferation, migration, and invasion, whereas knockdown of STMN1 inhibited these processes. In addition, knockdown of STMN1 down-regulated N-cadherin and upregulated E-cadherin in trophoblasts, whereas E-cadherin was up-regulated and N-cadherin was downregulated in recurrent miscarriage villi tissue. Knockdown of STMN1 attenuated cytoplasmic nuclear translocation of beta-catenin and in turn down-regulated trophoblast matrix metalloproteases. Furthermore, tumor necrosis factor-alpha (INF-alpha) down-regulated STMN1 expression, and serum TNF-alpha expression correlated inversely with trophoblast STMN1 levels. Interestingly, M1 macrophage-derived TNF-alpha reduced trophoblast migration and invasion, and an anti-INF-alpha antibody reversed this effect. Collectively, this study indicated that STMN1 may play a key role in regulating trophoblast invasion, and that impaired STMN1 expression may lead to abnormal trophoblast invasion and result in recurrent miscarriage.

• 出版日期2015-10
• 单位武汉大学; 上海交通大学