Decreased stathmin-1 expression inhibits trophoblast proliferation and invasion and is associated with recurrent miscarriage.
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 up-regulated E-cadherin in trophoblasts, whereas E-cadherin was up-regulated and N-cadherin was down-regulated in recurrent miscarriage villi tissue. Knockdown of STMN1 attenuated cytoplasmic-nuclear translocation of β-catenin and in turn down-regulated trophoblast matrix metalloproteases. Furthermore, tumor necrosis factor-α (TNF-α) down-regulated STMN1 expression, and serum TNF-α expression correlated inversely with trophoblast STMN1 levels. Interestingly, M1 macrophage-derived TNF-α reduced trophoblast migration and invasion, and an anti-TNF-α 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.
International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Fu-Ju
FJ
Tian
International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chuan-Mei
CM
Qin
International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiao-Cui
XC
Li
International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Fan
F
Wu
International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiao-Rui
XR
Liu
Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: wangmingxu118@163.com.
Wang-Ming
WM
Xu
International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Embryo-Fetal Original Adult Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yilinonline@126.com.
Yi
Y
Lin
D000026:Abortion, Habitual / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002824:Chorionic Villi / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology; D050777:Stathmin / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D015820:Cadherins; C493995:STMN1 protein, human; D050777:Stathmin; D014409:Tumor Necrosis Factor-alpha