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Int J Clin Exp Pathol 2011;4(8):765-774

Original Article
EPO Improves the proliferation and inhibits apoptosis of trophoblast and decidual
stromal cells through activating STAT-5 and inactivating p38 signal in human early

Yu Qing Ji, Yu Quan Zhang, Ming Qing Li, Mei Rong Du, Wei Wei Wei, Da Jin Li

Department of Gynecology & Obstetrics, Nantong University Medical College, Nantong 226001, China; Laboratory for Reproductive
Immunology, Hospital & Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai 200011, China;
Department of Gynecology & Obstetrics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital,
Shanghai 200233, China

Received September 21, 2011; accepted November 2, 2011; Epub November 3, 2011; Published November 30, 2011

Abstract: The erythropoietin (EPO) belongs to the family of angiogenic factors, which is regulated by Hypoxia-inducible factor- 1α (HIF-1α). As
known, EPO are expressed in human villi and decidua, but the function is not clear. In this study, we investigated the expression and roles of
HIF-1α, EPO and its receptor (EPOR) in the biological functions of trophoblast and decidual stromal cell (DSC) in human early pregnancy. The
expression of EPO, EPOR and HIF-1α was evaluated in the villi and deciduas by RT-PCR and immunohistochemistry. Thereafter, we silenced
HIF-1α expression in HTR-8/SVneo cell line and decidual stromal cells (DSCs). The effects of EPO on the proliferation and apoptosis of
trophoblasts and DSCs, and activation of signal molecules were investigated by BrdU proliferation assay, flow cytometry and western blot,
respectively. We have observed that the HIF-1α silence results in the lower expression of EPO in trophoblasts and DSCs. The anti-EPO
neutralizing antibody can inactivate the phosphorylation of STAT5 and activate p38 of these cells in a dosage-dependent manner. Furthermore,
the expressions of EPO, EPOR and HIF-1α in the villi and decidua from the unexplained miscarriage were significantly lower than that of the
normal early pregnancy. This study suggests that HIF-1α may regulates the expression of EPO, which plays a favorable regulatory role in the
proliferation and survival of human first-trimester trophoblast cells and DSCs via inactivating p38 and activating STAT5 in an autocrine manner,
while the inadequate EPO expression at maternal-fetal interface may lead to pregnancy wastage in humans.

Keywords: EPO, HIF-1, trophoblast cell, decidual stromal cell, STAT5, p38

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Address all correspondence to:
Dr. Da Jin Li
Laboratory for Reproductive Immunology
Hospital & Institute of Obstetrics and Gynecology
IBS, Fudan University Shanghai Medical College
Shanghai 200011, China.
Tel: 86-21-63457331; Fax: 86-21-63457331
E-mail: djli@shmu.edu.cn;

Dr. Yu Quan Zhang
Department of Gynecology & Obstetrics
Nantong University Medical College
Nantong 226001, China.
Tel: 86-513-85935566; Fax: 86-513-85935566
E-mail: jsnt_zhangyuquan@tom.com.cn