Spatiotemporal expression of SERPINE2 in the human placenta and its role in extravillous trophoblast migration and invasion

Schu-Rern Chern,Sheng-Hsiang Li,Chien-Ling Chiu,Hsiao-Ho Chang,Edmund I Tsuen Chen,Chih-Ping Chen

doi:10.1186/1477-7827-9-106

Abstract

BackgroundSERPINE2, one of the potent serpins belonging to the plasminogen activator (PA) system, is involved in the tissue remodeling. We previously demonstrated the expression patterns of Serpine2 in the mouse placenta and uterus, indicating that Serpine2 is a major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation. In this study, we further investigated the expression pattern of SERPINE2 in the human placenta and explored possible functional roles of SERPINE2 in regulating trophoblast activity.MethodsPlacental tissues from various trimesters were collected for real-time reverse-transcription polymerase chain reaction quantification. Immunohistochemical staining was performed in placental tissues to assure localization of SERPINE2. SERPINE2 small interfering (si) RNA was applied to suppress its expression in villous explants and extravillous trophoblast-like 3A cells. Subsequent experiments to evaluate SERPINE2 levels, villous outgrowth, trophoblast invasion, and tube formation were performed.ResultsSERPINE2 messenger RNA was detected in the human placenta during pregnancy with the highest levels in the third trimester. The SERPINE2 protein was present in villous syncytiotrophoblasts and trophoblasts of chorionic villi for anti-SERPINE2 immunostaining. Extravillous trophoblasts in the chorionic plate and basal plate confronting the invasive face of anchoring villi were also positive. In most decidual cells, SERPINE2 was observed in the cytoplasm. In addition, fibrinoid deposit was weakly immunoreactive. Introduction of SERPINE2 siRNA into villous explants and trophoblast cells led to significantly reduced villous outgrowth, and trophoblastic migration and invasion. Moreover, capillary-like network formation of 3A cells in Matrigel was greatly attenuated by SERPINE2 siRNA and SERPINE2 antiserum.ConclusionsThese data identify the temporal and spatial SERPINE2 distribution in the human placenta and suggest its possible role in modulating tissue remodeling of extravillous trophoblasts in the placenta during pregnancy.

Highlights

SERPINE2, one of the potent serpins belonging to the plasminogen activator (PA) system, is involved in the tissue remodeling
Spatiotemporal expression of SERPINE2 in the human placenta We analyzed the expression of SERPINE2 in human placentas from various trimesters (n = 5, 4, and 10 for the first, second, and third trimesters, respectively) at the messenger RNA (mRNA) level by real-time RT-PCR
SERPINE2 protein expression was visible in extravillous trophoblast cells and decidual cells of the chorionic plate (Figure 1B)

Summary

Introduction

SERPINE2, one of the potent serpins belonging to the plasminogen activator (PA) system, is involved in the tissue remodeling. We previously demonstrated the expression patterns of Serpine in the mouse placenta and uterus, indicating that Serpine is a major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation. We further investigated the expression pattern of SERPINE2 in the human placenta and explored possible functional roles of SERPINE2 in regulating trophoblast activity. It was shown to be a potent inhibitor of the urokinase-plasminogen activator (uPA), tissue-type PA (tPA), thrombin, trypsin, factor XIa, and prostasin [1,2,3,4,5]. Expression levels of SERPINE2 in the monkey endometrium and placenta during early pregnancy were below the level of detection [10]. Serpine messenger RNA (mRNA) expression was only detected in endometrial stromal cells of the uterus, at the time of implantation [11]

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