Human endogenous retrovirus-FRD envelope protein (syncytin 2) expression in normal and trisomy 21-affected placenta

André Malassiné,Karen Handschuh,Jean-Louis Frendo,Danièle Evain-Brion,Sandra Blaise,Thierry Heidmann,Vassilis Tsatsaris,Pascale Gerbaud

doi:10.1186/1742-4690-5-6

Abstract

Human trophoblast expresses two fusogenic retroviral envelope proteins, the widely studied syncytin 1, encoded by HERV-W and the recently characterized syncytin 2 encoded by HERV-FRD. Here we studied syncytin 2 in normal and Trisomy 21-affected placenta associated with abnormal trophoblast differentiation. Syncytin 2 immunolocalization was restricted throughout normal pregnancy to some villous cytotrophoblastic cells (CT). During the second trimester of pregnancy, syncytin 2 was immunolocalized in some cuboidal CT in T21 placentas, whereas in normal placentas it was observed in flat CT, extending into their cytoplasmic processes. In vitro, CT isolated from normal placenta fuse and differentiate into syncytiotrophoblast. At the same time, syncytin 2 transcript levels decreased significantly with syncytiotrophoblast formation. In contrast, CT isolated from T21-affected placentas fused and differentiated poorly and no variation in syncytin 2 transcript levels was observed. Syncytin 2 expression illustrates the abnormal trophoblast differentiation observed in placenta of fetal T21-affected pregnancies.

Highlights

Human endogenous retroviruses (HERV) comprise approximately 8% of the human genome [1,2]
In first trimester placenta (Fig. 2A–B), syncytin 2 was only detected at the level of the cytotrophoblastic cells, which form a continuous single layer of cuboidal cells beneath the syncytiotrophoblast
In second trimester placenta (Fig. 2C–D), syncytin 2 immunostaining was present: 1/in the cytoplasm of cytotrophoblastic cells; 2/ in their thin elongated cytoplasmic processes coming into contact with the syncytiotrophoblast and covering the villus basal lamina

Summary

Introduction

Human endogenous retroviruses (HERV) comprise approximately 8% of the human genome [1,2]. A systematic search for non-defective endogenous retrovirus envelope protein genes has led to the identification of 16 genes [3]. Two can induce cell-cell fusion when expressed in different cells and are highly and expressed in the human placenta [4,5,6]. The products of these two genes are glycoproteins named HERV-W Env glycoprotein (syncytin 1) and HERV-FRD Env glycoprotein (syncytin 2). The trophoblast differentiates along two major pathways both critical for normal placental function [7].

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