Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia

Development of placentation and successful pregnancy depend on co-ordinated interactions between the maternal decidua. and myometrium, and the invasiv e properties of the fetal trophoblast. Syncytin, a protein encoded by the e nvelope gene of a recently identified human endogenous defective retrovirus , HERV-W, is highly expressed in placental tissue. Previously, we have show n that the major site of syncytin expression is the placental syncytiotroph oblast, a fused multinuclear syncytium. originating from cytotrophoblast ce lls. Here we present the first evidence that in pre-eclampsia, syncytin gen e expression levels are dramatically reduced. Additionally, immunohistochem ical examination of normal placentae and placentae from women with pre-ecla mpsia reveals that the syncytin protein in placental tissue from women with pre-eclampsia is localized improperly to the apical syncytiotrophoblast mi crovillous membrane as opposed to its normal location on the basal syncytio trophoblast cytoplasmic membrane. Our previous results suggest that syncyti n may mediate placental cytotrophoblast fusion in vivo and may play an impo rtant role in human placental morphogenesis. The present study suggests tha t altered expression of the syncytin gene, and altered cellular location of its protein product, may contribute to the aetiology of pre-eclampsia. (C) 2001 Harcourt Publishers Ltd.