Evidence for Transcriptional Activity in the Syncytiotrophoblast of the Human Placenta

Ellery, P.M.; Cindrova-Davies, T.; Jauniaux, E.; Ferguson-Smith, A.C.; Burton, G.J.

doi:10.1016/j.placenta.2009.01.002

« Previous Next »Placenta
Volume 30, Issue 4 , Pages 329-334, April 2009

Evidence for Transcriptional Activity in the Syncytiotrophoblast of the Human Placenta

P.M. Ellery
- Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
T. Cindrova-Davies
- Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
E. Jauniaux
- Academic Department of Obstetrics and Gynaecology, Royal Free and University College, London, UK
A.C. Ferguson-Smith
- Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
G.J. Burton
- Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
- Corresponding author. Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. Tel.: +44 (0)1223 333856; fax: +44 (0)1223 333840.

Accepted 9 January 2009. published online 12 February 2009.

Abstract

The aim was to test for evidence of transcriptional activity within the nuclei of the syncytiotrophoblast of the human placenta. The syncytiotrophoblast forms the epithelial covering of the villous tree, and is a multinucleated, terminally-differentiated syncytium generated through fusion of the underlying progenitor cytotrophoblast cells. Its nuclei are heterogeneous with respect to chromatin condensation, and previous functional studies of 3H-uridine uptake in vitro have indicated that they are transcriptionally inactive. This observation is surprising given the key roles this tissue plays in active transport, hormone synthesis and metabolic regulation, and has widespread implications for trophoblast physiology and pathophysiology. We used three different approaches to look for evidence of transcriptional activity. First, immunofluorescence staining was performed on paraffin-embedded early pregnancy and term placental villi, using an antibody directed specifically against the actively transcribing form of RNA polymerase II. Second, a nucleoside incorporation assay was applied to placental villi maintained in short-term culture, with and without the transcription blocker α-amanitin. Third, histone modifications associated with active chromatin were identified by immunohistochemistry and immunofluorescence. Each of these methods showed transcription to be occurring in a proportion of syncytiotrophoblast nuclei, with qualitative evidence for transcription being more abundant in the first trimester than at term. These findings correlated with electron microscopical observations of prominent nucleoli within the nuclei, particularly during early pregnancy, signifying transcription of ribosomal RNA. Contrary to previous findings, these results confirm that a proportion of syncytiotrophoblast nuclei actively produce mRNA transcripts.

Keywords: Placenta, Syncytiotrophoblast, Syncytial knots, Transcription, RNA polymerase II