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Mol. Hum. Reprod. Advance Access published online on January 16, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gal111
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Increased cystatin C expression in the pre-eclamptic placenta

Karl Kristensen1, I. Larsson and S.R. Hansson

Department of Obstetrics and Gynaecology, University Hospital, Lund, Sweden

1 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, University Hospital, Lund University, SE-221 85 Lund, Sweden. Tel: +46 46 172520; Fax: +46 46 157868; E-mail: karl.kristensen{at}med.lu.se

Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concentration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue samples from the central part of the placenta from 13 normal and 22 pre-eclamptic pregnancies were included. We used real-time polymerase chain reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and immunohistochemistry and Western blotting for protein expression analysis. RT-PCR showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than in normal pregnancy, with the highest expression in cases with severe pre-eclampsia. In situ hybridization revealed a distinct pattern of high expression in the extravillous trophoblast cells of the basal plate and low expression in the syncytiotrophoblast covering villi. The cystatin C protein distribution matched the mRNA expression pattern. Western blot analysis revealed an increased protein expression in cases with severe pre-eclampsia and confirmed the presence of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA in the extravillous trophoblast cells of the basal plate suggests a role for cystatin C in the regulation of proteases in placentation. Placental expression and secretion of cystatin C could contribute to the elevated maternal plasma levels seen in pre-eclampsia.

Key Words: amniotic fluid/placentation/proteinase inhibitor/trophoblast


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