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Mol. Hum. Reprod. Advance Access originally published online on February 8, 2007
Molecular Human Reproduction 2007 13(4):251-263; doi:10.1093/molehr/gal116
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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
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Genome-wide expression profiling of placentas in the p57Kip2 model of pre-eclampsia

K.S. Knox and J.C. Baker1

Genetics Department, Standford University, Stanford, CA, USA

1 To whom correspondence should be addressed at: Genetics Department, Stanford University, Stanford, CA 94062, USA. E-mail: jbaker{at}stanford.edu

Pre-eclampsia affects 6–10% of pregnancies and is one of the primary causes of premature birth. It is widely accepted that inappropriate placental development, combined with environmental factors, plays a major role in disease pathogenesis. The p57Kip2 mouse is the only mouse model of pre-eclampsia that recapitulates the full spectrum of symptoms of the human disease, including placental abnormalities, hypertension, proteinuria and premature labour. In addition, pregnant females expressing wild-type levels of p57Kip2 develop pre-eclampsia when carrying fetuses that lack p57Kip2 expression. This demonstrates that either the fetus or the placenta causes the disease. Here, taking advantage of the unique genetics of the p57Kip2 mouse, we have used full genome expression profiling to define the placental aspect of the p57Kip2 phenotype at a molecular level and to conduct an unbiased search for factors involved in pre-eclampsia pathogenesis. During this analysis, we found that although mutant embryos demonstrate altered placental architecture and have histological changes indicative of reduced utero-placental blood flow, the p57Kip2 pregnant females do not demonstrate hypertension or renal pathology. This suggests a model in which placental abnormalities cause pre-eclampsia only given other environmental variables. On the basis of this model, we expect that misregulation of molecular factors, while not able to cause a full spectrum of disease symptoms in this context, still occurs in these p57Kip2 mutant mice. Our studies suggest a role for environmental factors in the p57Kip2 pre-eclampsia phenotype and have identified several candidates for pre-eclampsia predisposition in this model, including known regulators of blood pressure, inflammation and apoptosis.

Key words: gene expression profiling/mouse model of human disease/p57Kip2/placenta/pre-eclampsia


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