Genome-wide expression profiling of placentas in the p57Kip2 model of pre-eclampsia
Open accessAbstract
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 p57(Kip2) 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 p57(Kip2) develop pre-eclampsia when carrying fetuses that lack p57(Kip2) expression. This demonstrates that either the fetus or the placenta causes the disease. Here, taking advantage of the unique genetics of the p57(Kip2) mouse, we have used full genome expression profiling to define the placental aspect of the p57(Kip2) 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 p57(Kip2) 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 p57(Kip2) mutant mice. Our studies suggest a role for environmental factors in the p57(Kip2) pre-eclampsia phenotype and have identified several candidates for pre-eclampsia predisposition in this model, including known regulators of blood pressure, inflammation and apoptosis.
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A recent study of placental gene expression in a mouse model of PE showed hepcidin expression increased by a greater factor than any other gene save one, consistent with major changes in iron liganding and metabolism underpinning PE.
“a recent study by Knox and colleagues of placental gene expression in a mouse model of PE showed that hepcidin expression increased by a greater factor than that of any other gene save one [536], consistent with the view that major changes in the regulation of iron liganding and metabolism underpin PE.”
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- Authors
- Knox, K. S., & Baker, J. C.
- Affiliations
- Stanford University (US)
- ORCID
- Baker, J.C.
- Venue
- MHR: Basic science of reproductive medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-02-08
- Volume
- 13
- Issue
- 4
- Pages
- 251-263
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- OpenAlex
- W2104574464
- Cited by
- 33
- References
- 71
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2013: 5 · 2012: 4
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Molecular Human Reproduction (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Funders
- March of Dimes Foundation
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
- Keywords
- preeclampsia, p57KIP2, placenta, placental gene expression, placental development, uteroplacental blood flow, proteinuria, premature labour, environmental factors, inflammation, apoptosis, mouse model
- MeSH terms
- Animals, Blood Pressure, Disease Models, Animal, Female, Genotype, Hormones, Inflammation, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Placenta, Pre-Eclampsia, Pregnancy, RNA, Messenger, Time Factors, Gene Expression, Apoptosis, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor A, Cyclin-Dependent Kinase Inhibitor p57, Mice
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