Severe feto-placental abnormalities precede the onset of hypertension and proteinuria in a mouse model of preeclampsia

Anuja DOKRAS; Darren S HOFFMANN; Joshua S EASTVOLD; Martha F KIENZLE; Lynn M GRUMAN; Patricia A KIRBY; Robert M WEISS; Robin L DAVISSON

doi:10.1095/biolreprod.106.053603

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Severe feto-placental abnormalities precede the onset of hypertension and proteinuria in a mouse model of preeclampsia

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Severe feto-placental abnormalities precede the onset of hypertension and proteinuria in a mouse model of preeclampsia

Anuja DOKRAS, Darren S HOFFMANN, Joshua S EASTVOLD, Martha F KIENZLE, Lynn M GRUMAN, Patricia A KIRBY, Robert M WEISS and Robin L DAVISSON

Biology of reproduction, Vol.75(6), pp.899-907

2006

DOI: 10.1095/biolreprod.106.053603

PMID: 16957025

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Abstract

Preeclampsia is a prevalent and potentially devastating disorder of pregnancy. Characterized by a sudden spike in blood pressure and urinary protein levels, it is associated with significant obstetric complications. BPH/5 is an inbred mouse model of preeclampsia with borderline hypertension before pregnancy. BPH/5 mice develop hypertension, proteinuria, and endothelial dysfunction during late gestation (after E14.5). We hypothesized that BPH/5 mice might exhibit early feto-placental abnormalities before the onset of maternal disease. All placental cell lineages were present in BPH/5 mice. However, the fetal and placental weights were reduced, with abnormalities in all the placental zones observed starting early in gestation (E9.5-E12.5). The fractional area occupied by the junctional zone was significantly reduced at all gestational timepoints. Markedly fewer CDKN1C-stained trophoblasts were seen invading the proximal decidual zone, and this was accompanied by reductions in Cdkn1c gene expression. Trophoblast giant cell morphology and cytokeratin staining were not altered, although the mRNA levels of several giant cell-specific markers were significantly downregulated. The labyrinth layer displayed decreased branching morphogenesis of endothelial cells, with electron microscopy evidence of attenuated trophoblast layers. The maternal decidual arteries showed increased wall-to-lumen ratios with persistence of actin-positive smooth muscle cells. These changes translated into dramatically increased vascular resistance in the uterine arteries, as measured by pulse-wave Doppler. Collectively, these results support the hypothesis that defects at the maternal-fetal interface are primary causal events in preeclampsia, and further suggest the BPH/5 model is important for investigations of the underlying pathogenic mechanisms in preeclampsia.

Fundamental and applied biological sciences. Psychology

Cardiology. Vascular system

Arterial hypertension. Arterial hypotension

Vertebrates: reproduction

Embryology: invertebrates and vertebrates. Teratology

Fetal membranes

Biological and medical sciences

Medical sciences

General aspects. Development. Fetal membranes

Blood and lymphatic vessels

Experimental diseases

Details

Title: Subtitle: Severe feto-placental abnormalities precede the onset of hypertension and proteinuria in a mouse model of preeclampsia
Creators: Anuja DOKRAS - Department of Obstetrics and Gynecology, Roy j. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
Darren S HOFFMANN - Department of Anatomy and Cell Biology, Roy j. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
Joshua S EASTVOLD - Department of Anatomy and Cell Biology, Roy j. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
Martha F KIENZLE - Department of Anatomy and Cell Biology, Roy j. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
Lynn M GRUMAN - Department of Anatomy and Cell Biology, Roy j. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
Patricia A KIRBY - Department of Pathology, Roy j. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
Robert M WEISS - Internal Medicine and Veterans Affairs, Roy j. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
Robin L DAVISSON - Department of Anatomy and Cell Biology, Roy j. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, United States
Resource Type: Journal article
Publication Details: Biology of reproduction, Vol.75(6), pp.899-907
Publisher: Society for the Study of Reproduction; Madison, WI
DOI: 10.1095/biolreprod.106.053603
PMID: 16957025
ISSN: 0006-3363
eISSN: 1529-7268
Language: English
Date published: 2006
Academic Unit: Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Pathology; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984025324102771

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