Sera from Preeclampsia Patients Elicit Symptoms of Human Disease in Mice and Provide a Basis for an in Vitro Predictive Assay
2010 (English)In: AMERICAN JOURNAL OF PATHOLOGY, ISSN 0002-9440, Vol. 177, no 5, 2387-2398 p.Article in journal (Refereed) Published
Early diagnosis and treatment of preeclampsia would significantly reduce maternal and fetal morbidity and mortality. However, its etiology and prediction have remained elusive. Based on the hypothesis that sera from patients with preeclampsia could function as a "blueprint" of causative factors, we describe a serum-based pregnancy-specific mouse model that closely mirrors the human condition as well as an in vitro predictive assay. We show that a single administration of human preeclampsia serum in pregnant IL-10(-/-) mice induced the full spectrum of preeclampsia-like symptoms, caused hypoxic injury in uteroplacental tissues, and elevated soluble fins-like tyrosine kinase 1 and soluble endoglin, markers thought to be related to the disease. The same serum sample(s) induced a partial preeclampsia phenotype in wild-type mice. Importantly, preeclampsia serum disrupted cross talk between trophoblasts and endothelial cells in an in vitro model of endovascular activity. Disruption of endovascular activity could be documented in serum samples as early as 12 to 14 weeks of gestation from patients who subsequently developed preeclampsia. These results indicate that preeclampsia patient sera can be used to understand the pregnancy-specific disease pathology in mice and can predict the disorder.
Place, publisher, year, edition, pages
American Society for Investigative Pathology (ASIP) , 2010. Vol. 177, no 5, 2387-2398 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-62755DOI: 10.2353/ajpath.2010.100475ISI: 000284182900026OAI: oai:DiVA.org:liu-62755DiVA: diva2:374198