Sera from preeclampsia patients elicit symptoms of human disease in mice and provide a basis for an in vitro predictive assay.
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 fms-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.
Kalkunte
Satyan
S
Department of Pediatrics, Women and Infants Hospital-Warren Alpert Medical School, Lifespan Center for International Health Research, Brown University, 101 Dudley St, Providence, RI 02905, USA.
Boij
Roland
R
Norris
Wendy
W
Friedman
Jennifer
J
Lai
Zhongbin
Z
Kurtis
Jonathan
J
Lim
Kee-Hak
KH
Padbury
James F
JF
Matthiesen
Leif
L
Sharma
Surendra
S
D000818:Animals; D001681:Biological Assay / Q000379:methods*; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D006801:Humans; D000860:Hypoxia; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000276:immunology; D007668:Kidney / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D011247:Pregnancy / Q000097:blood* / Q000276:immunology; D044967:Serum; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D016753:Interleukin-10; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1