Preeclampsia-like symptoms induced in mice by fetoplacental expression of STOX1 are reversed by aspirin treatment.
Preeclampsia (PE) is a common human-specific pregnancy disorder defined by hypertension and proteinuria during gestation and responsible for maternal and fetal morbimortality. STOX1, encoding a transcription factor, was the first gene associated with PE as identified by positional cloning approaches. Its overexpression in choriocarcinoma cells mimics the transcriptional consequences of PE in the human placenta. Here, we created transgenic mouse strains overexpressing human STOX1. Wild-type female mice crossed with transgenic male mice reproduce accurately the symptoms of severe PE: gestational hypertension, proteinuria, and elevated plasma levels of soluble fms-like tyrosine kinase 1 and soluble endoglin. Placental and kidney histology were altered. Symptoms were prevented or alleviated by aspirin treatment. STOX1-overexpressing mice constitute a unique model for studying PE, allow testing therapeutic approaches, and assessing the long-term effects of the preeclamptic syndrome.
INSERM U1016-CNRS UMR8104, Paris, France.
Ludivine
L
Doridot
Bruno
B
Passet
Céline
C
Méhats
Virginie
V
Rigourd
Sandrine
S
Barbaux
Aurélien
A
Ducat
Françoise
F
Mondon
Marthe
M
Vilotte
Johann
J
Castille
Michelle
M
Breuiller-Fouché
Nathalie
N
Daniel
Fabienne
F
le Provost
Anne-Laure
AL
Bauchet
Véronique
V
Baudrie
Alexandre
A
Hertig
Christophe
C
Buffat
Umberto
U
Simeoni
Guy
G
Germain
Jean-Luc
JL
Vilotte
Daniel
D
Vaiman
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000009:adverse effects / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D000071063:Endoglin; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D011247:Pregnancy; D012720:Severity of Illness Index; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D002352:Carrier Proteins; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C500784:STOX1 protein, human; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D001241:Aspirin