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Title: Inhibition of trophoblast-induced spiral artery remodeling reduces placental perfusion in rat pregnancy
Authors: Verlohren, Stefan ×
Geusens, Nele
Morton, Jude
Verhaegen, Iris
Hering, Lydia
Herse, Florian
Dudenhausen, Joachim W
Muller, Dominik N
Luft, Friedrich C
Cartwright, Judith E
Davidge, Sandra T
Pijnenborg, Robert
Dechend, Ralf #
Issue Date: Aug-2010
Publisher: Lippincott Williams & Wilkins
Series Title: Hypertension vol:56 issue:2 pages:304-U240
Abstract: Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity. We tested the hypothesis that matrix metalloproteinase inhibition reduces trophoblast invasion with subsequent changes in placental perfusion. Preeclamptic and pregnant control Sprague-Dawley rats were treated with doxycycline (30 mg/kg of body weight orally) from gestational day 12 until day 18. Placental perfusion was assessed using a micromarker contrast agent. The animals were euthanized on day 18 of pregnancy; biometric data were acquired, and trophoblast invasion was analyzed. Doxycycline resulted in intrauterine growth retardation and lighter placentas in both groups. Maternal body weight was not affected. As shown earlier, preeclamptic rats exhibited a deeper endovascular trophoblast invasion. However, doxycycline treatment reduced trophoblast invasion in the preeclamptic rats. The physiological spiral artery remodeling, as assessed by the deposition of fibrinoid and alpha-actin in the spiral artery contour, was significantly reduced by doxycycline. The vascularity index, as assessed by perfusion measurement of the placenta, was reduced after doxycycline treatment in preeclamptic rats. Thus, matrix metalloproteinase inhibition with doxycycline leads to reduced trophoblast invasion and associated reduced placental perfusion. These studies are the first to show that reducing trophoblast-induced vascular remodeling decreases subsequent placental perfusion. Our model allows the study of dysregulated trophoblast invasion and vascular remodeling in vivo to gain important insights into preeclampsia-related mechanisms.
URI: 
ISSN: 0194-911X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pathophysiology of Pregnancy Section (-)
Section Woman - Miscellaneous (-)
× corresponding author
# (joint) last author

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