Placental oxidative stress in a rat model of preeclampsia.
The onset of preeclampsia is associated with increased maternal insult that could affect placental function. By increasing sodium intake (0.9% or 1.8% NaCl in drinking water) during the last week of gestation in the rat, we developed an animal model that shows many characteristics of preeclampsia such as increased blood pressure, decreased circulatory volume and diminished activity of the renin-angiotensin-aldosterone system. The aim of the present study was to determine in this model whether maternal perturbations in pregnancy lead to placental oxidative stress. Sprague-Dawley pregnant rats receiving salted-water were compared to not-supplemented pregnant rats. Markers of oxidative stress, ensuing cell death, and changes in the production of vasoactive substances (prostanoids: thromboxane, TxB(2); and prostacyclin, PGF(1alpha)) and the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) were measured in the placenta. In tissue from pregnant rats on 1.8% NaCl supplement, 8-iso-PGF(2alpha) levels, TxB(2)/6-keto-PGF(1alpha) ratios, total TNF-alpha RNA expression, as well as the apoptotic index (Bax/Bcl-2 ratio) and endothelial nitric oxide synthase protein expression increase while total glutathione content decreases. These findings demonstrate that maternal insult during gestation induced an imbalance in the oxidative environment in the placenta favouring oxidation. This was accompanied by an increased synthesis of vasoconstrictive substances and TNF-alpha by the placenta as well as the increased rate of placental cell apoptosis.
Research Centre, Hôpital Sainte-Justine, 3175 Côte Sainte-Catherine, Montreal, QC, Canada H3T 1C5.
A
A
Beauséjour
K
K
Bibeau
J-C
JC
Lavoie
J
J
St-Louis
M
M
Brochu
D000818:Animals; D017209:Apoptosis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005978:Glutathione / Q000032:analysis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011453:Prostaglandins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D052250:Nitric Oxide Synthase Type III; D005978:Glutathione