Endothelin-1 triggers placental oxidative stress pathways: putative role in preeclampsia.
BACKGROUND
Preeclampsia (PE) is a disorder that occurs only during pregnancy. The placenta has a controlling role in this condition. Recent literature suggests that the oxidative stress is a component of PE and plays a main role in the link between decreased placental perfusion and the impaired function of maternal endothelium.


OBJECTIVE
Because the human placenta expresses endothelin-1 (ET-1) and its circulating levels are high in pregnancies complicated with PE, the present study investigated the role of ET-1 on placental oxidative stress pathways.


METHODS
Human placental explants, JEG-3, and primary cytotrophoblast cells were cultured with increasing ET-1 concentrations for 6 and 24 h.


METHODS
The study was conducted at tertiary clinical care centers in Siena and Padova, Italy.


METHODS
Human placental explants, JEG-3, and primary cytotrophoblast cells were used to test ET-1 effect.


METHODS
The main outcome measure was ET-1 mRNA and its receptor mRNAs, type A and B, detection by RT-PCR. The common markers of oxidative stress [malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), ascorbic acid (AA)] as well as cell proliferation and vitality were measured after stimulation periods.


RESULTS
ET-1 inhibits cell proliferation and vitality and triggers oxidative stress in the human placenta by altering the balance between oxidant (increased MDA levels) and antioxidant (decreased GSH, GSSG, and AA) forces in favor of oxidation.


CONCLUSIONS
Because MDA damages endothelial cells, whereas GSH, GSSG, and AA protect them, we postulate that ET-1 may be one of the key links between primary placental disorders and the systemic endothelial dysfunction of PE.
Fiore
Giovina
G
Department of Obstetrics and Gynecology, Giorgio Segre, University of Siena, Siena, Italy.
Florio
Pasquale
P
Micheli
Lucia
L
Nencini
Cristina
C
Rossi
Marco
M
Cerretani
Daniela
D
Ambrosini
Guido
G
Giorgi
Giorgio
G
Petraglia
Felice
F
D045744:Cell Line, Tumor; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology*; D011247:Pregnancy
D019332:Endothelin-1; D005978:Glutathione