Elevation of both cyclooxygenase-2 and prostaglandin E2 receptor EP3 expressions in rat placenta after uterine artery ischemia-reperfusion.
Intrauterine growth restriction (IUGR) has a multifactorial pathogenesis and is an important cause of perinatal mortality. The relationship between fetal weight and placental blood flow in an animal model of IUGR has been investigated, showing that fetal growth is regulated by placental blood flow. The aim of the present study was to determine whether ischemia-reperfusion (I/R) injury stimulates the prostaglandin E2 (PGE2) system or the vascular endothelial growth factor (VEGF) system in the placenta of a rat IUGR model. COX-2 is reported to be involved in ischemic damage in many organs. There are 4 types of PGE2 receptor (EP1, EP2, EP3 and EP4). It is well known that EP1 and EP3 is associated with vasoconstriction. In the present study, vessels were occluded in the right uterine horn on day 17 of pregnancy in rats, and the clamps were removed after 30 min of ischemia. At 24h, 48 h, and 5 days after I/R injury, the live fetuses and placentas were obtained by cesarean section. This study revealed that I/R injury caused IUGR 5 days after the treatment. COX-2 expression and EP3 receptor expression were significantly elevated at 24h after I/R injury, but VEGF mRNA expression was not altered in the placenta from the ischemic horn compared with the non-ischemic horn. These results suggested that induction of the COX-2-EP3 system in the placenta may be one of the causes of IUGR induced by uterine ischemia, because the EP3 receptor and PGE2 are well known to mediate vasoconstriction in many organs.
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South 1 West 16 Sapporo 060-8543, Japan.
K
K
Yamazaki
T
T
Endo
Y
Y
Kitajima
K
K
Manase
K
K
Nagasawa
H
H
Honnma
T
T
Hayashi
R
R
Kudo
T
T
Saito
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D020567:Fetal Weight; D007150:Immunohistochemistry; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015427:Reperfusion Injury / Q000378:metabolism; D013997:Time Factors; D014599:Uterus / Q000098:blood supply; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C545649:Ptger3 protein, rat; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2