title: Endothelin Receptor A Antagonism Prevents Damage to Glycogen-Rich Placental Cells Following Uterine Ischemia-Reperfusion in the Rat.
abstract: Fetal growth restriction (FGR) is a common cause of perinatal morbidity and mortality. Suboptimal uteroplacental perfusion is the most commonly identified cause of FGR, and ischemic lesions are often observed in placentas from pregnancies complicated by FGR. Ischemia followed by reperfusion is a strong stimulus to the production of the vasoconstrictor endothelin 1 (ET-1) which has been implicated in several models of FGR. We sought to investigate oxidative stress and placental morphology in a rat model of ischemia-reperfusion (I/R)-induced FGR and to evaluate the role of ET-1 in the observed pathology. Unilateral uterine I/R (30 min) was conducted, with and without simultaneous ET-1 receptor A (ETA) antagonism, on pregnant rats at gestation day 17. Placental tissues collected 24 hours later were evaluated immunohistochemically for oxidative damage. Tissue pathology was studied using quantitative morphometry. Glycogen-rich cellular areas in the placental junctional zone exhibited only 50% intact cells (P < .001) in both uterine horns following unilateral I/R, compared to controls. ETAantagonism prevented damage to the glycogen-rich cellular areas. Oxidative damage in response to I/R was prominent in the labyrinthine layer in both uterine horns and was not affected by ETAantagonism. We conclude that glycogen-rich cellular areas of the placental junctional zone are particularly vulnerable to damage from uterine I/R in the rat. Nucleic acid oxidative damage in the labyrinth is a prominent effect of uterine I/R. ETAantagonism protects placental cellular integrity during I/R challenge but does not prevent nucleic acid oxidative damage.
authors.affiliation: Department of Obstetrics & Gynecology, NorthShore University HealthSystem, Evanston, IL, USA Department of Obstetrics & Gynecology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA Lthaete@northshore.org.
authors.forename: Larry G
authors.initials: LG
authors.lastname: Thaete
authors.affiliation: Department of Obstetrics & Gynecology, NorthShore University HealthSystem, Evanston, IL, USA Department of Pediatrics, University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
authors.forename: Saira
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Obstetrics & Gynecology, NorthShore University HealthSystem, Evanston, IL, USA Department of Obstetrics & Gynecology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Neerhof
mesh_terms: D000818:Animals; D065130:Endothelin A Receptor Antagonists / Q000008:administration & dosage*; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology*; D006003:Glycogen / Q000378:metabolism; D007511:Ischemia / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D009696:Nucleic Acids / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010920:Placenta / Q000187:drug effects* / Q000473:pathology*; D011247:Pregnancy; D011759:Pyrrolidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D014599:Uterus / Q000187:drug effects / Q000293:injuries / Q000473:pathology*
chemical_list: C467892:ABT 546; D065130:Endothelin A Receptor Antagonists; D009696:Nucleic Acids; D011759:Pyrrolidines; D006003:Glycogen
keywords: endothelin receptor antagonists; ischemia; oxidative stress; placenta; rats