title: Effect of the anti-oxidant tempol on fetal growth in a mouse model of fetal growth restriction.
abstract: Fetal growth restriction (FGR) greatly increases the risk of perinatal morbidity and mortality and is associated with increased uterine artery resistance and levels of oxidative stress. There are currently no available treatments for this condition. The hypothesis that the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol) would improve uterine artery function and rescue fetal growth was tested in a mouse model of FGR, using the endothelial nitric oxide synthase knockout mouse (Nos3(-/-)). Pregnant Nos3(-/-) and control C57BL/6J mice were treated with the superoxide dismutase-mimetic Tempol (1 mmol/L) or vehicle from Gestational Day 12.5 to 18.5. Tempol treatment significantly increased pup weight (P < 0.05) and crown-rump length (P < 0.01) in C57BL/6J and Nos3(-/-) mice. Uterine artery resistance was increased in Nos3(-/-) mice (P < 0.05); Tempol significantly increased end diastolic velocity in Nos3(-/-) mice (P < 0.05). Superoxide production in uterine arteries did not differ between C57BL/6J and Nos3(-/-) mice but was significantly increased in placentas from Nos3(-/-) mice (P < 0.05). This was not reduced by Tempol treatment. Placental System A activity was reduced in Nos3(-/-) mice (P < 0.01); this was not improved by treatment with Tempol. Treatment of Nos3(-/-) mice with Tempol, however, was associated with reduced vascular density in the placental bed (P < 0.05). This study demonstrated that treatment with the antioxidant Tempol is able to improve fetal growth in a mouse model of FGR. This was associated with an increase in uterine artery blood flow velocity but not an improvement in uterine artery function or placental System A activity.
authors.affiliation: Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada. jlstanle@ualberta.ca
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Stanley
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Andersson
authors.forename: Cassandra J
authors.initials: CJ
authors.lastname: Hirt
authors.forename: Linn
authors.initials: L
authors.lastname: Moore
authors.forename: Mark R
authors.initials: MR
authors.lastname: Dilworth
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Chade
authors.forename: Colin P
authors.initials: CP
authors.lastname: Sibley
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
authors.forename: Philip N
authors.initials: PN
authors.lastname: Baker
mesh_terms: D026924:Amino Acid Transport System A / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D040761:Biomimetic Materials / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000502:physiology; D005317:Fetal Growth Retardation / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010920:Placenta / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D055988:Uterine Artery / Q000187:drug effects / Q000503:physiopathology
chemical_list: D026924:Amino Acid Transport System A; D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D013482:Superoxide Dismutase; C001803:tempol