title: Protective effect of maternal uteroplacental insufficiency on oxygen-induced retinopathy in offspring: removing bias of premature birth.
abstract: To address the hypothesis that maternal uteroplacental insufficiency (UPI) increases severity of retinopathy of prematurity, we developed a composite rat model of UPI and oxygen-fluctuations and removed premature birth as a confounding factor. Timed-pregnant Sprague-Dawley dams underwent bilateral uterine artery ligation or anesthesia (control) at e19.5. Full-term pups developed in room air (RA) or an oxygen-induced retinopathy (OIR) model. Isolectin-stained retinal flat-mounts were analyzed for percent of areas of avascular/total retina (AVA) and of intravitreal neovascular/total retina (IVNV). Pup weights and serum and mRNA of liver and kidney VEGF, IGF-1, and erythropoietin (EPO) were determined. Multivariable mixed effects linear regressions and Pearson correlations were performed using STATA14. Postnatal growth restriction occurred in pups in UPI/RA, but not in UPI/OIR. Weight gain was similar between UPI/OIR and control/OIR pups. AVA was reduced and a trend toward reduced IVNV was seen in UPI/OIR compared to control/OIR. No difference in birth weights of UPI/OIR vs. control/OIR pups occurred. Serum and renal IGF-1 and EPO were significantly increased in UPI/OIR compared to control/OIR pups. In the absence of prematurity, UPI increased angiogenic factors in association with reduced OIR severity, suggesting that ischemia from UPI could yield protective angiogenic effects by offspring.
authors.affiliation: John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: Silke
authors.initials: S
authors.lastname: Becker
authors.affiliation: John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Baifeng
authors.initials: B
authors.lastname: Yu
authors.affiliation: John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Brown
authors.affiliation: John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Han
authors.affiliation: Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lane
authors.affiliation: John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Hartnett
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D004195:Disease Models, Animal; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D010100:Oxygen; D010920:Placenta / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D047928:Premature Birth / Q000473:pathology*; D020011:Protective Agents / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000097:blood / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000097:blood / Q000473:pathology*; D014599:Uterus / Q000378:metabolism / Q000473:pathology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D020011:Protective Agents; D010100:Oxygen