title: Impaired nephrogenesis in neonatal rats with oxygen-induced retinopathy.
abstract: BACKGROUND
  Preterm neonates are born while nephrogenesis is ongoing, and are commonly exposed to factors in a hyperoxic environment that can impair renal development. Oxidative stress has also been implicated in the development of retinopathy of prematurity (ROP). The rat model of oxygen-induced retinopathy (OIR) is the most clinically relevant model of ROP because its biologic features closely resemble those of ROP in preterm infants. We investigated impaired renal development in a rat model of OIR.
  
  
  METHODS
  Newborn Sprague-Dawley rats were maintained in either a normoxic (room air, 21% O2; control group) or a controlled hyperoxic (80% O2; OIR group) environment from birth to postnatal day (P) 12. All pups were then raised in room air from P12 to P19.
  
  
  RESULTS
  The hyperoxic environment led to significantly higher urinary excretion of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage, and a reduction in nephrogenic zone width at P5 in OIR pups. Additionally, glomerular count was significantly reduced by 20% in the OIR group, and avascular and neovascular changes in the retina were observed only in the OIR group at P19. Messenger RNA levels of vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor-β, essential angiogenic cytokines for glomerulogenesis, in the renal cortex were significantly lower at P5 and significantly higher at P19 in the OIR group compared with controls.
  
  
  CONCLUSIONS
  Renal impairment was caused by exposure to a hyperoxic environment during nephrogenesis, and the pathology of the impaired nephrogenesis in this OIR model reflects the characteristics of ROP observed in preterm infants.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Mayu
authors.identifier: http://orcid.org/0000-0002-8814-6885
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nishizaki
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Amane
authors.initials: A
authors.lastname: Endo
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Tomonosuke
authors.initials: T
authors.lastname: Someya
authors.affiliation: Department of Ophthalmology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mizutani
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Murano
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sakuraya
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hara
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Umino
authors.affiliation: Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Daishi
authors.initials: D
authors.lastname: Hirano
authors.affiliation: Department of Nephrology, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Fujinaga
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Yoshiyuki
authors.identifier: http://orcid.org/0000-0002-5436-143X
authors.initials: Y
authors.lastname: Ohtomo
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018496:Hyperoxia / Q000150:complications*; D007668:Kidney / Q000254:growth & development*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000209:etiology*; D012178:Retinopathy of Prematurity / Q000209:etiology / Q000503:physiopathology*; D012307:Risk Factors
keywords: neonatal hyperoxia; nephrogenesis; preterm infant; retinopathy of prematurity; vascular endothelial growth factor-A