title: Sex-related differences in long-term pulmonary outcomes of neonatal hyperoxia in mice.
abstract: OBJECTIVE
  Premature infants are often exposed to hyperoxia to maintain adequate oxygenation, which may lead to the development of bronchopulmonary dysplasia (BPD). Sex-specific differences exist in the development and severity of BPD. Only a few studies have examined the mechanisms underlying these sex-related differences. The aim of the present study is to examine the sex-related long-term effects of neonatal hyperoxia on the lungs of adult mice.
  
  
  METHODS
  Newborn mice were exposed to 95% oxygen (hyperoxia) for 96 hours and were allowed to recover in room air to adulthood (8 weeks of age). Lung tissues were excised at 4 days, 14 days, or 8 weeks of age. Short-term effects of neonatal hyperoxia on the mouse lung and sex-related differences in pulmonary function, airway hyper-responsiveness, and lung structure in adult mice were assessed.
  
  
  RESULTS
  Neonatal hyperoxia was found to have no differential effect on body weight, muscarinic acetylcholine receptor gene expression, or bronchiolar epithelial thickness in adult mice. Respiratory resistance was increased and sensitivity to methacholine was decreased in male adult mice following exposure to neonatal hyperoxia, whereas delayed alveolarization was observed in female adult mice following exposure to neonatal hyperoxia.
  
  
  CONCLUSIONS
  The findings of the present study demonstrate that neonatal hyperoxia differentially affects pulmonary outcome in female and male adult mice.
authors.affiliation: a Department of Pediatrics, Saitama Medical Center , Saitama Medical University , Kawagoe , Saitama , Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Namba
authors.affiliation: a Department of Pediatrics, Saitama Medical Center , Saitama Medical University , Kawagoe , Saitama , Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ogawa
authors.affiliation: a Department of Pediatrics, Saitama Medical Center , Saitama Medical University , Kawagoe , Saitama , Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ito
authors.affiliation: a Department of Pediatrics, Saitama Medical Center , Saitama Medical University , Kawagoe , Saitama , Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: b Department of Pediatrics , The Warren Alpert Medical School of Brown University , Providence , Rhode Island , USA.
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Dennery
authors.affiliation: a Department of Pediatrics, Saitama Medical Center , Saitama Medical University , Kawagoe , Saitama , Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tamura
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology*; D055745:Bronchioles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018496:Hyperoxia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011976:Receptors, Muscarinic / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012727:Sex Characteristics
chemical_list: D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010100:Oxygen
keywords: alveolarization; hyperoxia; neonate; pulmonary function; sex-difference