title: Hyperglycemia, hypoxia and their combination exert oxidative stress and changes in antioxidant gene expression: studies on cultured rat embryos.
abstract: BACKGROUND
  Hyperglycemia and hypoxia are well-known teratogens that may affect many animal species, including man. We hypothesize that a combination of hypoxia and hyperglycemia will increase embryonic damage produced by either factor individually. We investigated the interrelationship between hyperglycemia and hypoxia and their effects on genes involved in the balance of embryonic redox status.
  
  
  METHODS
  Rat embryos (10.5-day-old) were cultured for 28 hr in culture medium with about 6 mg/ml of glucose and 20% oxygen (hyperglycemia), with 10% oxygen (hypoxia) and 2.4 g/ml glucose (normal) or a combination of both 6 mg/ml glucose and 10% oxygen. Antioxidant capacity was determined by activity and gene expression of antioxidant enzymes: Cu/Zn SOD, Mn-SOD, CAT, and GSH-px using real time PCR.
  
  
  RESULTS
  Hyperglycemia, hypoxia, or their combination, decreased embryonic growth and induced a high rate (62-78%) of anomalies mainly of the nervous system, heart, and limbs. CAT mRNA and GSH-px mRNA were decreased in the malformed embryos exposed to hyperglycemia, to hypoxia or their combination. CAT mRNA was also decreased in the nonmalformed embryos subjected to hyperglycemia and hypoxia. Cu/Zn SOD mRNA was increased in all experimental embryos whether malformed or not, whereas Mn-SOD was drastically decreased. Total SOD and CAT like activity were changed very little in the experimental embryos compared to controls.
  
  
  CONCLUSIONS
  Both hyperglycemia, hypoxia, and their combination reduce embryonic growth and development, induce embryonic anomalies, and modify the expression of the principle antioxidant genes. However, hypoxia does not seem to enhance the damaging effects of hyperglycemia except its effects of embryonic growth.
authors.affiliation: Laboratory of Teratology, Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem, Israel. ornoy@cc.huji.ac.il
authors.forename: Asher
authors.initials: A
authors.lastname: Ornoy
authors.forename: Alicia
authors.initials: A
authors.lastname: Livshitz
authors.forename: Zivanit
authors.initials: Z
authors.lastname: Ergaz
authors.forename: Chais J
authors.initials: CJ
authors.lastname: Stodgell
authors.forename: Richard K
authors.initials: RK
authors.lastname: Miller
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000235:genetics*; D000860:Hypoxia / Q000150:complications / Q000235:genetics*; D008297:Male; D009994:Osmolar Concentration; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D019170:Somites / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques / Q000379:methods*; D015017:Yolk Sac / Q000187:drug effects
chemical_list: D000975:Antioxidants; D003470:Culture Media; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase