title: Placental structural abnormalities have detrimental hemodynamic consequences in a rat model of maternal hyperglycemia.
abstract: Human type 1 diabetic pregnancy is associated with placental structural and hemodynamic abnormalities. We hypothesized that in rat fetuses of hyperglycemic dams, placental and fetal blood flow velocity waveforms demonstrate compromised hemodynamics when compared to control fetuses, and these hemodynamic parameters correlate with placental structural abnormalities at near term gestation.
  
  
  
  Streptozotocin-induced maternal hyperglycemia group comprised 10 dams with 107 fetuses and the control group 20 dams with 219 fetuses. Doppler-ultrasonographic examinations were performed at gestational days 13-14, 16-17, and 19-21. After the last examination, placentas were collected for morphologic, gene expression, and cytokine analysis.
  
  
  
  Umbilical artery (UA), descending aorta (DAO), and ductus venosus (DV) pulsatility indices (PI) were significantly higher at each study point in maternal hyperglycemia compared to controls. Placental size, glycogen storages, venous thrombosis formation, and fluid accumulation were increased in maternal hyperglycemia. Epidermal growth factor receptor (Edgfrb), platelet derived growth factor receptor beta polypeptide (Pdgfrb), and tumor necrosis factor receptor superfamily, member 12α (Tnfrsf12α) expressions were decreased. Interleukin (IL) -2 and -4 concentrations were decreased, and IL-1beta levels were increased in maternal hyperglycemia. UA PIs correlated positively with DV PIV, DAO PI, fluid accumulation, and glycogen storages. UA PIs correlated negatively with IL-4, Edgfrb, and Pdgfrb.
  
  
  
  In maternal hyperglycemia, placental and fetal hemodynamics were compromised during the last trimester of pregnancy compared to normoglycemic pregnancies. Placental structural, metabolic, and growth related gene expression, and inflammatory marker abnormalities were associated with hemodynamic compromise.
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland; Institute of Biomedicine, Department of Physiology, University of Oulu, Finland; The Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University of Turku, Finland. Electronic address: lara.lehtoranta@utu.fi.
authors.forename: Lara
authors.initials: L
authors.lastname: Lehtoranta
authors.affiliation: Institute of Biomedicine, Department of Physiology, University of Oulu, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Vuolteenaho
authors.affiliation: Department of Pathology, Turku University Hospital, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Laine
authors.affiliation: Department of Cell Biology and Anatomy, University of Turku, and Turku Center for Disease Modeling (TCDM), Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Polari
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Ekholm
authors.affiliation: Institute of Biomedicine, Department of Physiology, University of Oulu, Finland; Department of Obstetrics and Gynecology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland; Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Räsänen
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006943:Hyperglycemia / Q000473:pathology / Q000503:physiopathology*; D010920:Placenta / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014469:Umbilical Arteries / Q000503:physiopathology*
keywords: Animal model; Circulation; Impedance; Maternal hyperglycemia; Placenta