title: Proliferative responses in the placenta after endotoxin exposure in preterm fetal sheep.
abstract: OBJECTIVE
  Antenatal infections are associated with an increased risk of perinatal morbidity and mortality. Systemic application of endotoxins to the fetus results in an increase in placental vascular resistance and chronic reduction in umbilical blood flow. We studied morphological alterations of the placenta in response to fetal inflammation in the preterm sheep.
  
  
  METHODS
  Therefore, 14 fetal sheep were chronically instrumented at a mean gestational age of 107+/-1 days (term is 147 days). Four days after surgery fetuses received 100 ng lipopolysaccharide (LPS; n=8) or saline (control; n=6) intravenously. Fetal heart rate and arterial blood pressure were monitored continuously while blood gases and acid-base balance were measured at time points 0, +1, +3, +6, +12, +24, +48 and +72 h. Three days after LPS application placental cotyledons were analyzed by immunohistochemistry and morphometry. Different primary antibodies like AE 1 and AE 3 against cytokeratins were used. Secondary antibodies were visualized with 3-amino-9-ethylcarbazole (AEC) or using the Vectastain kit (Vector Laboratories, Burlingame, CA). Double staining was carried out first by utilizing Vectastain kit (black), followed by AEC staining (red). Counterstaining was performed with haematoxylin.
  
  
  RESULTS
  Fetal tachycardia and hypertension were induced transiently during the first 12h after LPS application. Fetuses suffered from mild hypoxaemia while acidemia was absent. Morphometry revealed a non-significant shift in the relation of maternal and fetal placental compartments towards the maternal parts in response to LPS treatment. Endotoxin induced an increased proliferation in both compartments of the placenta with a 3.2-fold increase on the maternal and a 1.8-fold increase on the fetal side.
  
  
  CONCLUSIONS
  Systemic endotoxin exposure of the preterm fetal sheep leads to a change in the gross organization of the placenta and changes in the proliferation patterns in both placental compartments. These rearrangements inside the placenta may disturb its organ function and subsequently lead to fetal morbidity associated with the fetal inflammatory response syndrome and chronic placental dysfunction, respectively.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital RWTH Aachen, Germany. yves.garnier@uk-koeln.de
authors.forename: Yves
authors.initials: Y
authors.lastname: Garnier
authors.forename: Mamed
authors.initials: M
authors.lastname: Kadyrov
authors.forename: Markus
authors.initials: M
authors.lastname: Gantert
authors.forename: Anke
authors.initials: A
authors.lastname: Einig
authors.forename: Werner
authors.initials: W
authors.lastname: Rath
authors.forename: Berthold
authors.initials: B
authors.lastname: Huppertz
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019332:Endothelin-1 / Q000502:physiology; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006340:Heart Rate, Fetal / Q000187:drug effects; D007249:Inflammation / Q000209:etiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects / Q000473:pathology*; D011247:Pregnancy; D012756:Sheep
chemical_list: D019332:Endothelin-1; D008070:Lipopolysaccharides