Abstract
Objectives
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.
Study design
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 12 h 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.
Keywords
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Article info
Publication history
Published online: September 21, 2007
Accepted:
August 22,
2007
Received in revised form:
August 5,
2007
Received:
August 2,
2006
Footnotes
☆The paper contains data that has been presented at, and awarded a prize by, the German Society for Gynaecology and Obstetrics in 2004.
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
