Proliferative responses in the placenta after endotoxin exposure in preterm fetal sheep

Garnier, Yves; Kadyrov, Mamed; Gantert, Markus; Einig, Anke; Rath, Werner; Huppertz, Berthold

doi:10.1016/j.ejogrb.2007.08.016

« Previous Next »European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 138, Issue 2 , Pages 152-157, June 2008

Proliferative responses in the placenta after endotoxin exposure in preterm fetal sheep☆

Yves Garnier
- Department of Obstetrics and Gynecology, University Hospital RWTH Aachen, Germany
- Department of Obstetrics and Gynecology, University Hospital Cologne, Germany
- Corresponding author at: University Hospital of Cologne, Department of Obstetrics and Gynecology, Kerpenerstrasse 34, D-50924 Cologne, Germany. Tel.: +49 221 478 4910; fax: +49 221 478 4929.
Mamed Kadyrov
- Institute of Anatomy II, University Hospital RWTH Aachen, Germany
Markus Gantert
- Department of Obstetrics and Gynecology, University Hospital RWTH Aachen, Germany
- Department of Obstetrics and Gynecology, University Hospital Cologne, Germany
Anke Einig
- Department of Obstetrics and Gynecology, University Hospital RWTH Aachen, Germany
- Institute of Anatomy II, University Hospital RWTH Aachen, Germany
Werner Rath
- Department of Obstetrics and Gynecology, University Hospital RWTH Aachen, Germany
Berthold Huppertz
- Institute of Anatomy II, University Hospital RWTH Aachen, Germany
- Institute of Cell Biology, Histology and Embryology, Medical University Graz, Austria

Received 2 August 2006; received in revised form 5 August 2007; accepted 22 August 2007. published online 21 September 2007.

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 100ng 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 +72h. 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.

Keywords: Fetal inflammatory response syndrome, Chorioamnionitis