Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation
Micka C. Bertucci A , Jan M. Loose B , Euan M. Wallace B , Graham Jenkin B and Suzanne L. Miller B C
+ Author Affiliations
- Author Affiliations
A Department of Physiology, Monash University, Clayton, Vic. 3168, Australia.
B Department of Obstetrics and Gynaecology and The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Vic. 3168, Australia.
C Corresponding author. Email: suzie.miller@monash.edu
Reproduction, Fertility and Development 23(2) 346-352 https://doi.org/10.1071/RD10110
Published: 4 January 2011
Abstract
Perinatal morbidity and mortality are significantly higher in pregnancies complicated by chronic hypoxia and intrauterine growth restriction (IUGR). Clinically, placental insufficiency and IUGR are strongly associated with a fetoplacental inflammatory response. To explore this further, hypoxia was induced in one fetus in twin-bearing pregnant sheep (n = 9) by performing single umbilical artery ligation (SUAL) at 110 days gestation. Five ewes were administered the anti-inflammatory drug sulfasalazine (SSZ) daily, beginning 24 h before surgery. Fetal blood gases and inflammatory markers were examined. In both SSZ- and placebo-treated ewes, SUAL fetuses were hypoxic and growth-restricted at 1 week (P < 0.05). A fetoplacental inflammatory response was observed in SUAL pregnancies, with elevated pro-inflammatory cytokines, activin A and prostaglandin E2. SSZ did not mitigate this inflammatory response. It is concluded that SUAL induces fetal hypoxia and a fetoplacental inflammatory response and that SSZ does not improve oxygenation or reduce inflammation. Further studies to explore whether alternative anti-inflammatory treatments may improve IUGR outcomes are warranted.
Additional keywords: intrauterine growth restriction, placental insufficiency, sheep.
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