Oxidative Stress in Fetal Lambs Exposed to Intra-amniotic Endotoxin in a Chorioamnionitis Model

Chorioamnionitis is a risk factor for the development of bronchopulmonary dysplasia. Endotoxin-induced oxidative stress to the fetus in the uniquely hypoxic intrauterine environment has not been reported. Using a model of chorioamnionitis, we measured markers of pulmonary and systemic oxidant exposures in fetal lambs at 124 d gestation (term = 150 d) exposed to 10 mg intra-amniotic endotoxin 2 d (n = 6) or 7 d (n = 6) before delivery, or saline as controls (n = 9). The 7 d endotoxin-exposed animals had 3-fold higher protein carbonyls (0.66 ± 0.46 versus 0.23 ± 0.14 nmol/mg protein) and 10-fold greater myeloperoxidase activity (2.38 ± 1.87 versus 0.27 ± 0.18 nM) in the bronchoalveolar lavage fluid (BALF), suggestive of neutrophil-derived oxidant activity. However, in the lung tissue, protein carbonyls, superoxide dismutase, and peroxiredoxin 1 were not different between groups. The expression of peroxiredoxin 1 was prominent, primarily in the peri-bronchiolar epithelium. Notably, evidence of oxidant exposure was minimal at 2 d when BALF inflammatory cells, lung IL-1β, and IL-8 were highest. Intra-amniotic endotoxin induced systemic oxidative stress as plasma protein carbonyl was elevated at 7 d (0.14 ± 0.04 nmol/mg protein; p = 0.005). Surfactant protein A and B mRNAs were highest at 2 d, suggesting that oxidative stress did not contribute to the lung maturation response. A modest lung oxidative stress in chorioamnionitis could contribute to bronchopulmonary dysplasia.