Delay in rat lung alveolarization after the combined exposure of maternal hyperglycemia and postnatal hyperoxia

Maternal diabetes interferes with fetal lung development and postnatal treatments may further disturb pulmonary growth. Therefore, we investigated the effect of postnatal oxygen exposure on alveolar development in neonatal rat lungs pre-exposed to intrauterine hyperglycemia.Diabetes was induced in Sprague-Dawley rats with streptozotocin injection before pregnancy. Hyperglycemia-exposed and control litters were randomized to breath room air or 85% oxygen for 7 days after birth. Lungs were analyzed on postnatal d7 for weight, morphology, apoptosis, proliferation, and biomarkers of oxidative stress.Maternal hyperglycemia accelerated lung development as demonstrated by thinner alveolar walls and slightly increased secondary septation when compared to room air bred rats. Hyperoxia alone caused thin-walled and enlarged alveoli with few secondary septa. Interestingly, the dual exposure inhibited the thinning of alveolar walls and the disappearance of mesenchymal cells from the alveolar walls together with the delay in the formation of alveoli and secondary crests. While the lungs' oxidative stress was similar in all groups, pulmonary apoptosis and proliferation were altered.Our results thus indicate that the hyperglycemic priming of the fetal lung modifies the deleterious effect of hyperoxia on alveolarization in neonatal rats.