Altered canonical Wingless-It signaling in the ovine fetal lung after exposure to intra-amniotic lipopolysaccharide and antenatal betamethasone

Elke Kuypers, Monique G. M. Willems, Jennifer J. P. Collins, Tim G. A. M. Wolfs, Ilias Nitsos, J. Jane Pillow, Graeme R. Polglase, Matthew W. Kemp, John P. Newnham, Tammo Delhaas, Alan H. Jobe, Suhas G. Kallapur, Boris W. Kramer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Antenatal inflammation and maternal corticosteroids induce fetal lung maturation but interfere with late lung development. Canonical Wingless-It (Wnt) signaling directs lung development and repair. We showed that intraamniotic (IA) lipopolysaccharide (LPS) exposure disrupted developmental signaling pathways in the preterm lamb lungs. Therefore, we hypothesized that pulmonary Wnt signaling was altered by exposure to IA LPS and/or antenatal corticosteroids. METHODS: Ovine fetuses were exposed to IA LPS, maternal intramuscular betamethasone, a control saline injection, or a combination thereof at 107 and/or 114 d gestational age (term = 150 d gestational age) before delivery at 121 d gestational age. RESULTS: IA LPS exposure decreased the lung expression of lymphoid enhancer-binding factor 1 (LEF1), a major Wnt pathway effector. WNT1, WNT4, and downstream messenger beta-catenin decreased after LPS exposure. WNT7b mRNA increased fourfold 14 d post LPS exposure. Betamethasone treatment 7 d before LPS exposure prevented the reduction in LEF1 expression, whereas betamethasone administration after LPS normalized the LPS-induced increase in Wnt7b mRNA. CONCLUSION: IA LPS exposure decreased canonical Wnt signaling in the developing lung. Antenatal corticosteroids before or after IA inflammation had different effects on pulmonary Wnt signaling. This study provides new insights into possible mechanisms by which prenatal inflammation affects lung development and how corticosteroid can be beneficial in this setting.
Original languageEnglish
Pages (from-to)281-287
JournalPediatric Research
Issue number2
Publication statusPublished - Feb 2014

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