Effect of prenatal sulforaphane (SUL) on hyperoxia-induced lung injury in Nrf2+/+ and Nrf2-/- neonates

Results: Prenatal SUL altered baseline lung genes involved in organ/cell development and grow (e.g., Ibsp, Ctsk, Igfbp5) and ARE responses (e.g., Aldh3a1, Maff, Mafg) in Nrf2+/+ neonates and in cell morphogenesis and cell death and organismal injury/abnormality inhibition (e.g., Neat1, Nox4, Vegfa, Igfbp2, Trp53) in Nrf2-/- neonates. In hyperoxia-exposed lung, prenatal SULincreased organogenesis/development genes (e.g., Prss35, Cep128) and decreased inflammatory genes (H2-D1, Cd40, Lcn2, Cdh22) in Nrf2+/+ pups. In Nrf2-/- mice exposed to hyperoxia, prenatal SFN decreased hyperoxia-upregulated many immune and inflammatory response genes (e.g., Ccl9, Btla, Ncf4, Ltb, Selplg, Csf2rb) and upregulated many DNA repair/damage checkpoint genes (e.g., Uimc1, Neil3, Nbn, Smc4, Smc6). Conclusion: Overall, prenatal maternal SUL altered genes differentially in Nrf2+/+ and Nrf2-/- lungs. However, SUL-mediated transcriptome changes affected similar biological functions benificial to host defense and organ development in both strain. Compensatory differential lung transcriptome changes in Nrf2-/- neonates may resulted in the manifest protection of their severe hyperoxic lung injury. PARALLEL study design with 21 samples comparing 8 groups of prenatal treatment (PBS, SUL), gene (Nrf2-WT, Nrf2-KO), and postnatal exposure: (air, O2) (4 groups of Nrf2-WT; PBS/air, SUL/air, PBS/O2, SUL/O2), (4 groups of Nrf2-KO; PBS/air, SUL/air, PBS/O2, SUL/O2) Biological replicates: 2 or 3 per group