OBJECTIVE: To determine if the Thromboxane A2 analog model of Intrauterine Growth Restriction or postnatal hyperoxia exposure causes loss of oligodendroglia. DESIGN/METHODS: Pregnant C57Bl6 mice were implanted with micro-osmotic pumps containing Thromboxane A2 analog (U-46619) or 0.5% EtOH at E12.5. After spontaneous birth, pups were cross-fostered until sacrificed at P14 or P28. Pups weighing < 10th percentile at birth were considered to have intrauterine growth restriction (IUGR). Separate groups of vehicle and IUGR pups were placed into 75% FiO2 or room air from birth to P14. The brains were removed, post-fixed, and cryo-sectioned. Immunofluorescence was performed probing for the transcription factors Olig1 (marks the entire oligodendroglial (OL) lineage), Olig2 (marks oligodendrocyte progenitor cells (OPCs)), 2,3-Cyclic nucleotide 3, phosphodiesterase (CNPase) and Myelin basic protein (MBP) (mark mature OLs). 40x images of corpus callosum were taken and cells or marker expression were quantified. Two-way ANOVA analysis was used to analyze the data. RESULTS: P14 Thromboxane vs vehicle (TXA2 n=22, Veh n=9): There is a significant decrease in Olig1+ (TXA2: 424.3±29.9, veh: 674.1±50.2 (cells/mm2±s.e.m.) p= < 0.0001) and Olig2+ (TXA2: 661.6±81.4, veh: 1109.5±46.2 p=0.007) in the TXA2-treated group. There is a trend towards decrease in MBP that did not meet significance. P28 Thromboxane vs vehicle (TXA2 n=6, Veh n=6): There is a trend toward decrease in Olig 1+, Olig 2+, CNPase, and MBP expression that did not meet significance. P14 Hyperoxia vs normoxia (vehicle hyperoxia (vehO2) n=5, vehicle normoxia (vehRA) n=9, TXA2 hyperoxia (TXA2O2) n=13, TXA2 normoxia (TXA2RA) n=22): There is a significant decrease in Olig1+ (vehO2: 483.3±84.6, vehRA: 674.1±50.2, p=0.05) and Olig2+ (vehO2: 637.9±38.2, vehRA: 1109.5±46.2, p=0.02) with hyperoxia in vehicles. There is a decrease in MBP that did not meet significance. No significant difference found with hyperoxia exposure in IUGR model. P28 Hyperoxia vs normoxia (vehO2, vehRA, TXA2O2, TXA2RA n=6): There is a significant decrease in Olig2+ (vehO2: 817.1±126.3, vehRA: 1305.8±145.5, p=0.04), CNPase (vehO2: 4610.8±602.5, vehRA: 5822.4±220.2, (mean intensity±s.e.m.) p=0.05) and MBP expression (vehO2: 5830.1±304.1, vehRA: 6701.9±232.8, p=0.04) with hyperoxia exposure in vehicles. In the IUGR model there is a significant decrease only in Olig2+ (TXA2O2: 648.9±107.2, TXA2RA: 982.3±54.8, p=0.05). CONCLUSIONS: The TXA2 analog model of IUGR results in deleterious effect on white matter with significant reduction in OPCs and total OL lineage. This effect on white matter does not persist to P28. Hyperoxia exposure alone also has a negative effect on white matter as evidenced by a significant decrease in OPCs and impaired myelination. These changes persist in later mouse development at P28. These findings have important clinical application suggesting that IUGR infants may benefit close neurodevelopmental follow-up and that postnatal oxygen exposure should be limited to prevent white matter injury.