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EFFECTS OF PRENATAL PERFLUOROOCTANESULFONATE (PFOS) EXPOSURE ON LUNG MATURATION IN THE PERINATAL RAT
Citation:
GRASTY, R., N. L. ROBERTS, G. R. KLINEFELTER, J. A. BJORK, K. B. WALLACE, C. S. LAU, AND J. M. ROGERS. EFFECTS OF PRENATAL PERFLUOROOCTANESULFONATE (PFOS) EXPOSURE ON LUNG MATURATION IN THE PERINATAL RAT. Presented at Teratology Society Meeting, St. Pete Beach, FL, June 26 - 30, 2005.
Description:
PFOS is an environmentally stable compound that has been detected at 3 ppb -10 ppm in serum samples from the general public and occupationally exposed individuals. We have shown that exposing pregnant rats to PFOS (25, or 50 mg/kg/d on GD 19-20) induces neonatal death in the rat; the underlying pathophysiological mechanism remains unknown. Results from histological and morphometric analyses suggested that lungs from PFOS-exposed pups had thicker alveolar walls and were immature compared to those of controls. We hypothesized that in utero exposure interrupted maturation of the terminal airway epithelium, leading to respiratory distress in the neonate. To further evaluate the effect of PFOS exposure on the developing lung, pregnant Sprague-Dawley rats were treated orally with 0, 25, or 50 mg/kg/d PFOS/K+ on GD 19-20. Pulmonary surfactant production was evaluated in GD 21 amniotic fluid and whole lungs from newborn rats by electrospray ionization tandem mass spectrometry. No significant changes in absolute or relative phospholipid concentrations were detected and molecular speciation appeared unaffected by PFOS exposure. Additionally, microarray analysis was performed on newborn lung. No significant changes in markers of alveolar cell differentiation or maturation were detected. Ultrastructural evaluation of the alveolar cells indicated an increase in stored lamellar bodies and the presence of unidentified striated structures in the 50 mg/kg group. These findings were not seen in prenatal samples. To identify potential components of the structures, F-actin and ?-tubulin were analyzed in newborn lung tissue using immunocytochemistry. No differences in expression of either protein were observed between lungs of control and PFOS-exposed neonates. Finally, surfactant protein-B (SP-B) expression in bronchoalveolar lavage fluid of newborn rats was compared. Western blot analysis confirmed that SP-B expression was similar between samples. These results indicate that despite a mild histologic immaturity, lungs of PFOS-exposed pups were capable of synthesizing and secreting normal pulmonary surfactant. Further work will be necessary to elucidate mechanisms of PFOS respiratory toxicity. This abstract does not reflect EPA policy; funded by EPA/UNC CT 902908.