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PREGNANCY LOSS ASSOCIATED WITH EXPOSURE TO PERFLUOROOCTANOIC ACID IN THE MOUSE
Citation:
LAU, C. S., J. R. THIBODEAUX, L. THAI, R. HANSON, M. R. BLANTON, E. S. HUNTER, B. D. ABBOTT, AND M J. STRYNAR. PREGNANCY LOSS ASSOCIATED WITH EXPOSURE TO PERFLUOROOCTANOIC ACID IN THE MOUSE. Presented at Teratology Society Meeting, St. Pete Beach, FL, June 25 - 30, 2005.
Description:
Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acids that have unique surfactant properties and are widely used in industrial and consumer products. These chemicals are stable and persistent in the environment; recent bio-monitoring studies have indicated wide-spread presence of PFOA in humans and wildlife. Results from our previous studies have suggested that PFOA is a developmental toxicant in the mouse, although frank terata were noted primarily in high-dose group. In the present study, daily administration of PFOA (20 or 40 mg/kg) by oral gavage to pregnant CD-1 mice from GD 1-17 led to 75% and 100% incidence respectively, of total resorption at term. Corresponding maternal serum PFOA levels of 0.18 mg/ml and 0.27 mg/ml were found at term in these two groups of mice. In a separate study, mouse embryos were examined on GD 7 and GD 8 after the initiation of daily PFOA (20 mg/kg) treatment on GD 1. PFOA did not alter the total number of implantations, but significantly reduced the percent of live implants on GD 7 (55%) and GD 8 (34%). To explore the underlying mechanisms of the PFOA-induced early pregnancy loss, mouse embryos at 3-6 somite stage were cultured for 24 h in a series of PFOA concentrations ranging from 0.1 to 1.25 mg/ml. Embryonic morphology was assessed and scored from 0 (normal) to 58 (severely abnormal). Accordingly, control embryos scored 0.4, and those exposed to 0.1 mg/ml and 0.2 mg/ml PFOA scored 0 and 1.7 respectively. Significant increases in score were detected in embryos exposed to 0.4 mg/ml PFOA (11.3), 0.6 mg/ml (11.3), 0.75 mg/ml (23.5) and 1 mg/ml (31.1). Abnormalities included prosencephalic and pharyngeal arch hypoplasia and altered heart outflow tract development. Exposure to 1.25 mg/ml PFOA produced 100% embryolethality. These data indicated that while PFOA was capable of disrupting embryonic development in culture, it did so at concentrations above those detected in the maternal serum where resorptions were observed at term. Hence, mouse embryos at the early neurulation stage were not particularly sensitive to PFOA-induced dysmorphology and lethality. Together, these studies suggest that the PFOA-induced pregnancy loss in the mouse is likely associated with maternal factors and/or a critical stage of the embryonic development during the peri-implantation period, and may explain the relatively low teratogenic potential of PFOA in the in vivo study. This abstract does not necessarily reflect EPA policy.