MP7 Toxicogenomics in Environmental Studies
Monday, 14 November 2005: 8:00 AM - 5:30 PM in Exhibit Hall

(RAM-1117-835185) Pendrin gene expression in the gonads of deer mice following exposure to ammonium perchlorate.

Ramachandran, B¹, Viņas, R¹, Gentles, A¹, Cox, S¹, Smith, E¹, ¹ The Institute of Environmental and Human Health, Texas Tech University, Lubbock, Texas, USA.

ABSTRACT- Pendrin is a membrane transport protein, which functions in the transport of chloride, bicarbonate, and iodide. Perchlorate, a component of fuel for rockets and missiles, is a known disruptor of thyroid hormone homeostasis and iodide transport. The objective of this study was to characterize pendrin gene expression and evaluate the effects of ammonium perchlorate (AP) on pendrin expression in the gonads of deer mice, a sentinel wildlife species. Deer mice were exposed to AP (0, 58.5 and 117 ppm) either during gestation-alone (GA) or gestation and lactation (GL). The results indicate that conception was 100% in the control group while it was 75% and 58.33% in the low and high treatment groups, respectively. Litter size was significantly lower (p<0.05) in the highest AP exposure group compared to the other groups. Interestingly, the highest exposure group had the highest pup survival percentage through postnatal day (PND) 21. At the end of exposure the pups were euthanized at PND 21 and 45 for tissue collection. A partial pendrin cDNA sequence was generated by RT-PCR. Taqman specific probe and primers were designed from this cDNA sequence for real-time PCR quantification of mRNA equivalents for pendrin gene expression. The expression profile was standardized to GAPDH. The data indicated that exposure to AP during GA and GL, significantly (p<0.05) suppressed pendrin gene expressions in the treatment groups at PND 21 and PND 45 in the ovaries. In the testes of PND 45 males following exposure to AP (58.5 ppm) during GL, pendrin gene expression was 1.5 fold higher than controls. Similar results were observed for the males of PND 45 GA exposure (117 ppm) group. The data indicates that exposure to perchlorate during GA and GL alters gene expression in the gonads of developing deer mice. This study shows that perchlorate is a potential developmental toxicant at the molecular level and raises the implication of the role of perchlorate in trans-generational effects.

Key words: deer mice, gonads, perchlorate, pendrin gene expression