INVESTIGATING THE EFFECTS OF GESTATIONAL EXPOSURE TO THE FLAME RETARDANT, TRIPHENYL PHOSPHATE, ON MATERNAL LIVER IN C57BL/6 MICE
Restivo, Victoria E.
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Due to the recent banning of polybrominated diphenyl ethers (PBDE), the use of other flame retardants has increased, including triphenyl phosphate (TPP), an organophosphate ester flame retardant, which is contained in many consumer and industry products. As such, there is widespread exposure to TPP globally, including pregnant women. At present, data and knowledge surrounding the toxicological effects of TPP is limited, but some studies suggest endocrine and metabolic disrupting effects. In this study we examined the effects of gestational exposure to TPP (0, 5, 25, and 50 mg/kg on gestational day 8, 10, 12, and 14 via intraperitoneal injection) on the maternal liver of C57BL/6 mice through analysis of mRNA expression of genes involved in the insulin-like growth factor (Igf) 1 signaling pathway, including Igf1, its receptor, Igf1r, and downstream signaling proteins: insulin receptor substrates (Irs) 1 and 2 along with expression of peroxisome proliferator-activated receptor alpha (Ppar-α), a gene important in glucose and lipid metabolism, and carboxylesterase (CE) activity, an enzyme important in lipolysis and lipid metabolism. Using quantitative real-time PCR we determined that exposure to TPP resulted in no significant changes in the expression of Igf-1r, Irs-1, and Ppar-α. However, there was a significant decrease in the mRNA expression of Igf-1 and Irs-2. These findings suggest that gestational exposure to TPP may cause toxic endocrine and metabolic disrupting effects. Based on these findings, further studies are warranted to examine the associations between widespread TPP exposure and levels of Igf-1, Igf-1r, Irs-1, Irs-2, and Ppar-α in the potential development of maternal and fetal toxicity. Additionally, a CE activity assay was conducted with no significant changes observed between TPP treatment groups. Taken together, these results suggest that TPP may alter mRNA expression of genes and further research is required into the effect of TPP on both mRNA expression and CE activity.