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Published on: December 14, 2014
Hepatic Transcriptomic Patterns in the Neonatal Rat After Pentabromodiphenyl Ether Exposure
June K Dunnick1, Keith R Shockley2, Daniel L Morgan1
1Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Insights
Neonatal exposure to PBDEs like DE-71 and PBDE-47 alters rat liver gene expression, indicating potential toxicity and carcinogenicity. These early transcriptomic changes serve as crucial indicators for risk assessment.
Area of Science:
- Toxicology
- Environmental Health
- Genomics
Background:
- Human exposure to polybrominated diphenyl ethers (PBDEs) occurs in utero and during lactation.
- PBDEs are flame retardants with potential health risks.
Purpose of the Study:
- To investigate if neonatal hepatic transcriptomic alterations from PBDE exposure predict longer-term toxicity and carcinogenicity.
- To assess the utility of early toxicogenomic indicators for risk evaluation.
Main Methods:
- Wistar Han rat dams were exposed to DE-71 or PBDE-47 from gestation day 6 to postnatal day 4.
- Hepatic gene expression and plasma thyroxine (T4) levels were analyzed in pups.
Main Results:
- Decreased plasma T4 levels were observed in exposed pups.
- Upregulation of transcripts for CYPs, conjugation enzymes, Nrf2, and ABC transporters in the liver.
- Transcriptomic alterations indicated early signs of oxidative stress and metabolic changes.
Conclusions:
- Neonatal PBDE exposure induces hepatic transcriptomic changes that serve as early indicators of potential toxicity and carcinogenicity.
- PBDE-47 showed a lower transcriptional benchmark dose than the PBDE mixture.
- Toxicogenomic data can help prioritize chemicals for further risk assessment.
Abstract:
Human exposure to pentabromodiphenyl ether (PBDE) mixture (DE-71) and its PBDE-47 congener can occur both in utero and during lactation. Here, we tested the hypothesis that PBDE-induced neonatal hepatic transcriptomic alterations in Wistar Han rat pups can inform on potential toxicity and carcinogenicity after longer term PBDE exposures. Wistar Han rat dams were exposed to either DE-71 or PBDE-47 daily from gestation day (GD 6) through postnatal day 4 (PND 4). Total plasma thyroxine (T4) was decreased in PND 4 pups. In liver, transcripts for CYPs and conjugation enzymes, Nrf2, and ABC transporters were upregulated. In general, the hepatic transcriptomic alterations after exposure to DE-71 or PBDE-47 were similar and provided early indicators of oxidative stress and metabolic alterations, key characteristics of toxicity processes. The transcriptional benchmark dose lower confidence limits of the most sensitive biological processes were lower for PBDE-47 than for the PBDE mixture. Neonatal rat liver transcriptomic data provide early indicators on molecular pathway alterations that may lead to toxicity and/or carcinogenicity if the exposures continue for longer durations. These early toxicogenomic indicators may be used to help prioritize chemicals for a more complete toxicity and cancer risk evaluation.
