EPA Science Inventory

Review of the expression of Peroxisome Proliferator Activated Receptors alpha (PPARα), beta (PPAR β), and gamma (PPAR() in rodent and human development.

Citation:

ABBOTT, B. D. Review of the expression of Peroxisome Proliferator Activated Receptors alpha (PPARα), beta (PPAR β), and gamma (PPAR() in rodent and human development. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 27(3-4):246-257, (2009).

Description:

The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear hormone receptor superfamily and there are three primary isotypes, PPARα, β, and (. These receptors regulate important physiological processes that impact lipid homeostasis, inflammation, adipogenesis, reproduction, wound healing, and carcinogenesis. These nuclear receptors have important roles in reproduction and development and their expression may influence the responses of an embryo exposed to PPAR agonists. PPARs are relevant to the study of the biological effects of the perfluorinated alkyl acids as these compounds, including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), activate the PPARα receptor. Exposure of the rodent to PFOA or PFOS during gestation results in neonatal deaths, developmental delay and growth deficits. Studies in PPARα knockout mice demonstrate that these effects depend on expression of PPARα. This review provides an overview of PPARα, β, and γ protein and mRNA expression during mouse, rat, and human development. The review presents the results from many published studies and the information is organized by organ system and collated to show patterns of expression in comparable developmental stages for human, mouse, and rat. The features of the PPAR nuclear receptor family are introduced and what is known or inferred about their roles in development is discussed relative to insights from genetically modified mice and studies in the adult.

Purpose/Objective:

Impact Statement Review of the expression of Peroxisome Proliferator Activated Receptors alpha (PPARα), beta (PPAR β), and gamma (PPARγ) in rodent and human development. Barbara D. Abbott This review supports the continuing efforts at ORD, in response to the call for assistance from OPPTS, to investigate the potential reproductive and developmental toxicities of perfluoroalkyl acids (PFAA). PPARs are relevant to the study of the biological effects the perfluoroalkyl acids as these compounds, including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), activate the PPARα receptor. Exposure of the rodent to PFOA or PFOS during gestation results in neonatal deaths, developmental delay and growth deficits. Studies in PPARα knockout mice demonstrate that the PFOA-induced developmental toxicity depends on expression of PPARα. This review provides an overview of PPARα, β, and γ protein and mRNA expression during mouse, rat, and human development. The review interprets the results from many published studies and the information is organized by organ system and collated to show patterns of expression in comparable developmental stages for human, mouse, and rat. The features of the PPAR nuclear receptor family are introduced and what is known or inferred about their roles in development is discussed relative to insights from genetically modified mice and studies in the adult.

URLs/Downloads:

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Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 06/01/2009
Completion Date: 06/01/2009
Record Last Revised: 12/03/2009
Record Created: 08/20/2008
Record Released: 08/20/2008
OMB Category: Other
Record ID: 198828

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

REPRODUCTIVE TOXICOLOGY DIVISION

DEVELOPMENTAL BIOLOGY BRANCH