Abbott Barbara D
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
Reprod Toxicol. 2009 Jun;27(3-4):246-257. doi: 10.1016/j.reprotox.2008.10.001. Epub 2008 Oct 18.
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear hormone receptor superfamily and there are three primary subtypes, PPARalpha, beta, and gamma. 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 PPARalpha. Exposure of the rodent to PFOA or PFOS during gestation results in neonatal deaths, developmental delay and growth deficits. Studies in PPARalpha knockout mice demonstrate that the developmental effects of PFOA, but not PFOS, depend on expression of PPARalpha. This review provides an overview of PPARalpha, beta, and gamma 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 at 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.
过氧化物酶体增殖物激活受体（PPAR）属于核激素受体超家族，主要有三种亚型，即PPARα、β和γ。这些受体调节着影响脂质稳态、炎症、脂肪生成、生殖、伤口愈合和致癌作用的重要生理过程。这些核受体在生殖和发育中发挥着重要作用，其表达可能会影响暴露于PPAR激动剂的胚胎的反应。PPAR与全氟烷基酸的生物学效应研究相关，因为这些化合物，包括全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS），可激活PPARα。啮齿动物在妊娠期接触PFOA或PFOS会导致新生儿死亡、发育迟缓以及生长缺陷。对PPARα基因敲除小鼠的研究表明，PFOA而非PFOS的发育效应取决于PPARα的表达。本综述概述了小鼠、大鼠和人类发育过程中PPARα、β和γ蛋白及mRNA的表达情况。该综述呈现了许多已发表研究的结果，信息按器官系统进行整理，以展示人类、小鼠和大鼠在可比发育阶段的表达模式。文中介绍了PPAR核受体家族的特征，并结合基因敲除小鼠的研究结果及成年动物研究的见解，讨论了其在发育过程中已知或推测的作用。
