Disruption of Retinoic Acid Receptor Signaling by Environmental Pollutants

Retinoic acid (RA) receptors (RARs) are nuclear receptors that play a critical role in regulating cellular proliferation, development and differentiation in vertebrates in response to endogenous RAs, i.e., all-trans RA and 9-cis RA. On the other hand, it has been well-known that both a deficiency and an excess of RA and related retinoids can cause a variety of teratogenic effects on developing embryos of vertebrates, which has been proven to be an RAR-mediated process. Therefore, the occurrence of xenobiotic environmental pollutants that interfere with RARs and disrupt the RAR signaling (i.e., show RAR agonistic or antagonistic effects) may pose a threat to the health of wild animals and humans. This review mainly focuses on RAR agonists. We summarize the RAR agonistic activity of natural and xenobiotic compounds determined using in vitro bioassay systems and present recent field research showing the occurrence of RAR agonist contamination in the aquatic environment in North America, China and Japan. Environmental pollution by RAR agonists is a new endocrine disruption issue discovered very recently, and relevant knowledge is very limited. Further research will be required to obtain accurate information to assess the possible risks of RAR agonists in the environment.