Endocrine-immune interactions and the immunotoxicity of endocrine disrupting chemicals in rainbow trout (Oncorhynchus mykiss)

The immune system of fish provides a critical barrier to protect against infectious diseases caused by pathogens in the environment. It is known that the endocrine system can modulate immune function in fish, as can exposure to xenobiotics present in the aquatic environment. The overarching objective of the five studies presented here was to investigate the effects of endocrine hormones (17β-estradiol (E2), cortisol) and endocrine disrupting pesticides and formulants (nonylphenol, atrazine, permethrin, piperonyl butoxide, chlorothalonil, pentachlorophenol and cypermethrin) on immune function in juvenile rainbow trout (Oncorhynchus mykiss) using comprehensive panels of immune function assays at multiple levels of biological organization. In addition, the use of functional assays in combination with genomic techniques (quantitative polymerase chain reaction, QPCR; microarrays) was intended to elucidate some of the mechanisms through which immunotoxic effects may be occurring. Following confirmation that all 4 forms of rainbow trout estrogen receptor (ERs) mRNA was present in leukocytes, it was found that exposure of leukocytes to lipopolysaccharide (a mitogen that stimulates cellular proliferation) led to down-regulation of both ERα1 and ERα2, suggesting a role for the ER (and E2) in cell cycle control and proliferation. Exposure of fish to exogenous E2 (in water) led to several alterations in lymphocyte function, as well as differentially regulating the transcription of both ERα1 and ERα2 in leukocytes. It was also found that all of the pesticides or formulants tested, except cypermethrin, were immunotoxic or cytotoxic and may pose a risk to fish health. Nonylphenol and atrazine exposure increased disease susceptibility, and microarray analysis of liver from exposed fish showed that a broad range of immune-related functions were altered at the molecular level. Overall, the studies detailed here provide new insight (e.g. presence of ER mRNA in leukocytes, microarray data analysis revealing affected biological processes and pathways) into potential mechanisms underlying the immunomodulatory effects of both endocrine hormones and endocrine disrupting pesticides. Since many of the immunotoxic effects of pesticide or formulant exposure occurred at environmentally relevant concentrations, these chemicals may pose a risk to the immunological health of wild fish populations living in impacted aquatic environments.