Application of Ecotoxicogenomics for Studying Endocrine Disruption in Vertebrates and Invertebrates

Abstract

Chemicals released into the environment potentially disrupt the endocrine system in wild animals and humans. Developing organisms are particularly sensitive to estrogenic chemicals. Exposure to estrogens or estrogenic chemicals during critical periods of development induces persistent changes in both reproductive and nonreproductive organs, including persistent molecular alterations. Estrogen-responsive genes and critical developmental windows of various animal species, therefore, need to be identified for investigators to understand the molecular basis of estrogenic activity during embryonic development. For investigators to understand molecular mechanisms of toxicity in various species, toxicogenomics/ecotoxicogenomics, defined as the integration of genomics (transcriptomics, proteomics, metabolomics) into toxicology and ecotoxicology, need to be established as powerful tools for research. As the initial step toward using genomics to examine endocrine-disrupting chemicals, estrogen receptors and other steroid hormone receptors have been cloned in various species, including reptiles, amphibians, and fish, and alterations in the expression of these genes in response to chemicals were investigated. We are identifying estrogen-responsive genes in mouse reproductive tracts using cDNA microarrays and trying to establish microarray systems in the American alligator, roach, medaka, and water fleas (Daphnia magna). It is too early to define common estrogen-responsive genes in various animal species; however, toxicogenomics and ectotoxicogenomics provide powerful tools to help us understand the molecular mechanism of chemical toxicities in various animal species.

Cell Growth of Ovarian Cancer Cells is Stimulated by Xenoestrogens through an Estrogen-Dependent Pathway, but Their Stimulation of Cell Growth Appears not to be Involved in the Activation of the Mitogen-Activated Protein Kinases ERK-1 and p38

“…In addition, it has been reported that endocrine disrupting chemicals (EDCs) may increase the risk of cancer incidence [3,4]. However, the data associated with the effect of EDCs on ovarian cancer cells are scarce.Since EDCs are known as environmental chemicals that interfere with the hormonal balance of vertebrates and invertebrates, they are considered to be important in physiology and the endocrine system [5,6]. EDCs are released from industrial products such as plastics, pesticides, detergents and other synthetic products.…”

“…In addition, 4-alkylphenol ethoxylates (APEs) are widely used as surfactants in lubricant oil addictives, phosphate antioxidants and rubber products [15], and they have been shown to have an estrogenic effect [16]. Furthermore, the metabolites of APEs, such as nonylphenol (NP) and octylphenol (OP), exhibit an estrogenic effect at low concentrations [5,17]. They are known as toxic contaminants and can be found in indoor/outdoor air and in the aquatic environment [18,19].…”

Adverse outcome pathways and ecological risk assessment: Bridging to population‐level effects

“…However, the precise biochemical cause of imposex is poorly characterized [65,66]. Although bis(tri-n-butyltin) apparently inhibits aromatase, limiting the conversion of testosterone to E 2 [67], whether all species subject to imposex express a functional estrogen receptor [68], suggesting that estrogens may not have a causal role in the development of imposex, is unknown. A new linkage has been proposed between imposex and the retinoid-X-receptor, a member of the nuclear hormone receptor superfamily for which the natural ligand is 9-cis-retinoic acid.…”

Effects of adrenergic agents on the expression of zebrafish (Danio rerio) vitellogenin Ao1

“…Thus, some in vivo test methods, that are based on definitive indicators and could detect and assess estrogenic effects of xenobiotics and wastewater in fishes, have been suggested (Tyler et al, 1996;Huchinson et al, 2006). Among the methods, vitellogenin (VTG) is one of the most frequently used in vivo and in vitro biomarkers for estrogenicity in fish (Hutchinson et al, 2000;Waring and Harris, 2005;Iguchi et al, 2006). Fish VTGs are usually considered to be the precursors of major egg yolk proteins.…”

“…However, they can be readily induced by exposure to exogenous estrogenic compounds. As the production of VTGs is usually considered estrogen-dependent, VTG induction is normally considered as a response specific for estrogens and has been considered to be a valuable bioindicator for monitoring estrogenic contamination of aquatic environments (Hutchinson et al, 2000;Waring et al, 2005;Iguchi et al, 2006;Jensen and Ankley, 2006;Miller et al, 2007). However, the physiological functions and the regulation of VTG expression in fish have not been explored in detail.…”