Estrogenic compounds as exogenous modulators of physiological functions in molluscs: Signaling pathways and...

Molluscs have been widely utilized to evaluate the effects of estrogenic compounds, one of the most widespread classes of Endocrine Disrupting Chemicals-EDCs. However, knowledge on steroid signaling and metabolism in molluscs has considerably increased in the last decade: from these studies, a considerable debate emerged on the role of 'natural' steroids in physiology, in particular in reproduction, of this invertebrate group. In this work, available information on the effects and mechanisms of action of estrogens in molluscs will be reviewed, with particular emphasis on bivalves that, widespread in aquatic ecosystems, are most likely affected by exposure to estrogenic EDCs. Recent advances in steroid uptake and metabolism, and estrogen receptors-ERs in molluscs, as well as in estrogen signaling in vertebrates, will be considered. The results so far obtained with 17β-estradiol and different estrogenic compounds in the model bivalve Mytilus spp., demonstrate specific effects on immune function, development and metabolism. Transcriptomic data reveal non genomic estrogen signaling pathways in mussel tissues that are supported by new observations at the cellular level. In vitro and in vivo data show, through independent lines of evidence, that estrogens act through non-genomic signaling pathways in bivalves. In this light, regardless of whether molluscs synthesize estrogens de novo or not, and despite their ERs are not directly activated by ligand binding, estrogens can interact with multiple signaling components, leading to modulation of different physiological functions. Increasing knowledge in endocrine physiology of molluscs will provide a framework for a better evaluation and interpretation of data on the impact of estrogenic EDCs in this invertebrate group.