The utility of vitellogenin as a biomarker of estrogenic endocrine disrupting chemicals in molluscs

Estrogenic endocrine disrupting chemicals (EDCs) are natural hormones, synthetic compounds or industrial chemicals that mimic estrogens due to their structural similarity with estrogen's functional moieties. They typically enter aquatic environments through wastewater treatment plant effluents or runoff from intensive livestock operations. Globally, most natural and synthetic estrogens in receiving aquatic environments are in the low ng/L range, while industrial chemicals (such as bisphenol A, nonylphenol and octylphenol) are present in the μg to low mg/L range. These environmental concentrations often exceed laboratory-based predicted no effect concentrations (PNECs) and have been evidenced to cause negative reproductive impacts on resident aquatic biota. In vertebrates, such as fish, a well-established indicator of estrogen-mediated endocrine disruption is overexpression of the egg yolk protein precursor vitellogenin (Vtg) in males. Although the vertebrate Vtg has high sensitivity and specificity to estrogens, and the molecular basis of its estrogen inducibility has been well studied, there is growing ethical concern over the use of vertebrate animals for contaminant monitoring. The potential utility of the invertebrate Vtg as a biomonitor for environmental estrogens has therefore gained increasing attention. Here we review evidence providing support that the molluscan Vtg holds promise as an invertebrate biomarker for exposure to estrogens. Unlike vertebrates, estrogen signalling in invertebrates remains largely unclarified and the classical genomic pathway only partially explains estrogen-mediated activation of Vtg. In light of this, in the latter part of this review, we summarise recent progress towards understanding the molecular mechanisms underlying the activation of the molluscan Vtg gene by estrogens and present a hypothetical model of the interplay between genomic and non-genomic pathways in the transcriptional regulation of the gene.