Impairments of Endocrine Functions: Causes and Consequences - Ecological Biomarkers: Indicators of Ecotoxicological Effects - page 204

forms, likely to be a target of pollutants. For instance, some studies have shown the abil-
ity of endocrine disruptors to alter steroid metabolism in invertebrates and particularly in
mollusks. In vitro studies have shown that TBT inhibited aromatase activity in the bivalves
Ruditapes decussata and Crassostrea gigas (Morcillo et al. 1998; Le Curieux-Belfond et al. 2001).
Exposure to TBT also decreased testosterone sulfation and testosterone esterification in
Littorina littorea (Ronis and Mason 1996) and the mudsnail IIyanassa obsoleta (Gooding et al.
2003). Steroid levels were also impaired in the mudsnail Potamopyrgus antipodarum exposed
to the specific vertebrate aromatase inhibitor, fadrozole (Gust et al. 2010b).
In vertebrates, the effects of steroids are mediated by intracellular or cell surface recep-
tors. In recent studies, ER orthologs were identified in several mollusks, e.g., Aplysia cali-
fornica (Thornton et al. 2003), Thais clavigera (Kajiwara et al. 2006), Octopus vulgaris (Keay et
al. 2006), C. gigas (Matsumoto et al. 2007), Marisa cornuarietis (Bannister et al. 2007), Nucella
lapillus (Castro et al. 2007), and P. antipodarum (Stange et al. 2012), but these receptors seem
to be constitutively active without the ability of estrogen binding.
An alternative candidate hormone signaling pathway is retinoic acid acting via the
RXR. Several studies provide substantial evidence that the retinoid signaling pathway
is involved in reproductive development and is the target through which TBT causes
imposex (Sternberg et al. 2008). Other hypotheses could be that the active molluscan sex
hormone is not E2 itself, but a derivate (Baker 2004; Paris et al. 2008b), or that a receptor,
capable of E2 binding, has not still been identified.
Moreover, besides the “classical” genomic pathway, recent studies have shown that E2
can act through nongenomic mechanisms (reviewed by Janer and Porte 2007) in mollusks
causing rapid effects. These alternative pathways of EDCs can involve membrane ERs or
receptor-independent mechanisms, with possible both direct local effect (such as modula-
tion of ion fluxes) and regulation of gene transcription secondary to modulation of kinase
cascades, and are likely to impair functions other than reproduction, such as, in particular,
immune function (Stefano et al. 2003; Canesi et al. 2004).
Results suggest that synthesis of VTG-like protein occurs in bivalve gonads (Li et al.
1998; Matsumoto et al. 2003) under control of both estrogen and neuropeptides (Osada
et al. 2003). Similar to fish, VTG-like protein measurements have been used to assess the
effect of potential xenoestrogens in bivalves, by using mainly indirect methods such as
use of ALPs both in laboratory and field studies (review of Matozzo et al. 2007; Porte et al.
2006). Gagné et al. (2002) showed modifications in VTG-like proteins of bivalves exposed to
polluted environments, prompting interest in the study of VTG-like proteins in bivalves.
Nevertheless, knowledge on the functioning of the molluscan endocrine system and its
role in controlling reproduction remains insufficient, and, except for the presence or degree
of imposex in gastropods, no biomarker is yet available in mollusks to clearly identify endo-
crine disruption likely to have been caused by environmental exposure to xenoestrogens.
8.7 Ecological Consequences of Endocrine Disruption
Field and experimental studies at environmentally relevant concentrations (e.g., Li et al.
2011; Sarria et al. 2011; Hatef et al. 2012) have established that EDCs represent a serious threat
for the future of our environment. In 2005, Mills and Chichester considered that linking
endocrine disruption and reproductive impairment with an ecologically relevant impact
on the sustainability of real fish populations remained an open challenge. Weis et al. (2011)