title: Transcriptomics and in vivo tests reveal novel mechanisms underlying endocrine disruption in an ecological sentinel, Nucella lapillus.
abstract: Anthropogenic endocrine disruptors now contaminate all environments globally, with concomitant deleterious effects across diverse taxa. While most studies on endocrine disruption (ED) have focused on vertebrates, the superimposition of male sexual characteristics in the female dogwhelk, Nucella lapillus (imposex), caused by organotins, provides one of the most clearcut ecological examples of anthropogenically induced ED in aquatic ecosystems. To identify the underpinning mechanisms of imposex for this 'nonmodel' species, we combined Roche 454 pyrosequencing with custom oligoarray fabrication inexpensively to both generate gene models and identify those responding to chronic tributyltin (TBT) treatment. The results supported the involvement of steroid, neuroendocrine peptide hormone dysfunction and retinoid mechanisms, but suggested additionally the involvement of putative peroxisome proliferator-activated receptor (PPAR) pathways. Application of rosiglitazone, a well-known vertebrate PPARγ ligand, to dogwhelks induced imposex in the absence of TBT. Thus, while TBT-induced imposex is linked to the induction of many genes and has a complex phenotype, it is likely also to be driven by PPAR-responsive pathways, hitherto not described in invertebrates. Our findings provide further evidence for a common signalling pathway between invertebrate and vertebrate species that has previously been overlooked in the study of endocrine disruption.
authors.affiliation: Molecular Ecology and Fisheries Genetics Laboratory, Environment Centre Wales, School of Biological Sciences, Bangor University, Gwynedd, LL57 2UW, UK.
authors.forename: Sonia
authors.initials: S
authors.lastname: Pascoal
authors.forename: Gary
authors.initials: G
authors.lastname: Carvalho
authors.forename: Olga
authors.initials: O
authors.lastname: Vasieva
authors.forename: Roger
authors.initials: R
authors.lastname: Hughes
authors.forename: Andrew
authors.initials: A
authors.lastname: Cossins
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Fang
authors.forename: Kevin
authors.initials: K
authors.lastname: Ashelford
authors.forename: Lisa
authors.initials: L
authors.lastname: Olohan
authors.forename: Carlos
authors.initials: C
authors.lastname: Barroso
authors.forename: Sonia
authors.initials: S
authors.lastname: Mendo
authors.forename: Simon
authors.initials: S
authors.lastname: Creer
mesh_terms: D000818:Animals; D012734:Disorders of Sex Development / Q000139:chemically induced*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D049851:Gastropoda / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015723:Gene Library; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D000077154:Rosiglitazone; D017422:Sequence Analysis, DNA; D045162:Thiazolidinediones / Q000633:toxicity; D059467:Transcriptome; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D052244:Endocrine Disruptors; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D014220:Trialkyltin Compounds; D014874:Water Pollutants, Chemical; D000077154:Rosiglitazone; C011559:tributyltin