Imposex development in Nucella lapillus – Evidence for the involvement of retinoid X receptor and androgen signalling pathways in vivo

Stange, Daniela; Sieratowicz, Agnes; Oehlmann, Jörg

doi:10.1016/j.aquatox.2011.10.010

Cited by 28 publications

(13 citation statements)

References 31 publications

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“…; Stange et al . ). The retinoid hypothesis suggests that organotins may mimic the endogenous ligand of RXR, disrupting the signalling pathways that are retinoic acid dependent (Castro et al .…”

Section: Introductionmentioning

confidence: 97%

Transcriptomics and in vivo tests reveal novel mechanisms underlying endocrine disruption in an ecological sentinel, Nucella lapillus

et al. 2012

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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.

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Section: Introductionmentioning

confidence: 97%

Transcriptomics and in vivo tests reveal novel mechanisms underlying endocrine disruption in an ecological sentinel, Nucella lapillus

et al. 2012

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“…Experiments in rats confirmed a regulation of rar-g by androgen signaling in several tissues [62]. Several studies suggest that there may be crosstalk between RA- and sex steroid signaling pathways during embryonic development of sexual organs or reproductive systems, e.g., in the development of imposex in gastropod females [63], the development of mammalian external genitalia [64] and sexually dimorphic anal fin, which is an electric discharge organ in electric fish [65].…”

Section: Discussionmentioning

confidence: 74%

Retinoic Acid Is Involved in the Metamorphosis of the Anal Fin into an Intromittent Organ, the Gonopodium, in the Green Swordtail (Xiphophorus hellerii)

et al. 2013

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In poeciliid fish the male anal fin has been transformed into a gonopodium, an intromittent organ required for internal fertilization. Elevated testosterone levels induce metamorphosis of a subset of anal fin rays to grow and form the specialized terminal structures of the gonopodium. The molecular mechanisms underlying these processes are largely unknown. Here, we investigated whether retinoic acid (RA) signaling is involved in gonopodium development in the swordtail Xiphophorus hellerii. We showed that aldh1a2, a RA synthesizing enzyme, and the RA receptors, rar-ga and rar-gb, are expressed in anal fins during metamorphosis. aldh1a2 expression is regulated by testosterone in a concentration-dependent manner and is up-regulated in both hormone-induced and naturally developing gonopodia. Androgen receptor (ar), a putative regulator of gonopodial development, is co-expressed with aldh1a2 and the RA receptors in gonopodial rays. Importantly, experimental increase of RA signaling promoted growth of the gonopodium and increased the number of new segments. Based on gene expression analyses and pharmacological manipulation of gonopodium development, we show that the RA signaling pathway is activated in response to androgen signaling and promotes fin ray growth and development during the metamorphosis of the anal fin into the gonopodium.

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“…In addition to binding to 9cisRA, RXR has been described as a target of endocrine disruption mediated by organotins (TBT, TPT). The induction of imposex in marine snails is a classic example of the RXR-dependent disruption by organotins at nanomolar levels [24,26,60,[62][63][64]. Furthermore, the evolutionary conservation of RXR-dependent modulation by organotins was suggested among lophotrochozoans, vertebrates, and crustaceans [27,33,65].…”

Section: Discussionmentioning

confidence: 99%

Of Retinoids and Organotins: The Evolution of the Retinoid X Receptor in Metazoa

et al. 2020

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Nuclear receptors (NRs) are transcription factors accomplishing a multiplicity of functions, essential for organismal homeostasis. Among their numerous members, the retinoid X receptor (RXR) is a central player of the endocrine system, with a singular ability to operate as a homodimer or a heterodimer with other NRs. Additionally, RXR has been found to be a critical actor in various processes of endocrine disruption resulting from the exposure to a known class of xenobiotics termed organotins (e.g., tributyltin (TBT)), including imposex in gastropod molluscs and lipid perturbation across different metazoan lineages. Thus, given its prominent physiological and endocrine role, RXR is present in the genomes of most extant metazoan species examined to date. Here, we expand on the phylogenetic distribution of RXR across the metazoan tree of life by exploring multiple next-generation sequencing projects of protostome lineages. By addressing amino acid residue conservation in combination with cell-based functional assays, we show that RXR induction by 9-cis retinoic acid (9cisRA) and TBT is conserved in more phyla than previously described. Yet, our results highlight distinct activation efficacies and alternative modes of RXR exploitation by the organotin TBT, emphasizing the need for broader species sampling to clarify the mechanistic activation of RXR.

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Imposex development in Nucella lapillus – Evidence for the involvement of retinoid X receptor and androgen signalling pathways in vivo

Cited by 28 publications

References 31 publications

Transcriptomics and in vivo tests reveal novel mechanisms underlying endocrine disruption in an ecological sentinel, Nucella lapillus

Transcriptomics and in vivo tests reveal novel mechanisms underlying endocrine disruption in an ecological sentinel, Nucella lapillus

Retinoic Acid Is Involved in the Metamorphosis of the Anal Fin into an Intromittent Organ, the Gonopodium, in the Green Swordtail (Xiphophorus hellerii)

Of Retinoids and Organotins: The Evolution of the Retinoid X Receptor in Metazoa

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