The retinoic acid receptor (RAR) in molluscs: Function, evolution and endocrine disruption insights

André, Ana; Ruivo, Raquel; Fonseca, Elza; Froufe, Elsa; Castro, L. Filipe C.; Santos, Miguel M.

doi:10.1016/j.aquatox.2019.01.002

Cited by 21 publications

(26 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the various hormones involved (thyroid hormones, insulin, Growth hormone (GH) variants, leptin, cortisol) a key role is played by Insulin-like growth Factor (IGF)-1 and IGF-2 [2], and it is important to cite (see the following chapters) that the inflammatory and the IGF systems also interact [3]. In recent years, additional factors were discovered and proved to be of upmost importance [4][5][6] such as Activin, A.; Human corionic gonadotropin (HCG), and retinoic acid and its receptors in animal models [7].…”

Section: Introductionmentioning

confidence: 99%

Endocrine-Disrupting Chemicals in Human Fetal Growth

Street

Bernasconi

2020

IJMS

111

View full text Add to dashboard Cite

Fetal growth is regulated by a complex interaction of maternal, placental, and fetal factors. The effects and outcomes that chemicals, widely distributed in the environment, may have on the health status of both the mother and the fetus are not yet well defined. Mainly mixtures of chemical substances are found in the mothers and placenta. Exposure to endocrine-disrupting chemicals (EDCs) can be associated with fetal growth retardation, thyroid dysfunction, and neurological disorders. EDCs mostly interfere with insulin, glucocorticoid, estrogenic, and thyroid pathways, with subsequent effects on normal endocrine and metabolic functions, which cause changes in the epigenome and state of inflammation with life-long effects and consequences. International scientific societies recommend the implementation of research and of all possible preventive measures. This review briefly summarizes all these aspects.

show abstract

Section: Introductionmentioning

confidence: 99%

Endocrine-Disrupting Chemicals in Human Fetal Growth

Street

Bernasconi

2020

IJMS

111

View full text Add to dashboard Cite

show abstract

“…The search for RAR gene orthologues in Ecdysozoa (e.g., arthropods and nematodes) genomes was previously unsuccessful, implying that RAR was probably lost in this superphylum [15]. Overall, these studies suggest that 1) RAR evolution was shaped by events of secondary gene loss during Bilateria evolution, notably in the whole Ecdysozoa lineage and Appendicularia (Tunicata) [15,16,18] and 2) the bilaterian RAR ancestor was a RA low-affinity sensor, with the ability to bind retinoids and activate transcription of target genes-annelids (Platynereis), or a receptor without capacity to bind ligands as seen in molluscs [22][23][24][25]. Additionally, NRs are prime targets of endocrine disrupting chemicals (EDCs) (e.g., [27]), with various examples denoting the impact of EDCs acting via NRs [28,29].…”

Section: Introductionmentioning

confidence: 86%

“…Recently, RAR was also functionally characterized in various mollusc species and in a second Lophotrochozoa clade, the annelid worm Platynereis dumerilii. Yet, functional studies in mollusc species demonstrated the loss of RA binding affinity towards RAR [21][22][23][24]. In contrast, the annelid Platynereis RAR orthologue showed a conserved capacity to bind and respond to retinoids, but with lower affinity compared to vertebrate RAR paralogues [25].…”

Section: Introductionmentioning

confidence: 99%

“…Yet, variations in NR gene complement and sequence variation as well as the molecular architecture of endocrine systems are of paramount importance to recognize the mechanisms of action of EDCs [30,31], particularly in invertebrate lineages, e.g., [32,33]. In the specific case of RAR, environmental contaminants such as pesticides have been shown to exploit mammalian RARs [34], but not the molluscan orthologue [24]. To further scrutinize the evolution RA signalling, specifically if RAR is absent or present in other extant Ecdysozoa lineages, we investigated the genome of the penis worm, Priapulus caudatus Lamarck, 1816 (Scalidophora, Priapulida).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Orthologue of the Retinoic Acid Receptor (RAR) Is Present in the Ecdysozoa Phylum Priapulida

Fonseca

Hiromori

Kaite

et al. 2019

Genes

Self Cite

View full text Add to dashboard Cite

Signalling molecules and their cognate receptors are central components of the Metazoa endocrine system. Defining their presence or absence in extant animal lineages is critical to accurately devise evolutionary patterns, physiological shifts and the impact of endocrine disrupting chemicals. Here, we address the evolution of retinoic acid (RA) signalling in the Priapulida worm, Priapulus caudatus Lamarck, 1816, an Ecdysozoa. RA signalling has been shown to be central to chordate endocrine homeostasis, participating in multiple developmental and physiological processes. Priapulids, with their slow rate of molecular evolution and phylogenetic position, represent a key taxon to investigate the early phases of Ecdysozoa evolution. By exploring a draft genome assembly, we show, by means of phylogenetics and functional assays, that an orthologue of the nuclear receptor retinoic acid receptor (RAR) subfamily, a central mediator of RA signalling, is present in Ecdysozoa, contrary to previous perception. We further demonstrate that the Priapulida RAR displays low-affinity for retinoids (similar to annelids), and is not responsive to common endocrine disruptors acting via RAR. Our findings provide a timeline for RA signalling evolution in the Bilateria and give support to the hypothesis that the increase in RA affinity towards RAR is a late acquisition in the evolution of the Metazoa.

show abstract

“…These compounds serve as a significant example, with TBT-dependent activation of gastropod mollusc RXRs suggested as the prime cause of imposex development [24,26]. TBT ability to induce RXR-dependent transcription was demonstrated in human, mollusc, annelid, and crustacean RXRs and seems reliant on the presence of a specific cysteine residue within the ligand-binding domain (LBD) [24,27,33,[42][43][44].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

The retinoic acid receptor (RAR) in molluscs: Function, evolution and endocrine disruption insights

Cited by 21 publications

References 83 publications

Endocrine-Disrupting Chemicals in Human Fetal Growth

Endocrine-Disrupting Chemicals in Human Fetal Growth

An Orthologue of the Retinoic Acid Receptor (RAR) Is Present in the Ecdysozoa Phylum Priapulida

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

Contact Info

Product

Resources

About