Effects of Tributyltin and Other Retinoid Receptor Agonists in Reproductive-Related Endpoints in the Zebrafish (Danio rerio)

Abstract

Both field and experimental data examined the influence of exposure to environmental contaminant tributyltin (TBT) on marine organisms. Although most attention focused on the imposex phenomenon in gastropods, adverse effects were also observed in other taxonomic groups. It has been shown that imposex induction involves modulation of retinoid signaling in gastropods. Whether TBT influences similar pathways in fish is yet to be addressed. In this study, larvae of the model teleost Danio rerio were exposed to natural retinoids, all-trans-retinoic acid, 9-cis-retinoic acid, and all-trans-retinol, as well as to the RXR synthetic pan-agonist methoprene acid (MA) and to TBT. Larvae were exposed to TBT from 5 days post fertilization (dpf) to adulthood, and reproductive capacity was assessed and correlated with mode of action. TBT significantly decreased fecundity at environmentally relevant levels at 1 μg TBT Sn/g in diet. Interestingly, in contrast to previous reports, TBT altered zebrafish sex ratio toward females, whereas MA exposure biased sex toward males. Since fecundity was significantly altered in the TBT-exposed group with up to 62% decrease, the potentially affected pathways were investigated. Significant downregulation was observed in brain mRNA levels of aromatase b (CYP19a1b) in females and peroxisome proliferator activated receptor gamma (PPARg) in both males and females, suggesting an involvement of these pathways in reproductive impairment associated with TBT.

The Role of Peroxisome Proliferator-Activated Receptor Gamma (PPARG) in Adipogenesis: Applying Knowledge from the Fish Aquaculture Industry to Biomedical Research

“…Importantly, zebrafish pparg mRNA is detected in adipocytes (56, 58, 60). Moreover, many compounds known to stimulate mammalian Pparg also modulate zebrafish pparg mRNA; including, organotin compounds such as tributyltin (63, 64), halogenated analogs of bisphenol A (65), and PGJ(2) (66). Construction of a zebrafish transgenic line expressing the human PPARG LBD fused to a Gal4 DBD exhibits increased transcriptional activity after treatment with TZDs including rosiglitazone, pioglitazone, or troglitazone (67), thus suggesting that ligand-dependent coactivators of Pparg are conserved and functional in zebrafish.…”

Gold nanorods induce early embryonic developmental delay and lethality in zebrafish (Danio rerio)

“…Zebrafish embryos were selected since this species is recognized as a suitable and relevant model for ecotoxicological studies, with a high degree of genetic, molecular, and physiological similarity to humans and a good alternative to animal testing (Dai et al, 2014;Dooley & Zon, 2000;Lima et al, 2015;Lyche et al, 2016;Weber et al, 2015). The Au content of zebrafish embryos exposed to CTAB-AuNR was measured prior to and shortly after hatching to determine internalization of these NR.…”

Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice

“…For example, organotins, in particular tributyltin (TBT), largely used as antifouling agents in paints and in many industrial processes, can promote obesity by activating peroxisome proliferator‐activated receptor γ (PPARγ) and retinoid X receptor (RXRα, RXRβ, and RXRγ), that induces in vitro differentiation of pre‐adipocytes to adipocytes, while in vivo can lead to an increase in body fat storage (for a recent review see Grun, ). The wide distribution and the high persistence of TBT in fresh and salt water have raised concern about its adverse effects on animal (in particular marine invertebrates and fishes, Leung et al ., ; Lima et al ., ) and human health (Rantakokko et al ., , ).…”