Bisphenol A affects neural development of the ascidian Ciona robusta

Abstract

Bisphenol A (BPA) is an organic pollutant derived from plastic degradation that has numerous and variable adverse effects on human health and wildlife. In particular, it has been reported that BPA can alter reproductive processes and nervous system development in vertebrates. Considering BPA presence in marine environment and the scant data available on its interaction with nervous system development, we analyzed the effect of BPA exposure on sperm viability, fertilization, embryogenesis, and neural differentiation of the ascidian Ciona robusta. Ascidians are members of the Phylum Tunicata, the sister group of Vertebrata, sharing with them fundamental developmental processes. Our results showed that first cell division was altered starting from 5 µM concentration. Lethal concentration (LC ) was estimated to be 5.2 µM. Larvae developed from treated embryos showed specific malformations to the pigment cells even at 0.1 µM, corresponding to the highest environmental concentration reported so far. Moreover, GABAergic and dopaminergic neurons proved to be target organs of BPA teratogenic action, in accordance with similar results reported in vertebrate animal models. Overall, our results suggest that BPA can exert its effects on nervous system acting on different pathways and underline that C. robusta is a valuable invertebrate animal model for preliminary screenings of effects of pollutants on vertebrates.

Potential roles of nuclear receptors in mediating neurodevelopmental toxicity of known endocrine‐disrupting chemicals in ascidian embryos

“…At sublethal doses, BPA has been shown to delay larval development in copepods and molluscs, to induce changes in immune digestive gland function in marine bivalves, or to stimulate metamorphosis and larval development in marine polychaetes and copepods (Canesi & Fabbri, ), with effective concentrations ranging from 0.01 up to 300 µg/µl (Flint et al, ). Furthermore, BPA and other known vertebrate EDCs, such as diuron and diethylstilbestrol specifically affect neurodevelopment in ascidians at low doses, as recently reported (Dumollard, Gazo, Gomes, Besnardeau, & McDougall, ; Messinetti, Mercurio, & Pennati, ; Messinetti, Mercurio, & Pennati, ). However, apart from the phenotypes and dose‐response sensitivity, few studies assessed the mode‐of‐action and even fewer addressed the potential involvement of NRs in the teratogenic effects of EDCs in marine invertebrates.…”

Effects of bisphenol A on the development of pigmented organs in the ascidian Phallusia mammillata

“…4‐OHT is an inverse agonist of human ERRγ that is known to decrease the constitutive activity of the receptor (Coward, Lee, Hull, & Lehmann, ). Alterations of sensory organs induced by BPA were also observed in the ascidians Ciona robusta (Messinetti, Mercurio, & Pennati, ) and Phallusia mammilata (Dumollard, Gazo, Gomes, Besnardeau, & McDougall, ).…”

“…In ascidians, previous studies conducted on Ciona intestinalis and C. robusta (Cangialosi, Mansueto, & Faqi, ; Matsushima, Ryan, Shimohigashi, & Meinertzhagen, ; Messinetti et al., ) reported various effects of BPA on developmental processes. In the present work, we explored the ontogenetic impairments induced by BPA in another ascidian species, P. mammillata .…”

“…When the exposure occurred after the first cell division, embryos of P. mammillata could reach the larval stage in the presence of BPA, even at the highest tested concentration of 20 μM BPA, although all larvae were malformed. By contrast, in C. robusta , 20 μM BPA was lethal (Messinetti et al., ), suggesting that differences in the tolerance to BPA action are also common in these marine invertebrates. Immunostaining with anti‐β‐tubulin showed an alteration of neural fiber pattern in P. mammillata , comparable to that observed in C. robusta .…”

Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids

“…Standard in situ hybridizations with riboprobes were performed [61]. To characterize the effects of PNA injections, the following neural marker genes were employed: Ci-Pans [37], Ci-POU IV [38], and Ci-V-Glut [39].…”