An adverse outcome pathway approach linking retinoid signaling disruption to teratogenicity and population-level outcomes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F24%3A00138643" target="_blank" >RIV/00216224:14310/24:00138643 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0166445X24003138?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0166445X24003138?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.aquatox.2024.107143" target="_blank" >10.1016/j.aquatox.2024.107143</a>

Result language

angličtina

Original language name

An adverse outcome pathway approach linking retinoid signaling disruption to teratogenicity and population-level outcomes

Original language description

Recent research efforts in endocrine disruption have focused on evaluating non-EATS (estrogen, androgen, thyroid, and steroidogenesis) pathways. Retinoid signaling disruption is noteworthy because of its teratogenic effects and environmental relevance. However, current environmental risk assessments are limited in their ability to evaluate impacts on individuals and populations. This study characterizes an Adverse Outcome Pathway (AOP) network linking retinoid signaling disruption to teratogenicity and survival in zebrafish. We identified Retinoic Acid Receptor (RAR) overactivation as the molecular initiating event leading to key events including craniofacial (CFM) and tail (TM) malformations, posterior swim bladder (SB) non-inflation, impaired swimming performance, and reduced feeding, ultimately resulting in decreased survival. Our study (1) determines critical sensitivity windows for CFM, posterior SB non-inflation, and TM, (2) provides quantitative measurements for CFM and TM, and (3) defines impacts on higher biological levels including food ingestion, swimming, and survival. Results show that all-trans retinoic acid (ATRA) induces strong teratogenic effects with sensitivity windows between 4 and 48 h post fertilization (hpf) for CFM, TM, and posterior SB non-inflation. TM is the most sensitive indicator, with EC50 of 0.2 - 0.26 mu g/L across exposure windows 4-48, 4-72, 4-96, and 4-120 hpf. Besides inducing known malformations, ATRA impaired posterior SB inflation with EC50 of 1 - 1.21 mu g/L across the same exposure windows. ATRA exposure (1 mu g/L) resulted in 50 % food ingestion inhibition at 7 days post fertilization (dpf) and 10 % survival at 14 dpf. This study provides a regulatory-relevant framework linking developmental effects to population outcomes, highlighting ecological risks and needs for improved risk assessments.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30108 - Toxicology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Aquatic toxicology

ISSN

0166-445X

e-ISSN

—

Volume of the periodical

277

Issue of the periodical within the volume

December 2024

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

12

Pages from-to

1-12

UT code for WoS article

001359380000001

EID of the result in the Scopus database

2-s2.0-85208913133