Comparative analysis of transcriptomic points-of-departure
(tPODs) and apical responses in embryo-larval fathead minnows
exposed to fluoxetine

J 2022

Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine

ALCARAZ, Alper James G., Shaina BARANIUK, Kamil MIKULÁŠEK, Bradley PARK, Taylor LANE et. al.

Basic information

Original name

Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine

Authors

ALCARAZ, Alper James G. (124 Canada), Shaina BARANIUK (124 Canada), Kamil MIKULÁŠEK (203 Czech Republic, belonging to the institution), Bradley PARK (124 Canada), Taylor LANE (124 Canada), Connor BURBRIDGE (124 Canada), Jessica EWALD (124 Canada), David POTĚŠIL (203 Czech Republic, belonging to the institution), Jianguo XIA (124 Canada), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution), David SCHNEIDER (124 Canada), Doug CRUMP (124 Canada), Niladri BASU (124 Canada), Natacha HOGAN (124 Canada), Markus BRINKMANN (124 Canada) and Markus HECKER (124 Canada)

Edition

ENVIRONMENTAL POLLUTION, ENGLAND, ELSEVIER SCI LTD, 2022, 0269-7491

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10511 Environmental sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

fulltext

Impact factor

Impact factor: 8.900

RIV identification code

RIV/00216224:14740/22:00125954

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.envpol.2021.118667

UT WoS

000760279500002

Keywords in English

Benchmark dose (BMD); Selective serotonin reuptake inhibitor (SSRI); Hazard assessment; Live-animal alternatives; New approach methodology (NAM)

Abstract

V originále

Current approaches in chemical hazard assessment face significant challenges because they rely on live animal testing, which is time-consuming, expensive, and ethically questionable. These concerns serve as an impetus to develop new approach methodologies (NAMs) that do not rely on live animal tests. This study explored a molecular benchmark dose (BMD) approach using a 7-day embryo-larval fathead minnow (FHM) assay to derive transcriptomic points-of-departure (tPODs) to predict apical BMDs of fluoxetine (FLX), a highly prescribed and potent selective serotonin reuptake inhibitor frequently detected in surface waters. Fertilized FHM embryos were exposed to graded concentrations of FLX (confirmed at < LOD, 0.19, 0.74, 3.38, 10.2, 47.5 mu g/L) for 32 days. Subsets of fish were subjected to omics and locomotor analyses at 7 days post-fertilization (dpf) and to histological and biometric measurements at 32 dpf. Enrichment analyses of transcriptomics and proteomics data revealed significant perturbations in gene sets associated with serotonergic and axonal functions. BMD analysis resulted in tPOD values of 0.56 mu g/L (median of the 20 most sensitive gene-level BMDs), 5.0 mu g/L (tenth percentile of all gene-level BMDs), 7.51 mu g/L (mode of the first peak of all gene-level BMDs), and 5.66 mu g/L (pathway-level BMD). These tPODs were protective of locomotor and reduced body weight effects (LOEC of 10.2 mu g/L) observed in this study and were reflective of chronic apical BMDs of FLX reported in the literature. Furthermore, the distribution of gene-level BMDs followed a bimodal pattern, revealing disruption of sensitive neurotoxic pathways at low concentrations and metabolic pathway perturbations at higher concentrations. This is one of the first studies to derive protective tPODs for FLX using a short-term embryo assay at a life stage not considered to be a live animal under current legislations.

Links

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

ALCARAZ, Alper James G., Shaina BARANIUK, Kamil MIKULÁŠEK, Bradley PARK, Taylor LANE, Connor BURBRIDGE, Jessica EWALD, David POTĚŠIL, Jianguo XIA, Zbyněk ZDRÁHAL, David SCHNEIDER, Doug CRUMP, Niladri BASU, Natacha HOGAN, Markus BRINKMANN and Markus HECKER. Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine. ENVIRONMENTAL POLLUTION. ENGLAND: ELSEVIER SCI LTD, 2022, vol. 295, FEB, p. "118667", 12 pp. ISSN 0269-7491. Available from: https://dx.doi.org/10.1016/j.envpol.2021.118667.

@article{1858780,
   author = {Alcaraz, Alper James G. and Baraniuk, Shaina and Mikulášek, Kamil and Park, Bradley and Lane, Taylor and Burbridge, Connor and Ewald, Jessica and Potěšil, David and Xia, Jianguo and Zdráhal, Zbyněk and Schneider, David and Crump, Doug and Basu, Niladri and Hogan, Natacha and Brinkmann, Markus and Hecker, Markus},
   article_location = {ENGLAND},
   article_number = {FEB},
   doi = {http://dx.doi.org/10.1016/j.envpol.2021.118667},
   keywords = {Benchmark dose (BMD); Selective serotonin reuptake inhibitor (SSRI); Hazard assessment; Live-animal alternatives; New approach methodology (NAM)},
   language = {eng},
   issn = {0269-7491},
   journal = {ENVIRONMENTAL POLLUTION},
   title = {Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine},
   url = {http://www.sciencedirect.com/science/article/pii/S0269749121022491},
   volume = {295},
   year = {2022}
}

TY  - JOUR
ID  - 1858780
AU  - Alcaraz, Alper James G. - Baraniuk, Shaina - Mikulášek, Kamil - Park, Bradley - Lane, Taylor - Burbridge, Connor - Ewald, Jessica - Potěšil, David - Xia, Jianguo - Zdráhal, Zbyněk - Schneider, David - Crump, Doug - Basu, Niladri - Hogan, Natacha - Brinkmann, Markus - Hecker, Markus
PY  - 2022
TI  - Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine
JF  - ENVIRONMENTAL POLLUTION
VL  - 295
IS  - FEB
SP  - "118667"
EP  - "118667"
PB  - ELSEVIER SCI LTD
SN  - 02697491
KW  - Benchmark dose (BMD)
KW  - Selective serotonin reuptake inhibitor (SSRI)
KW  - Hazard assessment
KW  - Live-animal alternatives
KW  - New approach methodology (NAM)
UR  - http://www.sciencedirect.com/science/article/pii/S0269749121022491
N2  - Current approaches in chemical hazard assessment face significant challenges because they rely on live animal testing, which is time-consuming, expensive, and ethically questionable. These concerns serve as an impetus to develop new approach methodologies (NAMs) that do not rely on live animal tests. This study explored a molecular benchmark dose (BMD) approach using a 7-day embryo-larval fathead minnow (FHM) assay to derive transcriptomic points-of-departure (tPODs) to predict apical BMDs of fluoxetine (FLX), a highly prescribed and potent selective serotonin reuptake inhibitor frequently detected in surface waters. Fertilized FHM embryos were exposed to graded concentrations of FLX (confirmed at < LOD, 0.19, 0.74, 3.38, 10.2, 47.5 mu g/L) for 32 days. Subsets of fish were subjected to omics and locomotor analyses at 7 days post-fertilization (dpf) and to histological and biometric measurements at 32 dpf. Enrichment analyses of transcriptomics and proteomics data revealed significant perturbations in gene sets associated with serotonergic and axonal functions. BMD analysis resulted in tPOD values of 0.56 mu g/L (median of the 20 most sensitive gene-level BMDs), 5.0 mu g/L (tenth percentile of all gene-level BMDs), 7.51 mu g/L (mode of the first peak of all gene-level BMDs), and 5.66 mu g/L (pathway-level BMD). These tPODs were protective of locomotor and reduced body weight effects (LOEC of 10.2 mu g/L) observed in this study and were reflective of chronic apical BMDs of FLX reported in the literature. Furthermore, the distribution of gene-level BMDs followed a bimodal pattern, revealing disruption of sensitive neurotoxic pathways at low concentrations and metabolic pathway perturbations at higher concentrations. This is one of the first studies to derive protective tPODs for FLX using a short-term embryo assay at a life stage not considered to be a live animal under current legislations.
ER  -

ALCARAZ, Alper James G., Shaina BARANIUK, Kamil MIKULÁŠEK, Bradley PARK, Taylor LANE, Connor BURBRIDGE, Jessica EWALD, David POTĚŠIL, Jianguo XIA, Zbyněk ZDRÁHAL, David SCHNEIDER, Doug CRUMP, Niladri BASU, Natacha HOGAN, Markus BRINKMANN and Markus HECKER. Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine. \textit{ENVIRONMENTAL POLLUTION}. ENGLAND: ELSEVIER SCI LTD, 2022, vol.~295, FEB, p.~''118667'', 12 pp. ISSN~0269-7491. Available from: https://dx.doi.org/10.1016/j.envpol.2021.118667.

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