Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project

Albert Braeuning; Patrick Balaguer; William Bourguet; Jordi Carreras-Puigvert; Katreece Feiertag; Jorke H Kamstra; Dries Knapen; Dajana Lichtenstein; Philip Marx-Stoelting; Jonne Rietdijk; Kristin Schubert; Ola Spjuth; Evelyn Stinckens; Kathrin Thedieck; Rik van den Boom; Lucia Vergauwen; Martin von Bergen; Neele Wewer; Daniel Zalko

doi:10.3389/ftox.2023.1212509

Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project

Albert Braeuning^*, Patrick Balaguer, William Bourguet, Jordi Carreras-Puigvert, Katreece Feiertag, Jorke H Kamstra, Dries Knapen, Dajana Lichtenstein, Philip Marx-Stoelting, Jonne Rietdijk, Kristin Schubert, Ola Spjuth, Evelyn Stinckens, Kathrin Thedieck, Rik van den Boom, Lucia Vergauwen, Martin von Bergen, Neele Wewer, Daniel Zalko

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. More recently, disruption of energy metabolism and related signaling pathways by exogenous substances, so-called metabolism-disrupting chemicals (MDCs) have come into focus. While general effects such as body and organ weight changes are routinely monitored in animal studies, there is a clear lack of mechanistic test systems to determine and characterize the metabolism-disrupting potential of chemicals. In order to contribute to filling this gap, one of the project within EU-funded Partnership for the Assessment of Risks of Chemicals (PARC) aims at developing novel in vitro methods for the detection of endocrine metabolic disruptors. Efforts will comprise projects related to specific signaling pathways, for example, involving mTOR or xenobiotic-sensing nuclear receptors, studies on hepatocytes, adipocytes and pancreatic beta cells covering metabolic and morphological endpoints, as well as metabolism-related zebrafish-based tests as an alternative to classic rodent bioassays. This paper provides an overview of the approaches and methods of these PARC projects and how this will contribute to the improvement of the toxicological toolbox to identify substances with endocrine disrupting properties and to decipher their mechanisms of action.

Original language	English
Article number	1212509
Number of pages	7
Journal	Frontiers in Toxicology
Volume	5
DOIs	https://doi.org/10.3389/ftox.2023.1212509
Publication status	Published - 29 Jun 2023

Bibliographical note

Funding Information:
This work was supported by Horizon Europe, the European Union’s 2021–2027 framework program for the funding of research and innovation under der grant agreement No. 101057014 (project PARC). Additional co-funding of the University of Antwerp Research Fund through a GOA project (FFB180348/36572) is acknowledged.

Publisher Copyright:
Copyright © 2023 Braeuning, Balaguer, Bourguet, Carreras-Puigvert, Feiertag, Kamstra, Knapen, Lichtenstein, Marx-Stoelting, Rietdijk, Schubert, Spjuth, Stinckens, Thedieck, van den Boom, Vergauwen, von Bergen, Wewer and Zalko.

Keywords

adipocytes
endocrine metabolic disruption
energy metabolism
liver
nuclear receptors
obesogens

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10.3389/ftox.2023.1212509Licence: CC BY

ftox-05-1212509Final published version, 852 KBLicence: CC BY

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Braeuning, A., Balaguer, P., Bourguet, W., Carreras-Puigvert, J., Feiertag, K., Kamstra, J. H., Knapen, D., Lichtenstein, D., Marx-Stoelting, P., Rietdijk, J., Schubert, K., Spjuth, O., Stinckens, E., Thedieck, K., van den Boom, R., Vergauwen, L., von Bergen, M., Wewer, N., & Zalko, D. (2023). Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project. Frontiers in Toxicology, 5, Article 1212509. https://doi.org/10.3389/ftox.2023.1212509

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abstract = "In past times, the analysis of endocrine disrupting properties of chemicals has mainly been focused on (anti-)estrogenic or (anti-)androgenic properties, as well as on aspects of steroidogenesis and the modulation of thyroid signaling. More recently, disruption of energy metabolism and related signaling pathways by exogenous substances, so-called metabolism-disrupting chemicals (MDCs) have come into focus. While general effects such as body and organ weight changes are routinely monitored in animal studies, there is a clear lack of mechanistic test systems to determine and characterize the metabolism-disrupting potential of chemicals. In order to contribute to filling this gap, one of the project within EU-funded Partnership for the Assessment of Risks of Chemicals (PARC) aims at developing novel in vitro methods for the detection of endocrine metabolic disruptors. Efforts will comprise projects related to specific signaling pathways, for example, involving mTOR or xenobiotic-sensing nuclear receptors, studies on hepatocytes, adipocytes and pancreatic beta cells covering metabolic and morphological endpoints, as well as metabolism-related zebrafish-based tests as an alternative to classic rodent bioassays. This paper provides an overview of the approaches and methods of these PARC projects and how this will contribute to the improvement of the toxicological toolbox to identify substances with endocrine disrupting properties and to decipher their mechanisms of action. ",

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author = "Albert Braeuning and Patrick Balaguer and William Bourguet and Jordi Carreras-Puigvert and Katreece Feiertag and Kamstra, {Jorke H} and Dries Knapen and Dajana Lichtenstein and Philip Marx-Stoelting and Jonne Rietdijk and Kristin Schubert and Ola Spjuth and Evelyn Stinckens and Kathrin Thedieck and {van den Boom}, Rik and Lucia Vergauwen and {von Bergen}, Martin and Neele Wewer and Daniel Zalko",

note = "Funding Information: This work was supported by Horizon Europe, the European Union{\textquoteright}s 2021–2027 framework program for the funding of research and innovation under der grant agreement No. 101057014 (project PARC). Additional co-funding of the University of Antwerp Research Fund through a GOA project (FFB180348/36572) is acknowledged. Publisher Copyright: Copyright {\textcopyright} 2023 Braeuning, Balaguer, Bourguet, Carreras-Puigvert, Feiertag, Kamstra, Knapen, Lichtenstein, Marx-Stoelting, Rietdijk, Schubert, Spjuth, Stinckens, Thedieck, van den Boom, Vergauwen, von Bergen, Wewer and Zalko.",

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Braeuning, A, Balaguer, P, Bourguet, W, Carreras-Puigvert, J, Feiertag, K, Kamstra, JH, Knapen, D, Lichtenstein, D, Marx-Stoelting, P, Rietdijk, J, Schubert, K, Spjuth, O, Stinckens, E, Thedieck, K, van den Boom, R, Vergauwen, L, von Bergen, M, Wewer, N & Zalko, D 2023, 'Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project', Frontiers in Toxicology, vol. 5, 1212509. https://doi.org/10.3389/ftox.2023.1212509

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AU - Balaguer, Patrick

AU - Bourguet, William

AU - Carreras-Puigvert, Jordi

AU - Feiertag, Katreece

AU - Kamstra, Jorke H

AU - Knapen, Dries

AU - Lichtenstein, Dajana

AU - Marx-Stoelting, Philip

AU - Rietdijk, Jonne

AU - Schubert, Kristin

AU - Spjuth, Ola

AU - Stinckens, Evelyn

AU - Thedieck, Kathrin

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AU - Vergauwen, Lucia

AU - von Bergen, Martin

AU - Wewer, Neele

AU - Zalko, Daniel

N1 - Funding Information: This work was supported by Horizon Europe, the European Union’s 2021–2027 framework program for the funding of research and innovation under der grant agreement No. 101057014 (project PARC). Additional co-funding of the University of Antwerp Research Fund through a GOA project (FFB180348/36572) is acknowledged. Publisher Copyright: Copyright © 2023 Braeuning, Balaguer, Bourguet, Carreras-Puigvert, Feiertag, Kamstra, Knapen, Lichtenstein, Marx-Stoelting, Rietdijk, Schubert, Spjuth, Stinckens, Thedieck, van den Boom, Vergauwen, von Bergen, Wewer and Zalko.

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KW - energy metabolism

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KW - nuclear receptors

KW - obesogens

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Development of new approach methods for the identification and characterization of endocrine metabolic disruptors-a PARC project

Abstract

Bibliographical note

Keywords

Access to Document

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Corrigendum: Development of new approach methods for the identification and characterization of endocrine metabolic disruptors—a PARC project(Front. Toxicol., (2023), 5, (1212509), 10.3389/ftox.2023.1212509)

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