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Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives

Drug-induced testicular injury (DITI) is one of the often-observed and challenging safety issues seen during drug development. Semen analysis and circulating hormones currently utilized have significant gaps in their ability to detect testicular damage accurately. In addition, no biomarkers enable a...

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Autores principales: Zhang, Jiangwei, Campion, Sarah, Catlin, Natasha, Reagan, William J., Palyada, Kiran, Ramaiah, Shashi K., Ramanathan, Ragu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933818/
https://www.ncbi.nlm.nih.gov/pubmed/36795116
http://dx.doi.org/10.1007/s00204-023-03460-0
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author Zhang, Jiangwei
Campion, Sarah
Catlin, Natasha
Reagan, William J.
Palyada, Kiran
Ramaiah, Shashi K.
Ramanathan, Ragu
author_facet Zhang, Jiangwei
Campion, Sarah
Catlin, Natasha
Reagan, William J.
Palyada, Kiran
Ramaiah, Shashi K.
Ramanathan, Ragu
author_sort Zhang, Jiangwei
collection PubMed
description Drug-induced testicular injury (DITI) is one of the often-observed and challenging safety issues seen during drug development. Semen analysis and circulating hormones currently utilized have significant gaps in their ability to detect testicular damage accurately. In addition, no biomarkers enable a mechanistic understanding of the damage to the different regions of the testis, such as seminiferous tubules, Sertoli, and Leydig cells. MicroRNAs (miRNAs) are a class of non-coding RNAs that modulate gene expression post-transcriptionally and have been indicated to regulate a wide range of biological pathways. Circulating miRNAs can be measured in the body fluids due to tissue-specific cell injury/damage or toxicant exposure. Therefore, these circulating miRNAs have become attractive and promising non-invasive biomarkers for assessing drug-induced testicular injury, with several reports on their use as safety biomarkers for monitoring testicular damage in preclinical species. Leveraging emerging tools such as ‘organs-on-chips’ that can emulate the human organ’s physiological environment and function is starting to enable biomarker discovery, validation, and clinical translation for regulatory qualification and implementation in drug development.
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spelling pubmed-99338182023-02-17 Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives Zhang, Jiangwei Campion, Sarah Catlin, Natasha Reagan, William J. Palyada, Kiran Ramaiah, Shashi K. Ramanathan, Ragu Arch Toxicol Review Article Drug-induced testicular injury (DITI) is one of the often-observed and challenging safety issues seen during drug development. Semen analysis and circulating hormones currently utilized have significant gaps in their ability to detect testicular damage accurately. In addition, no biomarkers enable a mechanistic understanding of the damage to the different regions of the testis, such as seminiferous tubules, Sertoli, and Leydig cells. MicroRNAs (miRNAs) are a class of non-coding RNAs that modulate gene expression post-transcriptionally and have been indicated to regulate a wide range of biological pathways. Circulating miRNAs can be measured in the body fluids due to tissue-specific cell injury/damage or toxicant exposure. Therefore, these circulating miRNAs have become attractive and promising non-invasive biomarkers for assessing drug-induced testicular injury, with several reports on their use as safety biomarkers for monitoring testicular damage in preclinical species. Leveraging emerging tools such as ‘organs-on-chips’ that can emulate the human organ’s physiological environment and function is starting to enable biomarker discovery, validation, and clinical translation for regulatory qualification and implementation in drug development. Springer Berlin Heidelberg 2023-02-16 2023 /pmc/articles/PMC9933818/ /pubmed/36795116 http://dx.doi.org/10.1007/s00204-023-03460-0 Text en © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Review Article
Zhang, Jiangwei
Campion, Sarah
Catlin, Natasha
Reagan, William J.
Palyada, Kiran
Ramaiah, Shashi K.
Ramanathan, Ragu
Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives
title Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives
title_full Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives
title_fullStr Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives
title_full_unstemmed Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives
title_short Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives
title_sort circulating micrornas as promising testicular translatable safety biomarkers: current state and future perspectives
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933818/
https://www.ncbi.nlm.nih.gov/pubmed/36795116
http://dx.doi.org/10.1007/s00204-023-03460-0
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