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


Journal

Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615

Informations de publication

Date de publication:
04 2023
Historique:
received: 12 12 2022
accepted: 07 02 2023
pubmed: 17 2 2023
medline: 22 3 2023
entrez: 16 2 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36795116
doi: 10.1007/s00204-023-03460-0
pii: 10.1007/s00204-023-03460-0
pmc: PMC9933818
doi:

Substances chimiques

Circulating MicroRNA 0
MicroRNAs 0
Biomarkers 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

947-961

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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Auteurs

Jiangwei Zhang (J)

Drug Safety Research & Development, Pfizer Worldwide Research, Development & Medical, 10777 Science Center Dr, San Diego, CA, USA.

Sarah Campion (S)

Drug Safety Research & Development, Pfizer Worldwide Research, Development & Medical, 445 Eastern Point Rd., Groton, CT, USA.

Natasha Catlin (N)

Drug Safety Research & Development, Pfizer Worldwide Research, Development & Medical, 445 Eastern Point Rd., Groton, CT, USA.

William J Reagan (WJ)

Drug Safety Research & Development, Pfizer Worldwide Research, Development & Medical, 445 Eastern Point Rd., Groton, CT, USA.

Kiran Palyada (K)

Drug Safety Research & Development, Pfizer Worldwide Research, Development & Medical, 10777 Science Center Dr, San Diego, CA, USA.

Shashi K Ramaiah (SK)

Drug Safety Research & Development, Pfizer Worldwide Research, Development & Medical, 1 Portland St., Cambridge, MA, 02139, USA.

Ragu Ramanathan (R)

Drug Safety Research & Development, Pfizer Worldwide Research, Development & Medical, 445 Eastern Point Rd., Groton, CT, USA. ragu.ramanathan@pfizer.com.

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