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Cited by 30Sperm and Testicular FunctionMicroRNA in disease regulationAnimal Genetics and Reproduction

Dysregulated microRNA Clusters in Response to Retinoic Acid and CYP26B1 Inhibitor Induced Testicular Function in Dogs

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Kasimanickam, Vanmathy R., Kasimanickam, Ramanathan K., Dernell, William S.·2014·PLoS ONE
DOI 10.1371/journal.pone.0099433PMC PMC4049822
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Abstract

Spermatogenesis is a multistep synchronized process. Diploid spermatogonia differentiate into haploid spermatozoa following mitosis, meiosis and spermiogenesis. Division and differentiation of male germ cells is achieved through the sequential expression of several genes. Numerous mRNAs in the differentiating germ cells undergo post-transcriptional and translational regulation. MiRNAs are powerful negative regulators of mRNA transcription, stability, and translation and recognize their mRNA targets through base-pairing. Retinoic acid (RA) signaling is essential for spermatogenesis and testicular function. Testicular RA level is critical for RA signal transduction. This study investigated the miRNAs modulation in an RA- induced testicular environment following the administration of all-trans RA (2 µM) and CYP26B1- inhibitor (1 µM) compared to control. Eighty four canine mature miRNAs were analyzed and their expression signatures were distinguished using real-time PCR based array technology. Of the miRNAs analyzed, miRNA families such as miR-200 (cfa-miR-200a, cfa-miR-200b and cfa-miR-200c), Mirlet-7 (cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa-let-7g and cfa-let-7f), miR-125 (cfa-miR-125a and cfa-miR-125b), miR-146 (cfa-miR-146a and cfa-miR-146b), miR-34 (cfa-miR-34a, cfa-miR-34b and cfa-miR-34c), miR-23 (cfa-miR-23a and cfa-miR-23b), cfa-miR-184, cfa-miR-214 and cfa-miR-141 were significantly up-regulated with testicular RA intervention via administration of CYP26B1 inhibitor and all-trans-RA and species of miRNA such as cfa-miR-19a, cfa-miR-29b, cfa-miR-29c, cfa-miR-101 and cfa-miR-137 were significantly down-regulated. This study explored information regarding chromosome distribution, human orthologous sequences and the interaction of target genes of miRNA families significantly distinguished in this study using prediction algorithms. This study importantly identified dysregulated miRNA species resulting from RA-induced spermatogenesis. The present contribution serves as a useful resource for further elucidation of the regulatory role of individual miRNA in RA synchronized canine spermatogenesis.

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  • In dogs, the miRNA expression profile of dysfunctional testis response induced by RA and Cyp26b1 inhibitors found that the miR-23 family was significantly downregulated.

    “The miRNA expression profile of dysfunctional testis response induced by RA and Cyp26b1 inhibitors in dogs found that the miR-23 family was significantly downregulated [128].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [128]

    The Results and Discussion report that the miR-23 family (cfa-miR-23a and cfa-miR-23b) was significantly up-regulated after RA or CYP26B1 inhibitor treatment in canine testis, not downregulated. The Figure 5 caption also lists cfa-miR-23 among the up-regulated clusters. (LLM, conf=0.95)

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  • miR-23 is involved in the mechanism of spermatogenesis and can regulate male reproductive function.

    “miR-23 is also involved in the mechanism of spermatogenesis and can regulate male reproductive function.”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [128]

    The Results and Discussion (page unavailable) report that canine miR-23a and miR-23b were significantly up-regulated after retinoic-acid intervention in testes, supporting an association with a spermatogenesis-related pathway. The paper does not establish that miR-23 regulates spermatogenesis or male reproductive function; it presents the regulatory roles of individual miRNAs as needing further elucidation. (LLM, conf=0.86)

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Authors
Kasimanickam, V. R., Kasimanickam, R. K., & Dernell, W. S.
Affiliations
Washington State University (US)
Corresponding author
Kasimanickam, Vanmathy R.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-06-09
Volume
9
Issue
6
Pages
e99433
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0099433
PMC
PMC4049822
OpenAlex
W1977024213
Cited by
30
References
47
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 3
FWCI
5.26
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
Washington State University
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
Keywords
microRNA expression, retinoic acid signaling, all-trans retinoic acid, spermatogenesis, testicular function, canine, miR-200 family, miR-34 family, miR-141
MeSH terms
Retinoic Acid 4-Hydroxylase, Animals, Cytochrome P-450 Enzyme System, Dogs, Gene Expression Regulation, Multigene Family, Male, Testis, Tretinoin, Triazoles, Cluster Analysis, Gene Expression Profiling, MicroRNAs, Benzothiazoles, Gene Regulatory Networks, Transcriptome, Cytochrome P-450 Enzyme Inhibitors

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