Kinetics of the chromosome 14 microRNA cluster ortholog and its potential role during placental development in the pregnant mare.
Abstract: The human chromosome 14 microRNA cluster (C14MC) is a conserved microRNA (miRNA) cluster across eutherian mammals, reported to play an important role in placental development. However, the expression kinetics and function of this cluster in the mammalian placenta are poorly understood. Here, we evaluated the expression kinetics of the equine C24MC, ortholog to the human C14MC, in the chorioallantoic membrane during the course of gestation. Results: We demonstrated that C24MC-associated miRNAs presented a higher expression level during early stages of pregnancy, followed by a decline later in gestation. Evaluation of one member of C24MC (miR-409-3p) by in situ hybridization demonstrated that its cellular localization predominantly involved the chorion and allantoic epithelium and vascular endothelium. Additionally, expression of predicted target transcripts for C24MC-associated miRNAs was evaluated by RNA sequencing. Expression analysis of a subset of predicted mRNA targets showed a negative correlation with C24MC-associated miRNAs expression levels during gestation, suggesting the reciprocal control of these target transcripts by this miRNA cluster. Predicted functional analysis of these target mRNAs indicated enrichment of biological pathways related to embryonic development, endothelial cell migration and angiogenesis. Expression patterns of selected target mRNAs involved in angiogenesis were confirmed by RT-qPCR. Conclusions: This is the first report evaluating C24MC kinetics during pregnancy. The findings presented herein suggest that the C24MC may modulate angiogenic transcriptional profiles during placental development in the horse.
Publication Date: 2018-12-20 PubMed ID: 30572819PubMed Central: PMC6302407DOI: 10.1186/s12864-018-5341-2Google Scholar: Lookup
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Summary
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This study investigates the behavior of the equine counterpart of a human microRNA cluster (sequences of RNA that regulate gene expression) known as C14MC during horse pregnancy. The researchers found that this cluster, named C24MC in horses, had higher expression in the early stages of pregnancy and then declined. They also discovered that C24MC might regulate certain gene activities related to placental development.
Research Methodology
- The researchers evaluated the expression of the equine C24MC, very similar to the human C14MC, in the chorioallantoic membrane, an area of the placenta, during the entirety of gestation.
- The researchers used a method called ‘in situ hybridization’ to find the cellular locations of one component of C24MC (miR-409-3p), i.e., where within the cells this specific microRNA was located.
- The team also determined the expression of transcripts (a copy of gene’s DNA sequence turned into RNA) that were predicted to be the target of the microRNAs in the C24MC cluster using RNA sequencing, a technology used to see how many RNA molecules are present from a specific gene.
Study Findings
- The study revealed that C24MC-associated microRNAs had higher expression levels at the initial stages of pregnancy, and then their expression declined later in gestation.
- Another significant finding was that the cellular localization of miR-409-3p was mainly in the chorion and allantoic epithelium and vascular endothelium, parts of the placenta crucial for nutrient exchange between mother and fetus.
- The analysis on expression levels of predicted mRNA targets correlated inversely with C24MC-associated miRNAs expression levels during gestation, which indicates that this miRNA cluster can potentially regulate these target transcripts.
Implications
- The predicted targets of the C24MC cluster were linked with biological pathways associated with embryonic development, endothelial cell migration, and angiogenesis, which is the formation of new blood vessels – all critical processes in placental development during pregnancy.
- The study was able to confirm, using RT-qPCR, a method to determine the number of specific RNA transcripts, the expression patterns of selected target mRNAs involved in angiogenesis.
- This study’s findings suggest C24MC’s potential role in modulating angiogenic transcriptional profiles during placental development. Thus, it could play a crucial role in the course of pregnancy for horses – and potentially other mammals as C14MC is conserved across many other mammalian species. This could lead to broader implications for human health and medicine.
Cite This Article
APA
Dini P, Daels P, Loux SC, Esteller-Vico A, Carossino M, Scoggin KE, Ball BA.
(2018).
Kinetics of the chromosome 14 microRNA cluster ortholog and its potential role during placental development in the pregnant mare.
BMC Genomics, 19(1), 954.
https://doi.org/10.1186/s12864-018-5341-2 Publication
Researcher Affiliations
- Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
- Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
- Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA. b.a.ball@uky.edu.
MeSH Terms
- Animals
- Chorioallantoic Membrane / growth & development
- Chorioallantoic Membrane / metabolism
- Chromosomes, Human, Pair 14
- Female
- Gene Expression Profiling / veterinary
- Horses
- Humans
- Kinetics
- MicroRNAs / genetics
- Placentation
- Pregnancy
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Transcriptome
Conflict of Interest Statement
ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All animal procedures were prospectively approved by and completed in accordance with the Institutional Animal Care and Use Committee of the University of Kentucky (Protocols # 2014-1341 and 2014-1215). CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Citations
This article has been cited 11 times.- Orellana-Guerrero D, Uribe-Salazar JM, El-Sheikh Ali H, Scoggin KE, Ball B, Daels P, Finno CJ, Dini P. Dynamics of the Equine Placental DNA Methylome and Transcriptome from Mid- to Late Gestation.. Int J Mol Sci 2023 Apr 11;24(8).
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- Dini P, Kalbfleisch T, Uribe-Salazar JM, Carossino M, Ali HE, Loux SC, Esteller-Vico A, Norris JK, Anand L, Scoggin KE, Rodriguez Lopez CM, Breen J, Bailey E, Daels P, Ball BA. Parental bias in expression and interaction of genes in the equine placenta.. Proc Natl Acad Sci U S A 2021 Apr 20;118(16).
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