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Home / Equine Research Bank / PLoS One / Evaluation of circulating miRNAs during late pregnancy in th...
PloS one2017; 12(4); e0175045; doi: 10.1371/journal.pone.0175045

Evaluation of circulating miRNAs during late pregnancy in the mare.

Abstract: MicroRNAs (miRNAs) are small, non-coding RNAs which are produced throughout the body. Individual tissues tend to have a specific expression profile and excrete many of these miRNAs into circulation. These circulating miRNAs may be diagnostically valuable biomarkers for assessing the presence of disease while minimizing invasive testing. In women, numerous circulating miRNAs have been identified which change significantly during pregnancy-related complications (e.g. chorioamnionitis, eclampsia, recurrent pregnancy loss); however, no prior work has been done in this area in the horse. To identify pregnancy-specific miRNAs, we collected serial whole blood samples in pregnant mares at 8, 9, 10 m of gestation and post-partum, as well as from non-pregnant (diestrous) mares. In total, we evaluated a panel of 178 miRNAs using qPCR, eventually identifying five miRNAs of interest. One miRNA (miR-374b) was differentially regulated through late gestation and four miRNAs (miR-454, miR-133b, miR-486-5p and miR-204b) were differentially regulated between the pregnant and non-pregnant samples. We were able to identify putative targets for the differentially regulated miRNAs using two separate target prediction programs, miRDB and Ingenuity Pathway Analysis. The targets for the miRNAs differentially regulated during pregnancy were predicted to be involved in signaling pathways such as the STAT3 pathway and PI3/AKT signaling pathway, as well as more endocrine-based pathways, including the GnRH, prolactin and insulin signaling pathways. In summary, this study provides novel information about the changes occurring in circulating miRNAs during normal pregnancy, as well as attempting to predict the biological effects induced by these miRNAs.
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Publication Date: 2017-04-07 PubMed ID: 28388652PubMed Central: PMC5384662DOI: 10.1371/journal.pone.0175045Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper investigates the changes in circulating microRNAs (miRNAs) in horses during late pregnancy, identifying five miRNAs of interest. These findings contribute to the understanding of the biological effects these miRNAs may induce during this period.

Background

  • The paper focuses on miRNAs, non-coding RNAs found throughout the body. Individual tissues express these miRNAs in specific profiles and release many into circulation, potentially offering useful biomarkers for diagnosing disease with minimal invasive testing.
  • Prior studies have identified numerous circulating miRNAs showing significant changes during pregnancy complications in women, such as chorioamnionitis, eclampsia, and recurrent pregnancy loss.
  • However, studies in the realm of equine pregnancy have been absent, which instigated the present research.

Methodology

  • The researchers collected whole blood samples from pregnant mares multiple times during different months of gestation and post-partum, as well as from non-pregnant mares.
  • Out of a panel of 178 miRNAs, they used quantitative PCR to evaluate each miRNA for any significant changes in expression during pregnancy.

Findings

  • The study discovered five miRNAs of interest, out of which one (miR-374b) was differentially regulated during late gestation.
  • The other four miRNAs (miR-454, miR-133b, miR-486-5p, and miR-204b) displayed differential regulation between the pregnant and non-pregnant samples.
  • To understand the biological implications of these changes, the researchers used two separate target prediction programs (miRDB and Ingenuity Pathway Analysis) to identify potential targets for the differentially regulated miRNAs.

Implications

  • The potential targets for the differentially regulated miRNAs were predicted to participate in signaling pathways like the STAT3 pathway, the PI3/AKT signaling pathway, and endocrine-related pathways like the GnRH, prolactin, and insulin signaling pathways.
  • This data contributes valuable insights on the alterations happening in circulating miRNAs during normal pregnancy and attempts to highlight the possible biological effects prompted by these miRNAs.

Cite This Article

APA
Loux SC, Scoggin KE, Bruemmer JE, Canisso IF, Troedsson MH, Squires EL, Ball BA. (2017). Evaluation of circulating miRNAs during late pregnancy in the mare. PLoS One, 12(4), e0175045. https://doi.org/10.1371/journal.pone.0175045

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 12
Issue: 4
Pages: e0175045
PII: e0175045

Researcher Affiliations

Loux, Shavahn C
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Scoggin, Kirsten E
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Bruemmer, Jason E
  • Department of Animal Sciences, Colorado State University, Fort Collins, CO, United States of America.
Canisso, Igor F
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL, United States of America.
Troedsson, Mats H T
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Squires, Edward L
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Ball, Barry A
  • Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.

MeSH Terms

  • Animals
  • Female
  • Horses
  • MicroRNAs / blood
  • Pregnancy
  • Pregnancy, Animal / blood
  • Reverse Transcriptase Polymerase Chain Reaction

Conflict of Interest Statement

One of our funding sources was a commercial source: the Kentucky Thoroughbred Association/Kentucky Thoroughbred Breeders and Owners. Although this is a commercial association, there are no ties to them through employment, consultancy, patents, products in development or marketed products. This group is comprised of local horse owners and breeders who are interested in learning more about the biology of pregnancy in the hopes of eventually reducing the incidence of late-term abortions in their own stock. Funding from this source does not alter our adherence to PLOS ONE policies on sharing data and materials.

References

This article includes 44 references
  1. Wilczynska A, Bushell M. The complexity of miRNA-mediated repression.. Cell Death Differ 2015 Jan;22(1):22-33.
    doi: 10.1038/cdd.2014.112pmc: PMC4262769pubmed: 25190144google scholar: lookup
  2. Ghai V, Wang K. Recent progress toward the use of circulating microRNAs as clinical biomarkers.. Arch Toxicol 2016 Dec;90(12):2959-2978.
    pubmed: 27585665doi: 10.1007/s00204-016-1828-2google scholar: lookup
  3. Singh R, Ramasubramanian B, Kanji S, Chakraborty AR, Haque SJ, Chakravarti A. Circulating microRNAs in cancer: Hope or hype?. Cancer Lett 2016 Oct 10;381(1):113-21.
    doi: 10.1016/j.canlet.2016.07.002pubmed: 27471105google scholar: lookup
  4. Hromadnikova I, Kotlabova K, Hympanova L, Krofta L. Gestational hypertension, preeclampsia and intrauterine growth restriction induce dysregulation of cardiovascular and cerebrovascular disease associated microRNAs in maternal whole peripheral blood.. Thromb Res 2016 Jan;137:126-140.
    doi: 10.1016/j.thromres.2015.11.032pubmed: 26632513google scholar: lookup
  5. Gantier MP, McCoy CE, Rusinova I, Saulep D, Wang D, Xu D, Irving AT, Behlke MA, Hertzog PJ, Mackay F, Williams BR. Analysis of microRNA turnover in mammalian cells following Dicer1 ablation.. Nucleic Acids Res 2011 Jul;39(13):5692-703.
    doi: 10.1093/nar/gkr148pmc: PMC3141258pubmed: 21447562google scholar: lookup
  6. He Y, Lin J, Kong D, Huang M, Xu C, Kim TK, Etheridge A, Luo Y, Ding Y, Wang K. Current State of Circulating MicroRNAs as Cancer Biomarkers.. Clin Chem 2015 Sep;61(9):1138-55.
    doi: 10.1373/clinchem.2015.241190pubmed: 26319452google scholar: lookup
  7. Maegdefessel L. The emerging role of microRNAs in cardiovascular disease.. J Intern Med 2014 Dec;276(6):633-44.
    doi: 10.1111/joim.12298pubmed: 25160930google scholar: lookup
  8. Sethupathy P. The Promise and Challenge of Therapeutic MicroRNA Silencing in Diabetes and Metabolic Diseases.. Curr Diab Rep 2016 Jun;16(6):52.
    doi: 10.1007/s11892-016-0745-3pmc: PMC4844637pubmed: 27112956google scholar: lookup
  9. Seeliger C, Balmayor ER, van Griensven M. miRNAs Related to Skeletal Diseases.. Stem Cells Dev 2016 Sep 1;25(17):1261-81.
    doi: 10.1089/scd.2016.0133pubmed: 27418331google scholar: lookup
  10. Mouillet JF, Ouyang Y, Coyne CB, Sadovsky Y. MicroRNAs in placental health and disease.. Am J Obstet Gynecol 2015 Oct;213(4 Suppl):S163-72.
    doi: 10.1016/j.ajog.2015.05.057pmc: PMC4592520pubmed: 26428496google scholar: lookup
  11. Zhao Z, Moley KH, Gronowski AM. Diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases.. Clin Biochem 2013 Jul;46(10-11):953-60.
    doi: 10.1016/j.clinbiochem.2013.01.026pubmed: 23396163google scholar: lookup
  12. Cretoiu D, Xu J, Xiao J, Suciu N, Cretoiu SM. Circulating MicroRNAs as Potential Molecular Biomarkers in Pathophysiological Evolution of Pregnancy.. Dis Markers 2016;2016:3851054.
    doi: 10.1155/2016/3851054pmc: PMC4967453pubmed: 27493447google scholar: lookup
  13. Klohonatz KM, Cameron AD, Hergenreder JR, da Silveira JC, Belk AD, Veeramachaneni DN, Bouma GJ, Bruemmer JE. Circulating miRNAs as Potential Alternative Cell Signaling Associated with Maternal Recognition of Pregnancy in the Mare.. Biol Reprod 2016 Dec;95(6):124.
    pubmed: 27760749doi: 10.1095/biolreprod.116.142935google scholar: lookup
  14. Mestdagh P, Van Vlierberghe P, De Weer A, Muth D, Westermann F, Speleman F, Vandesompele J. A novel and universal method for microRNA RT-qPCR data normalization.. Genome Biol 2009;10(6):R64.
    doi: 10.1186/gb-2009-10-6-r64pmc: PMC2718498pubmed: 19531210google scholar: lookup
  15. Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations.. Nucleic Acids Res 2015 Jan;43(Database issue):D146-52.
    doi: 10.1093/nar/gkᄄpmc: PMC4383922pubmed: 25378301google scholar: lookup
  16. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B (Methodological) 1995;57(1):289–300.
  17. Backes C, Meese E, Keller A. Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects.. Mol Diagn Ther 2016 Dec;20(6):509-518.
    pubmed: 27378479doi: 10.1007/s40291-016-0221-4google scholar: lookup
  18. Unger L, Fouché N, Leeb T, Gerber V, Pacholewska A. Optimized methods for extracting circulating small RNAs from long-term stored equine samples.. Acta Vet Scand 2016 Jun 29;58(1):44.
    doi: 10.1186/s13028-016-0224-5pmc: PMC4928274pubmed: 27356979google scholar: lookup
  19. Doss JF, Corcoran DL, Jima DD, Telen MJ, Dave SS, Chi JT. A comprehensive joint analysis of the long and short RNA transcriptomes of human erythrocytes.. BMC Genomics 2015 Nov 16;16:952.
    doi: 10.1186/s12864-015-2156-2pmc: PMC4647483pubmed: 26573221google scholar: lookup
  20. Brogaard L, Heegaard PM, Larsen LE, Mortensen S, Schlegel M, Dürrwald R, Skovgaard K. Late regulation of immune genes and microRNAs in circulating leukocytes in a pig model of influenza A (H1N2) infection.. Sci Rep 2016 Feb 19;6:21812.
    doi: 10.1038/srep21812pmc: PMC4759598pubmed: 26893019google scholar: lookup
  21. Pontes TB, Moreira-Nunes Cde F, Maués JH, Lamarão LM, de Lemos JA, Montenegro RC, Burbano RM. The miRNA Profile of Platelets Stored in a Blood Bank and Its Relation to Cellular Damage from Storage.. PLoS One 2015;10(6):e0129399.
    doi: 10.1371/journal.pone.0129399pmc: PMC4486185pubmed: 26121269google scholar: lookup
  22. Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW, Lo YM. Detection and characterization of placental microRNAs in maternal plasma.. Clin Chem 2008 Mar;54(3):482-90.
    doi: 10.1373/clinchem.2007.097972pubmed: 18218722google scholar: lookup
  23. Ladomery MR, Maddocks DG, Wilson ID. MicroRNAs: their discovery, biogenesis, function and potential use as biomarkers in non-invasive prenatal diagnostics.. Int J Mol Epidemiol Genet 2011 Aug 30;2(3):253-60.
    pmc: PMC3166153pubmed: 21915364
  24. Miura K, Miura S, Yamasaki K, Higashijima A, Kinoshita A, Yoshiura K, Masuzaki H. Identification of pregnancy-associated microRNAs in maternal plasma.. Clin Chem 2010 Nov;56(11):1767-71.
    doi: 10.1373/clinchem.2010.147660pubmed: 20729298google scholar: lookup
  25. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N, Bentwich Z, Hod M, Goren Y, Chajut A. Serum microRNAs are promising novel biomarkers.. PLoS One 2008 Sep 5;3(9):e3148.
    doi: 10.1371/journal.pone.0003148pmc: PMC2519789pubmed: 18773077google scholar: lookup
  26. Choi SY, Yun J, Lee OJ, Han HS, Yeo MK, Lee MA, Suh KS. MicroRNA expression profiles in placenta with severe preeclampsia using a PNA-based microarray.. Placenta 2013 Sep;34(9):799-804.
    doi: 10.1016/j.placenta.2013.06.006pubmed: 23830491google scholar: lookup
  27. Yu Y, Wang L, Liu T, Guan H. MicroRNA-204 suppresses trophoblast-like cell invasion by targeting matrix metalloproteinase-9.. Biochem Biophys Res Commun 2015 Jul 31;463(3):285-91.
    doi: 10.1016/j.bbrc.2015.05.052pubmed: 26003727google scholar: lookup
  28. Adamson B, Smogorzewska A, Sigoillot FD, King RW, Elledge SJ. A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response.. Nat Cell Biol 2012 Feb 19;14(3):318-28.
    doi: 10.1038/ncb2426pmc: PMC3290715pubmed: 22344029google scholar: lookup
  29. Kanhoush R, Beenders B, Perrin C, Moreau J, Bellini M, Penrad-Mobayed M. Novel domains in the hnRNP G/RBMX protein with distinct roles in RNA binding and targeting nascent transcripts.. Nucleus 2010 Jan-Feb;1(1):109-22.
    pmc: PMC3035123pubmed: 21327109doi: 10.4161/nucl.1.1.10857google scholar: lookup
  30. Wang Y, Arribas-Layton M, Chen Y, Lykke-Andersen J, Sen GL. DDX6 Orchestrates Mammalian Progenitor Function through the mRNA Degradation and Translation Pathways.. Mol Cell 2015 Oct 1;60(1):118-30.
    doi: 10.1016/j.molcel.2015.08.014pmc: PMC4592480pubmed: 26412305google scholar: lookup
  31. Rudolph LM, Bentley GE, Calandra RS, Paredes AH, Tesone M, Wu TJ, Micevych PE. Peripheral and Central Mechanisms Involved in the Hormonal Control of Male and Female Reproduction.. J Neuroendocrinol 2016 Jul;28(7).
    pmc: PMC5146987pubmed: 27329133doi: 10.1111/jne.12405google scholar: lookup
  32. Arendt LM, Kuperwasser C. Form and function: how estrogen and progesterone regulate the mammary epithelial hierarchy.. J Mammary Gland Biol Neoplasia 2015 Jun;20(1-2):9-25.
    doi: 10.1007/s10911-015-9337-0pmc: PMC4596764pubmed: 26188694google scholar: lookup
  33. Llovera M, Pichard C, Bernichtein S, Jeay S, Touraine P, Kelly PA, Goffin V. Human prolactin (hPRL) antagonists inhibit hPRL-activated signaling pathways involved in breast cancer cell proliferation.. Oncogene 2000 Sep 28;19(41):4695-705.
    doi: 10.1038/sj.onc.1203846pubmed: 11032019google scholar: lookup
  34. Rui H, Lebrun JJ, Kirken RA, Kelly PA, Farrar WL. JAK2 activation and cell proliferation induced by antibody-mediated prolactin receptor dimerization.. Endocrinology 1994 Oct;135(4):1299-306.
    doi: 10.1210/endo.135.4.7925093pubmed: 7925093google scholar: lookup
  35. Lee JH, Kim TH, Oh SJ, Yoo JY, Akira S, Ku BJ, Lydon JP, Jeong JW. Signal transducer and activator of transcription-3 (Stat3) plays a critical role in implantation via progesterone receptor in uterus.. FASEB J 2013 Jul;27(7):2553-63.
    pmc: PMC3688751pubmed: 23531596doi: 10.1096/fj.12-225664google scholar: lookup
  36. Suman P, Gupta SK. STAT3 and ERK1/2 cross-talk in leukaemia inhibitory factor mediated trophoblastic JEG-3 cell invasion and expression of mucin 1 and Fos.. Am J Reprod Immunol 2014 Jul;72(1):65-74.
    pubmed: 24716848doi: 10.1111/aji.12248google scholar: lookup
  37. Chen CY, Liu SH, Chen CY, Chen PC, Chen CP. Human placenta-derived multipotent mesenchymal stromal cells involved in placental angiogenesis via the PDGF-BB and STAT3 pathways.. Biol Reprod 2015 Oct;93(4):103.
    doi: 10.1095/biolreprod.115.131250pubmed: 26353894google scholar: lookup
  38. Wang W, Guo C, Zhu P, Lu J, Li W, Liu C, Xie H, Myatt L, Chen ZJ, Sun K. Phosphorylation of STAT3 mediates the induction of cyclooxygenase-2 by cortisol in the human amnion at parturition.. Sci Signal 2015 Oct 27;8(400):ra106.
    doi: 10.1126/scisignal.aac6151pubmed: 26508788google scholar: lookup
  39. Yu LJ, Wang B, Parobchak N, Roche N, Rosen T. STAT3 cooperates with the non-canonical NF-κB signaling to regulate pro-labor genes in the human placenta.. Placenta 2015 May;36(5):581-6.
    doi: 10.1016/j.placenta.2015.02.013pubmed: 25771405google scholar: lookup
  40. Lim W, Song G. Naringenin-induced migration of embrynoic trophectoderm cells is mediated via PI3K/AKT and ERK1/2 MAPK signaling cascades.. Mol Cell Endocrinol 2016 Jun 15;428:28-37.
    doi: 10.1016/j.mce.2016.03.018pubmed: 26994515google scholar: lookup
  41. Sferruzzi-Perri AN, López-Tello J, Fowden AL, Constancia M. Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation.. Proc Natl Acad Sci U S A 2016 Oct 4;113(40):11255-11260.
    doi: 10.1073/pnas.1602012113pmc: PMC5056071pubmed: 27621448google scholar: lookup
  42. Wahane SD, Hellbach N, Prentzell MT, Weise SC, Vezzali R, Kreutz C, Timmer J, Krieglstein K, Thedieck K, Vogel T. PI3K-p110-alpha-subtype signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2.. J Neurochem 2014 Jul;130(2):255-67.
    doi: 10.1111/jnc.12718pubmed: 24645666google scholar: lookup
  43. Amaral ME, Cunha DA, Anhê GF, Ueno M, Carneiro EM, Velloso LA, Bordin S, Boschero AC. Participation of prolactin receptors and phosphatidylinositol 3-kinase and MAP kinase pathways in the increase in pancreatic islet mass and sensitivity to glucose during pregnancy.. J Endocrinol 2004 Dec;183(3):469-76.
    doi: 10.1677/joe.1.05547pubmed: 15590973google scholar: lookup
  44. Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, Dreyfuss G, Eddy SR, Griffiths-Jones S, Marshall M, Matzke M, Ruvkun G, Tuschl T. A uniform system for microRNA annotation.. RNA 2003 Mar;9(3):277-9.
    pmc: PMC1370393pubmed: 12592000doi: 10.1261/rna.2183803google scholar: lookup

Citations

This article has been cited 7 times.
  1. Chen L, Wen H, Zhu Y, Wang F, Zhao L, Liang Q, Qu F. miR-373-3p Regulates the Proliferative and Migratory Properties of Human HTR8 Cells via SLC38A1 Modulation. Dis Markers 2022;2022:6582357.
    doi: 10.1155/2022/6582357pubmed: 35837487google scholar: lookup
  2. Liu L, Fang C, Sun Y, Liu W. Evaluation of key miRNAs during early pregnancy in Kazakh horse using RNA sequencing. PeerJ 2021;9:e10796.
    doi: 10.7717/peerj.10796pubmed: 33665012google scholar: lookup
  3. Smits K, Gansemans Y, Tilleman L, Van Nieuwerburgh F, Van De Velde M, Gerits I, Ververs C, Roels K, Govaere J, Peelman L, Deforce D, Van Soom A. Maternal Recognition of Pregnancy in the Horse: Are MicroRNAs the Secret Messengers?. Int J Mol Sci 2020 Jan 9;21(2).
    doi: 10.3390/ijms21020419pubmed: 31936511google scholar: lookup
  4. Loux SC, Dini P, El-Sheikh Ali H, Kalbfleisch T, Ball BA. Characterization of the placental transcriptome through mid to late gestation in the mare. PLoS One 2019;14(11):e0224497.
    doi: 10.1371/journal.pone.0224497pubmed: 31725741google scholar: lookup
  5. Qiu M, Li T, Wang B, Gong H, Huang T. miR-146a-5p Regulated Cell Proliferation and Apoptosis by Targeting SMAD3 and SMAD4. Protein Pept Lett 2020;27(5):411-418.
    doi: 10.2174/0929866526666190911142926pubmed: 31544687google scholar: lookup
  6. Zhou Y, Wang X, Zhang Y, Zhao T, Shan Z, Teng W. Circulating MicroRNA Profile as a Potential Predictive Biomarker for Early Diagnosis of Spontaneous Abortion in Patients With Subclinical Hypothyroidism. Front Endocrinol (Lausanne) 2018;9:128.
    doi: 10.3389/fendo.2018.00128pubmed: 29681887google scholar: lookup
  7. Cheng M, Zhou Y, Wang Q, Luo B, Lai Y, Cheng J, Zhang X, Huang Y, Li D. MicroRNA expression profiles in plasma exosomes of late pregnant giant pandas. Mol Biol Rep 2024 Oct 18;51(1):1068.
    doi: 10.1007/s11033-024-09988-3pubmed: 39422788google scholar: lookup
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