Transcriptomic analysis reveals the key regulators and molecular mechanisms underlying myometrial activation during equine placentitis†.
Abstract: The key event in placentitis-induced preterm labor is myometrial activation with the subsequent initiation of labor. However, the molecular mechanisms underlying myometrial activation are not fully understood in the mares. Therefore, the equine myometrial transcriptome was characterized during placentitis (290.0 ± 1.52 days of GA, n = 5) and the prepartum period (330 days of GA, n = 3) in comparison to normal pregnant mares (289.8 ± 2.18 days of GA, n = 4). Transcriptome analysis identified 596 and 290 DEGs in the myometrium during placentitis and the prepartum period, respectively, with 138 DEGs in common. The placentitis DEGs included eight genes (MMP1, MMP8, S100A9, S100A8, PI3, APOBEC3Z1B, RETN, and CXCL2) that are exclusively expressed in the inflamed myometrium. Pathway analysis elucidated that inflammatory signaling, Toll-like receptor signaling, and apoptosis pathways dominate myometrial activation during placentitis. The prepartum myometrium was associated with overexpression of inflammatory signaling, oxidative stress, and 5-hydroxytryptamine degradation. Gene ontology enrichment analysis identified several chemoattractant factors in the myometrium during placentitis and prepartum period, including CCL2, CXCL1, CXCL3, and CXCL6 in common. Upstream regulator analysis revealed 19 potential upstream regulators in placentitis dataset including transcription regulators (E2F1, FOXM1, HIF1A, JUNB, NFKB1A, and STAT1), transmembrane receptors (FAS, ICAM1, SELP, TLR2, and TYROBP), growth factors (HGF and TGFB3), enzymes (PTGS2 and PRKCP), and others (S100A8, S100A9, CD44, and C5AR1). Additionally, three upstream regulators (STAT3, EGR1, and F2R) were identified in the prepartum dataset. These findings revealed the key regulators and pathways underlying myometrial activation during placentitis, which aid in understanding the disease and facilitate the development of efficacious therapies.
© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Publication Date: 2020-02-18 PubMed ID: 32065222DOI: 10.1093/biolre/ioaa020Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article uncovers essential molecular regulators and mechanisms involved in myometrial activation, a crucial step in preterm labor induced by placentitis, in mares. The findings came from the analysis of the transcriptome in mares during placentitis, the prepartum period, and normal pregnancy.
Research Methodology
- The researchers characterized the transcriptome of the equine myometrium in three different stages: during placentitis, the prepartum period, and normal pregnancy.
- The number of differentially expressed genes (DEGs) in the myometrium were found in each stage, with a noteworthy focus on genes that were exclusively expressed during placentitis.
Key Findings
- Out of the identified DEGs, 596 were found in placentitis and 290 in the prepartum period, with 138 DEGs being common in both stages.
- Eight genes (MMP1, MMP8, S100A9, S100A8, PI3, APOBEC3Z1B, RETN, and CXCL2) that exclusively expressed in the inflamed myometrium were identified during placentitis.
- Pathway analysis revealed that inflammatory signaling, Toll-like receptor signaling, and apoptosis pathways are predominantly involved in myometrial activation during placentitis.
- In the prepartum period, overexpression of inflammatory signaling, oxidative stress, and 5-hydroxytryptamine degradation was noted.
- Several chemoattractant factors common in placentitis and prepartum period were identified.
- The study detected 19 potential upstream regulators in placentitis dataset and three in the prepartum dataset.
Implications of the Study
- The findings of this study provide a deeper understanding of how myometrial activation influences preterm labor resulting from placentitis in horses.
- The knowledge of the key regulators and pathways involved in this process can facilitate the development of effective therapies for placentitis and reduce the occurrence of preterm births.
Cite This Article
APA
El-Sheikh Ali H, Boakari YL, Loux SC, Dini P, Scoggin KE, Esteller-Vico A, Kalbfleisch T, Ball BA.
(2020).
Transcriptomic analysis reveals the key regulators and molecular mechanisms underlying myometrial activation during equine placentitis†.
Biol Reprod, 102(6), 1306-1325.
https://doi.org/10.1093/biolre/ioaa020 Publication
Researcher Affiliations
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
- Theriogenology Department, Faculty of Veterinary Medicine, University of Mansoura, Dakahlia, Mansoura, Egypt.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
- Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, Tennessee, Knoxville, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
MeSH Terms
- Animals
- Female
- Genomics
- Horse Diseases / metabolism
- Horses
- Immunoblotting
- Immunohistochemistry
- Myometrium / metabolism
- Placenta Diseases / metabolism
- Placenta Diseases / veterinary
- Pregnancy
- Transcriptome
Citations
This article has been cited 8 times.- Fedorka CE, Ali HE, Troedsson MHT. Galectins in Equine Placental Disease. Vet Sci 2023 Mar 13;10(3).
- El-Sheikh Ali H, Loux SC, Kennedy L, Scoggin KE, Dini P, Fedorka CE, Kalbfleisch TS, Esteller-Vico A, Horohov DW, Erol E, Carter CN, Smith JL, Ball BA. Transcriptomic analysis of equine chorioallantois reveals immune networks and molecular mechanisms involved in nocardioform placentitis. Vet Res 2021 Jul 8;52(1):103.
- Laseca N, Anaya G, Peña Z, Pirosanto Y, Molina A, Demyda Peyrás S. Impaired Reproductive Function in Equines: From Genetics to Genomics. Animals (Basel) 2021 Feb 3;11(2).
- Scoggin KE, Rakha SI, Abdellatif AM, Adlan F, Helmy YA, Ruby R, Ball B, Boakari Y, Ali HE. Activation of the S100A8/A9 Alarmin Amplifies Inflammatory Pathways in Equine Ascending Placentitis. Int J Mol Sci 2026 Feb 4;27(3).
- Scoggin KE, Adlan F, Fedorka CE, Rakha SI, Stout TAE, Troedsson MHT, Ali HE. Gestation-Stage Related Changes in the IGF System Components in the Equine Placenta. Biomolecules 2025 Aug 6;15(8).
- Marchio SP, El-Sheikh Ali H, Scott MA, Barbosa Fernandes C, Scoggin KE, Troedsson M, Boakari Y. Decoding the amniotic membrane transcriptome during equine ascending placentitis. Sci Rep 2025 Aug 21;15(1):30714.
- Piotrowska-Tomala KK, Szóstek-Mioduchowska AZ, Drzewiecka EM, Jonczyk AW, Wójtowicz A, Wrobel MH, Ferreira-Dias G, Skarzynski DJ. Prostaglandin pathways in equine myometrium regulations: endometrosis progression. Front Vet Sci 2024;11:1479508.
- Morales-Vázquez MM, Meza-Serrano E, Lara-Pereyra I, Acuña-González RJ, Alonso-Morales R, Hayen-Valles S, Boeta AM, Zarco L, Lozano-Cuenca J, López-Canales JS, Flores-Herrera H. Equine Placentitis in Mares Induces the Secretion of Pro-Inflammatory Cytokine eIL-1β and the Active Extracellular Matrix Metalloproteinase (MMP)-9. Vet Sci 2023 Aug 22;10(9).
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