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Transcriptomic analysis of equine placenta reveals key regulators and pathways involved in ascending placentitis†.
Abstract: Improved understanding of the molecular mechanisms underlying ascending equine placentitis holds the potential for the development of new diagnostic tools and therapies to forestall placentitis-induced preterm labor. The current study characterized the equine placental transcriptome (chorioallantois [CA] and endometrium [EN]) during placentitis (placentitis group, n = 6) in comparison to gestationally-matched controls (control group, n = 6). Transcriptome analysis identified 2953 and 805 differentially expressed genes in CA and EN during placentitis, respectively. Upstream regulator analysis revealed the central role of toll-like receptors (TLRs) in triggering the inflammatory signaling, and consequent immune-cell chemotaxis. Placentitis was associated with the upregulation of matrix metalloproteinase (MMP1, MMP2, and MMP9) and apoptosis-related genes such as caspases (CASP3, CASP4, and CASP7) in CA. Also, placentitis was associated with downregulation of transcripts coding for proteins essential for placental steroidogenesis (SRD5A1 and AKR1C1), progestin signaling (PGRMC1 and PXR) angiogenesis (VEGFA, VEGFR2, and VEGFR3), and nutrient transport (GLUT12 and SLC1A4), as well as upregulation of hypoxia-related genes (HIF1A and EGLN3), which could explain placental insufficiency during placentitis. Placentitis was also associated with aberrant expression of several placenta-regulatory genes, such as PLAC8, PAPPA, LGALS1, ABCG2, GCM1, and TEPP, which could negatively affect placental functions. In conclusion, our findings revealed for the first time the key regulators and mechanisms underlying placental inflammation, separation, and insufficiency during equine placentitis, which might lead to the development of efficacious therapies or diagnostic aids by targeting the key molecular pathways.
© 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: 2020-12-22 PubMed ID: 33345276DOI: 10.1093/biolre/ioaa209Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
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.
The research is an investigation of the molecular mechanisms involved in equine placentitis, a condition leading to preterm labor in horses, with the hope of developing better diagnostic tools and treatments. The study analyzed changes in gene expression in the equine placenta during placentitis, highlighting molecular pathways involved.
Objective and Methodology
- This research aimed to understand the molecular mechanisms of ascending equine placentitis by characterizing the equine placental transcriptome (gene expression profile) during the disease.
- To do so, the researchers compared the equine placental transcriptome during placentitis with those of gestationally-matched controls. Specifically, they analyzed gene expression in the chorioallantois (CA) and endometrium (EN) regions of the placenta.
Findings
- Researchers found significant differences in gene expression during placentitis. Specifically, 2953 and 805 genes were differentially expressed in the CA and EN regions, respectively.
- The research highlighted the crucial role of toll-like receptors (TLRs) in triggering inflammation and immune-cell movement during placentitis.
- Placentitis was associated with the upregulation (increased expression) of matrix metalloproteinase (MMP) and apoptosis-related genes such as caspases, particularly in the CA.
- Meanwhile, placentitis was associated with downregulation (decreased expression) of genes coding for proteins essential for steroidogenesis, progestin signaling, and angiogenesis, among others. This could impact placental functions and health.
- Furthermore, the elevation of hypoxia-related genes, potentially explaining the occurrence of placental insufficiency during placentitis, was observed.
- Placentitis was also associated with changes in the expression of several gene regulators crucial for placental health and functions, including PLAC8, PAPPA, LGALS1, ABCG2, GCM1, and TEPP.
Conclusion
- This study provides insight into the key regulators and molecular mechanisms involved in equine placentitis, advancing the understanding of this condition.
- The results could potentially guide the development of more effective therapies or diagnostic aids targeting these key molecular pathways in the future.
Cite This Article
APA
El-Sheikh Ali H, Dini P, Scoggin K, Loux S, Fedorka C, Boakari Y, Norris J, Esteller-Vico A, Kalbfleisch T, Ball B.
(2020).
Transcriptomic analysis of equine placenta reveals key regulators and pathways involved in ascending placentitis†.
Biol Reprod, 104(3), 638-656.
https://doi.org/10.1093/biolre/ioaa209 Publication
Researcher Affiliations
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Theriogenology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
MeSH Terms
- Animals
- Down-Regulation
- Female
- Gene Expression Regulation / immunology
- Gene Expression Regulation / physiology
- Horse Diseases / metabolism
- Horses
- Immunohistochemistry
- Placenta / metabolism
- Placenta Diseases / metabolism
- Placenta Diseases / veterinary
- Pregnancy
- Streptococcal Infections / metabolism
- Streptococcal Infections / microbiology
- Streptococcal Infections / pathology
- Streptococcal Infections / veterinary
- Streptococcus equi
- Transcriptome
- Up-Regulation
Citations
This article has been cited 11 times.- Fedorka CE, Ali HE, Troedsson MHT. Galectins in Equine Placental Disease. Vet Sci 2023 Mar 13;10(3).
- Fedorka CE, Ali HE, Troedsson MHT. Galectinology of Equine Pregnancy. Animals (Basel) 2022 Dec 29;13(1).
- Sun L, Sun Z, Wang Q, Zhang Y, Jia Z. Role of nuclear receptor PXR in immune cells and inflammatory diseases. Front Immunol 2022;13:969399.
- Mao M, Cheng Y, Yang J, Chen Y, Xu L, Zhang X, Li Z, Chen C, Ju S, Zhou J, Wang L. Multifaced roles of PLAC8 in cancer. Biomark Res 2021 Oct 9;9(1):73.
- 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.
- 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).
- van Heule M, Verstraete M, Norris JK, Graniczkowsa KB, Scoggin KE, Ali HE, Ball BA, De Spiegelaere W, Daels P, Weimer BC, Dini P. Beyond nocardioform: Transcriptionally active microbes and host responses in equine mucoid placentitis. Equine Vet J 2026 Mar;58(2):601-618.
- 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.
- Kabir A, Lamichhane B, Habib T, Adams A, El-Sheikh Ali H, Slovis NM, Troedsson MHT, Helmy YA. Antimicrobial Resistance in Equines: A Growing Threat to Horse Health and Beyond-A Comprehensive Review. Antibiotics (Basel) 2024 Jul 29;13(8).
- Bae JW, Hwang JM, Yoon M, Kwon WS. Bifenthrin Diminishes Male Fertility Potential by Inducing Protein Defects in Mouse Sperm. Toxics 2024 Jan 10;12(1).
- 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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