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Veterinary research2021; 52(1); 103; doi: 10.1186/s13567-021-00972-4

Transcriptomic analysis of equine chorioallantois reveals immune networks and molecular mechanisms involved in nocardioform placentitis.

Abstract: Nocardioform placentitis (NP) continues to result in episodic outbreaks of abortion and preterm birth in mares and remains a poorly understood disease. The objective of this study was to characterize the transcriptome of the chorioallantois (CA) of mares with NP. The CA were collected from mares with confirmed NP based upon histopathology, microbiological culture and PCR for Amycolatopsis spp. Samples were collected from the margin of the NP lesion (NPL, n = 4) and grossly normal region (NPN, n = 4). Additionally, CA samples were collected from normal postpartum mares (Control; CRL, n = 4). Transcriptome analysis identified 2892 differentially expressed genes (DEGs) in NPL vs. CRL and 2450 DEGs in NPL vs. NPN. Functional genomics analysis elucidated that inflammatory signaling, toll-like receptor signaling, inflammasome activation, chemotaxis, and apoptosis pathways are involved in NP. The increased leukocytic infiltration in NPL was associated with the upregulation of matrix metalloproteinase (MMP1, MMP3, and MMP8) and apoptosis-related genes, such as caspases (CASP3 and CASP7), which could explain placental separation associated with NP. Also, NP was associated with downregulation of several placenta-regulatory genes (ABCG2, GCM1, EPAS1, and NR3C1), angiogenesis-related genes (VEGFA, FLT1, KDR, and ANGPT2), and glucose transporter coding genes (GLUT1, GLUT10, and GLUT12), as well as upregulation of hypoxia-related genes (HIF1A and EGLN3), which could elucidate placental insufficiency accompanying NP. In conclusion, our findings revealed for the first time, the key regulators and mechanisms underlying placental inflammation, separation, and insufficiency during NP, which might lead to the development of efficacious therapies or diagnostic aids by targeting the key molecular pathways.
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Publication Date: 2021-07-08 PubMed ID: 34238364PubMed Central: PMC8268225DOI: 10.1186/s13567-021-00972-4Google 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.

The research article focuses on a comprehensive transcriptomic analysis of the equine chorioallantois in nocardioform placentitis, a disease responsible for abortions and preterm birth in mares. The study brings out the immune responses, key gene interactions, and molecular mechanisms involved in the disease, possibly directing the development of targeted therapeutic interventions.

Research Objective and Methodology

The core objective of the research was to understand the genetic aspects of nocardioform placentitis (NP) through the transcriptome analysis of the chorioallantois (CA), a crucial structure involved in gas and nutrient exchange during pregnancy. Chorioallantois samples were collected from mares diagnosed with NP (both from the lesion’s region and the grossly normal region). For comparison, similar samples were collected from normal post-birth mares.

Key Findings and Analysis

  • Transcriptome analysis revealed a total of 2892 and 2450 differentially expressed genes when compared between the NP lesion (NPL) and normal postpartum samples, and between NPL and the grossly normal region in NP (NPN) respectively.
  • Functional genomics pointed at key pathways like inflammatory signaling, toll-like receptor signaling, inflammasome activation, chemotaxis, and apoptosis being integral to NP pathogenesis.
  • An increase in leukocytic infiltration in NPL associated with the upregulation of certain genes like MMP1, MMP3, MMP8, and apoptosis-related genes (CASP3 and CASP7), providing a plausible explanation for placental separation correlated with NP.
  • The study also observed the downregulation of several placenta-regulatory genes, angiogenesis-related genes, and glucose transporter genes, and upregulation of hypoxia-related genes. These changes could decipher the origins of placental insufficiency seen in NP cases.

    • Conclusions and Significance

  • The research provides first-hand insight into molecular mechanisms, key regulators, and altered gene expressions involved in placental inflammation, separation, and insufficiency during NP.
  • These findings can act as a platform to develop effective therapies and diagnostic aids for NP, targeting the abnormalities in key molecular pathways.

    • Cite This Article

    APA
    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. (2021). Transcriptomic analysis of equine chorioallantois reveals immune networks and molecular mechanisms involved in nocardioform placentitis. Vet Res, 52(1), 103. https://doi.org/10.1186/s13567-021-00972-4

    Publication

    Veterinary research
    ISSN: 1297-9716
    NlmUniqueID: 9309551
    Country: England
    Language: English
    Volume: 52
    Issue: 1
    Pages: 103
    PII: 103

    Researcher Affiliations

    El-Sheikh Ali, Hossam
    • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
    • Theriogenology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
    Loux, Shavahn C
    • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
    Kennedy, Laura
    • UK Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, KY, 40546, USA.
    Scoggin, Kirsten E
    • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
    Dini, Pouya
    • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
    Fedorka, Carleigh E
    • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
    Kalbfleisch, Theodore S
    • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
    Esteller-Vico, Alejandro
    • Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, USA.
    Horohov, David W
    • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA.
    Erol, Erdal
    • UK Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, KY, 40546, USA.
    Carter, Craig N
    • UK Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, KY, 40546, USA.
    Smith, Jackie L
    • UK Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, KY, 40546, USA.
    Ball, Barry A
    • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, 40546, USA. b.a.ball@uky.edu.

    MeSH Terms

    • Actinobacteria / isolation & purification
    • Amycolatopsis / isolation & purification
    • Animals
    • Chorioamnionitis / immunology
    • Chorioamnionitis / microbiology
    • Chorioamnionitis / veterinary
    • Female
    • Gene Expression Profiling / veterinary
    • Gram-Positive Bacterial Infections / immunology
    • Gram-Positive Bacterial Infections / microbiology
    • Gram-Positive Bacterial Infections / veterinary
    • Horse Diseases / immunology
    • Horse Diseases / microbiology
    • Horses
    • Pregnancy
    • Transcriptome

    Conflict of Interest Statement

    The authors declare that they have no competing interests.

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    Citations

    This article has been cited 6 times.
    1. Fedorka CE, Ali HE, Troedsson MHT. Galectins in Equine Placental Disease. Vet Sci 2023 Mar 13;10(3).
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    3. 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).
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    4. 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.
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    5. 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).
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    6. 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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