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Home / Equine Research Bank / Theriogenology / Uterine cervix as a fundamental part of the pathogenesis of ...
Theriogenology2019; 145; 167-175; doi: 10.1016/j.theriogenology.2019.10.017

Uterine cervix as a fundamental part of the pathogenesis of pregnancy loss associated with ascending placentitis in mares.

Abstract: Anatomical and molecular changes in the cervical barrier in women are a fundamental part of the pathogenesis of pregnancy loss associated with chorioamnionitis. However, there is little information regarding changes in the cervix associated with ascending infection in pregnant mares. To better characterize morphological and molecular changes in the cervix during placentitis, we examined full thickness histology and mRNA expression for a number of inflammatory and endocrine factors in the mucosa and stroma of the cervix of mares (n = 5) after experimental induction of placentitis via transcervical inoculation with Streptococcus equi ssp zooepidemicus at approximately 290d of gestation. Gestationally age-matched mares (n = 4) served as controls. Target transcripts included steroid receptors (PGR, ESR1 and 2), OXTR, prostaglandins synthases and receptors (PTGS1, PTGS2, PGES, PGFS, PTGER2 and PTGER4), cytokines (IL1b, IL6, CLCX8, IL10 and TNFα) and acute phase proteins (SAA). Histologically, a marked modification in the cervical epithelia and stroma was characterizing cervicitis. Additionally, the mRNA expression of IL1β, IL6, CXCL8, SAA and PTGS2 was greater (P < 0.05) in both mucosa and stroma of the inoculated mares; whereas TNFα, IL10 and PGES were upregulated (P < 0.05) only in the cervical mucosa. Progesterone receptor, ESR1 and PTGER4 were upregulated in the cervical stroma of placentitis mares. In conclusion, the cervical response to placentitis was characterized by an upregulation of inflammatory cytokines that was accompanied by induction of PTGS2 and PGES. Further, receptors known to be associated with relaxation of the cervix in other species (ESR1 and PTGER4) were upregulated in the cervical stroma of placentitis mares. These findings indicate that the cervix is not only a physical barrier but that it has an active role in the pathogenesis of ascending placentitis.
Copyright © 2019 Elsevier Inc. All rights reserved.
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Publication Date: 2019-10-14 PubMed ID: 31732164DOI: 10.1016/j.theriogenology.2019.10.017Google Scholar: Lookup
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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 explores how the uterus in mares responds to pregnancy loss due to an ascending infection, known as placentitis. By inducing placentitis in pregnant mares and studying the molecular and anatomical changes, the study finds that the uterus plays a significant role in the progression of placentitis.

Objective of the Study

  • The key objective of this research was to elucidate morphological and molecular changes in the cervix during placentitis in pregnant mares. This was accomplished by analyzing full thickness histology and mRNA expression of various inflammatory and endocrine factors in the cervical mucosa and stroma of the mares.

Methodology

  • The researchers used a sample size of five pregnant mares where placentitis was experimentally induced via transcervical inoculation with Streptococcus equi ssp at roughly 290 days of gestation. Four gestational age-matched mares were used as controls.
  • They targeted specific gene transcripts related to cervical inflammation including steroid receptors, prostaglandin synthases and receptors, cytokines, and acute phase proteins to document any variations in their transcription.

Key Findings

  • The researchers found significant changes in the cervical epithelia and stroma, indicative of cervicitis, a potentially severe condition of the cervix.
  • mRNA expression for genes linked to inflammation (IL1β, IL6, CXCL8, SAA) and prostaglandin synthesis (PTGS2) was significantly higher in both the mucosa and stroma of inoculated mares, suggesting an active immune response.
  • An upregulation of genes (TNFα, IL10, PGES) was also observed, but only in the cervical mucosa.
  • Receptors associated with cervical relaxation in other species, namely, progesterone receptor, ESR1 and PTGER4, were upregulated in the cervical stroma of mares with placentitis.

Conclusion

  • The results suggest that the cervix plays a more active role in defending against placentitis, as evidenced by the upregulation of inflammatory cytokines and other factors. This goes beyond its understood role as a physical barrier to the ascending infection.

Cite This Article

APA
Fernandes CB, Ball BA, Loux SC, Boakari YL, Scoggin KE, El-Sheikh Ali H, Cogliati B, Esteller-Vico A. (2019). Uterine cervix as a fundamental part of the pathogenesis of pregnancy loss associated with ascending placentitis in mares. Theriogenology, 145, 167-175. https://doi.org/10.1016/j.theriogenology.2019.10.017

Publication

Theriogenology
ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 145
Pages: 167-175
PII: S0093-691X(19)30470-4

Researcher Affiliations

Fernandes, C B
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY, 40546, USA; Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of São Paulo, 05508-270, Brazil.
Ball, B A
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY, 40546, USA.
Loux, S C
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY, 40546, USA.
Boakari, Y L
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY, 40546, USA.
Scoggin, K E
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY, 40546, USA.
El-Sheikh Ali, H
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY, 40546, USA; Theriogenology Department, Faculty of Veterinary Medicine, University of Mansoura, 35516, Egypt.
Cogliati, B
  • Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, 05508-270, Brazil.
Esteller-Vico, A
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY, 40546, USA. Electronic address: a.esteller-vico@utk.edu.

MeSH Terms

  • Abortion, Veterinary
  • Animals
  • Cervix Uteri / pathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation
  • Horse Diseases / pathology
  • Horses
  • Placenta Diseases / veterinary
  • Pregnancy
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Receptors, Oxytocin / genetics
  • Receptors, Oxytocin / metabolism
  • Receptors, Prostaglandin / genetics
  • Receptors, Prostaglandin / metabolism
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism
  • Serum Amyloid A Protein / metabolism

Conflict of Interest Statement

Declaration of competing interest The authors declare that there are no conflicts of interests.

Citations

This article has been cited 6 times.
  1. Ashraf R, Rashid S, Rasheed I, Asif S. Early embryonic death in equines and camelids. Open Vet J 2022 Nov-Dec;12(6):903-909.
    doi: 10.5455/OVJ.2022.v12.i6.16pubmed: 36777062google scholar: lookup
  2. 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).
    doi: 10.3390/biom15081135pubmed: 40867581google scholar: lookup
  3. 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.
    doi: 10.1038/s41598-025-16671-5pubmed: 40841585google scholar: lookup
  4. 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).
    doi: 10.3390/antibiotics13080713pubmed: 39200013google scholar: lookup
  5. Zdrojkowski Ł, Pawliński B, Skierbiszewska K, Jasiński T, Domino M. Assessment of Connective Tissue in the Equine Uterus and Cervix: Review of Clinical Impact and Staining Options. Animals (Basel) 2024 Jan 3;14(1).
    doi: 10.3390/ani14010156pubmed: 38200887google scholar: lookup
  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).
    doi: 10.3390/vetsci10090532pubmed: 37756054google scholar: lookup
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