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Reproduction (Cambridge, England)2021; 161(6); 603-621; doi: 10.1530/REP-21-0008

Equine cervical remodeling during placentitis and the prepartum period: a transcriptomic approach.

Abstract: Cervical remodeling is a critical component in both term and preterm labor in eutherian mammals. However, the molecular mechanisms underlying cervical remodeling remain poorly understood in the mare. The current study compared the transcriptome of the equine cervix (cervical mucosa (CM) and stroma (CS)) during placentitis (placentitis group, n = 5) and normal prepartum mares (prepartum group, n = 3) to normal pregnant mares (control group, n = 4). Transcriptome analysis identified differentially expressed genes (DEGs) during placentitis (5310 in CM and 907 in CS) and during the normal prepartum period (189 in CM and 78 in CS). Our study revealed that cervical remodeling during placentitis was dominated by inflammatory signaling as reflected by the overrepresented toll-like receptor signaling, interleukin signaling, T cell activation, and B cell activation pathways. These pathways were accompanied by upregulation of several proteases, including matrix metalloproteinases (MMP1, MMP2, and MMP9), cathepsins (CTSB, CTSC, and CTSD) and a disintegrin and metalloproteinase with thrombospondin type 1 motifs (ADAMTS1, ADAMTS4, and ADAMTS5), which are crucial for degradation of cervical collagens during remodeling. Cervical remodeling during placentitis was also associated with upregulation of water channel-related transcripts (AQP9 and RLN), angiogenesis-related transcripts (NOS3, ENG1, THBS1, and RAC2), and aggrecan (ACAN), a hydrophilic glucosaminoglycan, with subsequent cervical hydration. The normal prepartum cervix was associated with upregulation of ADAMTS1, ADAMTS4, NOS3 and THBS1, which might reflect an early stage of cervical remodeling taking place in preparation for labor. In conclusion, our findings revealed the possible key regulators and mechanisms underlying equine cervical remodeling during placentitis and the normal prepartum period.
Publication Date: 2021-05-05 PubMed ID: 33780349DOI: 10.1530/REP-21-0008Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research explores the molecular mechanisms underlying cervical remodeling in horses, particularly during placentitis (inflammation of the placenta) and the normal prepartum period. This has been done by examining gene expression in the cervix, revealing that inflammation pathways and degradation proteins play a significant role, with certain genes being upregulated in these contexts.

Understanding Cervical Remodeling

In their research, the scientists looked into the cervical remodeling processes – a vital aspect for mammals both in full-term and preterm labor. However, the molecular mechanisms driving cervical remodeling in horses (mares) are yet to be fully understood. To better comprehend these mechanisms, the scholars compared the transcriptome of the cervical mucosa (CM) and stroma (CS) of mares during placentitis, normal prepartum periods, and in a control group.

  • Cervical remodeling is an essential process in labor, allowing for the passage of fetuses. Despite its importance, the molecular mechanisms that allow this process to happen are poorly understood.

Remodeling Research Findings

After analyzing their research data, the scientists found significant differences in gene expression at various stages.

  • The researchers identified thousands of differentially expressed genes (DEGs) during placentitis and the normal prepartum period. These are genes whose expression – the process by which information from a gene is used to create a functional product like a protein – changes under different conditions.
  • In the case of placentitis, remodeling was dominated by inflammation pathways. This was shown by the overrepresented toll-like receptor signaling, interleukin signaling, T cell and B cell activation pathways.
  • Inflammatory pathways are parts of the immune system that respond to injury or disease. An overrepresentation of these pathways during placentitis suggests that the inflammation of the placenta triggers molecular changes that ultimately lead to remodeling.
  • This remodeling was coupled with increased expression of several proteases, enzymes that break down proteins. This includes matrix metalloproteinases (MMP1, MMP2, and MMP9), cathepsins (CTSB, CTSC, and CTSD), and a disintegrin and metalloproteinase with thrombospondin type 1 motifs (ADAMTS1, ADAMTS4, and ADAMTS5) that play a critical role in the degradation of cervical collagens during remodeling.

Importance of the Study

The study is critical because it sheds light on the underlying mechanisms of cervical remodeling, a crucial process for successful labor in horses.

  • By examining gene expression in the cervix, the researchers have thrown light on the molecular factors that drive cervical remodeling.
  • The findings suggest that certain processes, such as inflammation and protein degradation, are crucial for cervical remodeling. Therefore, disturbances to these processes could potentially lead to complications during labor.
  • The study also identified a number of gene transcripts that were upregulated – meaning their expression increased – during cervical remodeling. This might reflect an early stage of remodeling in preparation for labor. These genes and their associated proteins could potentially serve as biomarkers for cervical remodeling, providing a way to monitor the process and intervene if required.

Cite This Article

APA
El-Sheikh Ali H, Scoggin KE, Ruby R, Loynachan A, Boakari Y, Fernandes C, Dini P, Fedorka CE, Loux SC, Esteller-Vico A, Ball BA. (2021). Equine cervical remodeling during placentitis and the prepartum period: a transcriptomic approach. Reproduction, 161(6), 603-621. https://doi.org/10.1530/REP-21-0008

Publication

ISSN: 1741-7899
NlmUniqueID: 100966036
Country: England
Language: English
Volume: 161
Issue: 6
Pages: 603-621
PII: REP-21-0008

Researcher Affiliations

El-Sheikh Ali, Hossam
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
  • Theriogenology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
Scoggin, Kirsten E
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Ruby, Rebecca
  • UK Veterinary Diagnostic Laboratory, University of Kentucky, Kentucky, USA.
Loynachan, Alan
  • UK Veterinary Diagnostic Laboratory, University of Kentucky, Kentucky, USA.
Boakari, Yatta
  • Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn, Alabama, USA.
Fernandes, Claudia
  • Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Dini, Pouya
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA.
Fedorka, Carleigh Elizabeth
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Loux, Shavahn C
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Esteller-Vico, Alejandro
  • Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, Tennessee, USA.
Ball, Barry A
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.

MeSH Terms

  • Animals
  • Cervix Uteri / physiopathology
  • Female
  • Gene Expression Regulation
  • Horse Diseases / genetics
  • Horse Diseases / metabolism
  • Horse Diseases / pathology
  • Horses
  • Placenta / metabolism
  • Placenta Diseases / genetics
  • Placenta Diseases / metabolism
  • Placenta Diseases / pathology
  • Placenta Diseases / veterinary
  • Pregnancy
  • Transcriptome

Citations

This article has been cited 1 times.
  1. Fedorka CE, Ali HE, Troedsson MHT. Galectinology of Equine Pregnancy.. Animals (Basel) 2022 Dec 29;13(1).
    doi: 10.3390/ani13010129pubmed: 36611738google scholar: lookup