Transcriptomic Analysis of Equine Chorioallantois Reveals Immune Networks and Molecular Mechanisms Involved in Nocardioform Placentitis

Authors

Hossam El-Sheikh Ali, University of Kentucky
Shavahn C. Loux, University of KentuckyFollow
Laura Kennedy, University of KentuckyFollow
Kirsten E. Scoggin, University of KentuckyFollow
Pouya Dini, University of KentuckyFollow
Carleigh E. Fedorka, University of KentuckyFollow
Theodore S. Kalbfleisch, University of KentuckyFollow
Alejandro Esteller-Vico, University of Tennessee, Knoxville
David W. Horohov, University of KentuckyFollow
Erdal Erol, University of KentuckyFollow
Craig N. Carter, University of KentuckyFollow
Jackie L. Smith, University of Kentucky
Barry A. Ball, University of KentuckyFollow

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.

Document Type

Article

Publication Date

7-8-2021

Notes/Citation Information

Published in Veterinary Research, v. 52, issue 1, article no. 103.

© The Author(s) 2021

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Digital Object Identifier (DOI)

https://doi.org/10.1186/s13567-021-00972-4

Funding Information

This study is supported by the Koller Priority Response Fund and the Albert G. Clay Endowment of the University of Kentucky.

Related Content

The current RNA-seq data was deposited in the Gene Expression Omnibus (GEO; GSE154637) repository.

Repository Citation

El-Sheikh Ali, Hossam; Loux, Shavahn C.; Kennedy, Laura; Scoggin, Kirsten E.; Dini, Pouya; Fedorka, Carleigh E.; Kalbfleisch, Theodore S.; Esteller-Vico, Alejandro; Horohov, David W.; Erol, Erdal; Carter, Craig N.; Smith, Jackie L.; and Ball, Barry A., "Transcriptomic Analysis of Equine Chorioallantois Reveals Immune Networks and Molecular Mechanisms Involved in Nocardioform Placentitis" (2021). Maxwell H. Gluck Equine Research Center Faculty Publications. 59.
https://uknowledge.uky.edu/gerc_facpub/59