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.
Digital Object Identifier (DOI)
This study is supported by the Koller Priority Response Fund and the Albert G. Clay Endowment of the University of Kentucky.
The current RNA-seq data was deposited in the Gene Expression Omnibus (GEO; GSE154637) repository.
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.
Additional file 1. Summary of the bioinformatics and functional genomics pipeline used in the current study
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Additional file 2. Clinical and pathological findings in for all mares included in the current study
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Additional file 3. Read counts and mapping quality of Illumina RNA-sequencing dataset from equine chorioallantois (CA) retrieved from CRL, NPL, and NPN
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Additional file 4. Differentially expressed genes (DEGs) in equine chorioallantois during nocardioform placentitis (NPL vs. CRL and NPL vs. NPN sets)
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Additional file 5. Potential upstream regulators in equine chorioallantois (CA) during nocardioform placentitis (NP) as identified by upstream regulator analysis performed on Ingenuity Pathway Analysis (IPA) using DEG
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Additional file 6. Weighted gene expression co-expression network analysis (WGCNA) of DEGs in equine chorioallantois (CA) during nocardioform placentitis dataset
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Additional file 7. List of predicted ligand and receptor pairs and their expression patterns in equine chorioallantois (CA) during nocardioform placentitis dataset