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

• Published in: Veterinary research (Paris) Vol. 52; no. 1; pp. 1 - 103
• Main Authors: 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, Ball, Barry A
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 08-07-2021; BioMed Central; BMC
• Subjects: Abortion; Amycolatopsis spp; Analysis; Bacterial infections; Bioinformatics; Chorioallantois; Equine; Gene expression; Genes; Genomics; Histochemistry; Infants (Premature); Infections; Inflammation; Life Sciences; Ligands; Medical research; Medicine, Experimental; Nocardioform placentitis; Pathogenesis; Pathophysiology; Placenta; Proteins; Transcriptome; United States > US; Kentucky; Equine; Amycolatopsis spp; Chorioallantois; Transcriptome; Nocardioform placentitis
• ISSN: 1297-9716; 0928-4249; 1297-9716
• DOI: 10.1186/s13567-021-00972-4

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.