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.
Highlights
Nocardioform placentitis (NP) is defined as a focal mucoid placental inflammation in which the bacterial infection is limited to the chorionic surface of the ventralEl‐Sheikh Ali et al Vet Res (2021) 52:103 and insufficiency with large areas of the chorion that may be involved with the lesion [1]
The current study presents a distinct transcriptome signature of equine NP (Amycolatopsis spp.) and adds to the understanding of the key regulators and molecular mechanisms involved in the disease
Our results revealed that NP is dominated by Toll-like receptor signaling, inflammasome activation, inflammatory signaling and apoptosis
Summary
Nocardioform placentitis (NP) is defined as a focal mucoid placental inflammation in which the bacterial infection is limited to the chorionic surface of the ventralEl‐Sheikh Ali et al Vet Res (2021) 52:103 and insufficiency with large areas of the chorion that may be involved with the lesion [1]. Nocardioform placentitis (NP) is defined as a focal mucoid placental inflammation in which the bacterial infection is limited to the chorionic surface of the ventral. NP lesions may be seen in the CA in mares with normal neonates. The distribution of the placental lesion in NP is distinct from those of ascending bacterial placentitis with lesions of NP mainly distributed in the cranial-ventral portion of the placenta near the junction of the uterine horns and body [1]. The lesion is often sharply demarcated from the surrounding normal placenta, and the affected placenta is covered with a thick, tan mucoid material [1, 2]. The chorioallantois may demonstrate infiltration of neutrophils, lymphocytes, and macrophages with hyperplasia of the chorionic epithelium [1]. The chorionic villi are blunted and atrophied with lymphocytic infiltrates [1]
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