Transcriptomic analysis of equine placenta reveals key regulators and pathways involved in ascending placentitis

Hossam El-Sheikh Ali, Pouya Dini, Kirsten Scoggin, Shavahn Loux, Carleigh Fedorka, Yatta Boakari, Jamie Norris, Alejandro Esteller-Vico, Theodore Kalbfleisch, Barry Ball

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Improved understanding of the molecular mechanisms underlying ascending equine placentitis holds the potential for the development of new diagnostic tools and therapies to forestall placentitis-induced preterm labor. The current study characterized the equine placental transcriptome (chorioallantois [CA] and endometrium [EN]) during placentitis (placentitis group, n = 6) in comparison to gestationally-matched controls (control group, n = 6). Transcriptome analysis identified 2953 and 805 differentially expressed genes in CA and EN during placentitis, respectively. Upstream regulator analysis revealed the central role of toll-like receptors (TLRs) in triggering the inflammatory signaling, and consequent immune-cell chemotaxis. Placentitis was associated with the upregulation of matrix metalloproteinase (MMP1, MMP2, and MMP9) and apoptosis-related genes such as caspases (CASP3, CASP4, and CASP7) in CA. Also, placentitis was associated with downregulation of transcripts coding for proteins essential for placental steroidogenesis (SRD5A1 and AKR1C1), progestin signaling (PGRMC1 and PXR) angiogenesis (VEGFA, VEGFR2, and VEGFR3), and nutrient transport (GLUT12 and SLC1A4), as well as upregulation of hypoxia-related genes (HIF1A and EGLN3), which could explain placental insufficiency during placentitis. Placentitis was also associated with aberrant expression of several placenta-regulatory genes, such as PLAC8, PAPPA, LGALS1, ABCG2, GCM1, and TEPP, which could negatively affect placental functions. In conclusion, our findings revealed for the first time the key regulators and mechanisms underlying placental inflammation, separation, and insufficiency during equine placentitis, which might lead to the development of efficacious therapies or diagnostic aids by targeting the key molecular pathways.

Original languageEnglish
Pages (from-to)638-656
Number of pages19
JournalBiology of Reproduction
Volume104
Issue number3
DOIs
StatePublished - Mar 1 2021

Bibliographical note

Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Keywords

  • chorioallantois
  • endometrium
  • equine placentitis
  • placenta
  • pregnancy
  • transcriptome

ASJC Scopus subject areas

  • Reproductive Medicine

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