Transcriptomic analysis reveals the key regulators and molecular mechanisms underlying myometrial activation during equine placentitis

H. El-Sheikh Ali, Y. L. Boakari, S. C. Loux, P. DIni, K. E. Scoggin, A. Esteller-Vico, T. Kalbfleisch, B. A. Ball

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The key event in placentitis-induced preterm labor is myometrial activation with the subsequent initiation of labor. However, the molecular mechanisms underlying myometrial activation are not fully understood in the mares. Therefore, the equine myometrial transcriptome was characterized during placentitis (290.0 ± 1.52 days of GA, n = 5) and the prepartum period (330 days of GA, n = 3) in comparison to normal pregnant mares (289.8 ± 2.18 days of GA, n = 4). Transcriptome analysis identified 596 and 290 DEGs in the myometrium during placentitis and the prepartum period, respectively, with 138 DEGs in common. The placentitis DEGs included eight genes (MMP1, MMP8, S100A9, S100A8, PI3, APOBEC3Z1B, RETN, and CXCL2) that are exclusively expressed in the inflamed myometrium. Pathway analysis elucidated that inflammatory signaling, Toll-like receptor signaling, and apoptosis pathways dominate myometrial activation during placentitis. The prepartum myometrium was associated with overexpression of inflammatory signaling, oxidative stress, and 5-hydroxytryptamine degradation. Gene ontology enrichment analysis identified several chemoattractant factors in the myometrium during placentitis and prepartum period, including CCL2, CXCL1, CXCL3, and CXCL6 in common. Upstream regulator analysis revealed 19 potential upstream regulators in placentitis dataset including transcription regulators (E2F1, FOXM1, HIF1A, JUNB, NFKB1A, and STAT1), transmembrane receptors (FAS, ICAM1, SELP, TLR2, and TYROBP), growth factors (HGF and TGFB3), enzymes (PTGS2 and PRKCP), and others (S100A8, S100A9, CD44, and C5AR1). Additionally, three upstream regulators (STAT3, EGR1, and F2R) were identified in the prepartum dataset. These findings revealed the key regulators and pathways underlying myometrial activation during placentitis, which aid in understanding the disease and facilitate the development of efficacious therapies.

Original languageEnglish
Pages (from-to)1306-1325
Number of pages20
JournalBiology of Reproduction
Volume102
Issue number6
DOIs
StatePublished - May 26 2020

Bibliographical note

Funding Information:
This research was supported by the Albert G. Clay Endowment, the Clay Fellowship, and the Mellon postdoctoral scholarship of the University of Kentucky. H. El-Sheikh Ali was supported by The U.S.-Egypt Science and Technology Joint Fund (STDF: #USC17:140).

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

  • equine placentitis
  • myometrium
  • pregnancy
  • prepartum period
  • preterm labor
  • transcriptome

ASJC Scopus subject areas

  • Reproductive Medicine

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