Equine placentitis is associated with a downregulation in myometrial progestin signaling†

Hossam El-Sheikh Ali, Erin L. Legacki, Shavahn C. Loux, Alejandro Esteller-Vico, Pouya Dini, Kirsten E. Scoggin, Alan J Conley, Scott D Stanley, Barry A. Ball

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The current study aimed to elucidate the mechanisms underlying myometrial activation during equine placentitis related to progestogens and the progesterone receptor signaling pathways. Placentitis was induced via intracervical inoculation with Streptococcus equi ssp zooepidemicus in mares at approximately 290 days of gestation (placentitis group; n = 6) with uninoculated gestationally matched mares as controls (n = 4). Mares in the placentitis and control groups were euthanized, and myometrial samples were collected from two regions: region 1-parallel to active placentitis lesion with placental separation in placentitis group (P1) or caudal pole of the placenta in control group (C1); and region 2-parallel to apparently normal placenta without separation in placentitis group (P2) or uterine body in control group (C2). In the current study, SRD5A1 and AKR1C23, which encode for the key P4 metabolizing enzymes, were downregulated in P1 in comparison to C1, C2, and P2, and this was associated with a decline (P < 0.05) in 5αDHP, allopregnanolone (3αDHP), and 20αDHP in P1 in comparison to C1. Further, myometrial expression of PR was downregulated (P < 0.05) in P1 in comparison to C1 and P2, and this was associated with activation of the inflammatory cascade as reflected by significant upregulation of IL-1β and IL-8 in P1 in comparison to C1, C2, and P2, and supported by increased tissue leukocytes in P1 in comparison to C1. In conclusion, equine placentitis is associated with a localized withdrawal of progestins and a downregulation of the PR in the myometrium concomitant with upregulation of inflammatory cytokines and subsequent myometrial activation.

Original languageEnglish (US)
Pages (from-to)162-176
Number of pages15
JournalBiology of reproduction
Volume101
Issue number1
DOIs
StatePublished - Jul 1 2019

Fingerprint

Progestins
Horses
Down-Regulation
Control Groups
Placenta
Up-Regulation
Streptococcus equi
Pregnanolone
Myometrium
Progesterone Receptors
Interleukin-8
Interleukin-1
Leukocytes
Cytokines
Pregnancy
Enzymes

Keywords

  • equine placentitis
  • myometrium
  • pregnancy
  • progesterone receptor (PR)
  • progestin

ASJC Scopus subject areas

  • Cell Biology

Cite this

El-Sheikh Ali, H., Legacki, E. L., Loux, S. C., Esteller-Vico, A., Dini, P., Scoggin, K. E., ... Ball, B. A. (2019). Equine placentitis is associated with a downregulation in myometrial progestin signaling†. Biology of reproduction, 101(1), 162-176. https://doi.org/10.1093/biolre/ioz059

Equine placentitis is associated with a downregulation in myometrial progestin signaling†. / El-Sheikh Ali, Hossam; Legacki, Erin L.; Loux, Shavahn C.; Esteller-Vico, Alejandro; Dini, Pouya; Scoggin, Kirsten E.; Conley, Alan J; Stanley, Scott D; Ball, Barry A.

In: Biology of reproduction, Vol. 101, No. 1, 01.07.2019, p. 162-176.

Research output: Contribution to journalArticle

El-Sheikh Ali, H, Legacki, EL, Loux, SC, Esteller-Vico, A, Dini, P, Scoggin, KE, Conley, AJ, Stanley, SD & Ball, BA 2019, 'Equine placentitis is associated with a downregulation in myometrial progestin signaling†', Biology of reproduction, vol. 101, no. 1, pp. 162-176. https://doi.org/10.1093/biolre/ioz059
El-Sheikh Ali H, Legacki EL, Loux SC, Esteller-Vico A, Dini P, Scoggin KE et al. Equine placentitis is associated with a downregulation in myometrial progestin signaling†. Biology of reproduction. 2019 Jul 1;101(1):162-176. https://doi.org/10.1093/biolre/ioz059
El-Sheikh Ali, Hossam ; Legacki, Erin L. ; Loux, Shavahn C. ; Esteller-Vico, Alejandro ; Dini, Pouya ; Scoggin, Kirsten E. ; Conley, Alan J ; Stanley, Scott D ; Ball, Barry A. / Equine placentitis is associated with a downregulation in myometrial progestin signaling†. In: Biology of reproduction. 2019 ; Vol. 101, No. 1. pp. 162-176.
@article{e1bcba8937314cebb8adf06af1dc8a99,
title = "Equine placentitis is associated with a downregulation in myometrial progestin signaling†",
abstract = "The current study aimed to elucidate the mechanisms underlying myometrial activation during equine placentitis related to progestogens and the progesterone receptor signaling pathways. Placentitis was induced via intracervical inoculation with Streptococcus equi ssp zooepidemicus in mares at approximately 290 days of gestation (placentitis group; n = 6) with uninoculated gestationally matched mares as controls (n = 4). Mares in the placentitis and control groups were euthanized, and myometrial samples were collected from two regions: region 1-parallel to active placentitis lesion with placental separation in placentitis group (P1) or caudal pole of the placenta in control group (C1); and region 2-parallel to apparently normal placenta without separation in placentitis group (P2) or uterine body in control group (C2). In the current study, SRD5A1 and AKR1C23, which encode for the key P4 metabolizing enzymes, were downregulated in P1 in comparison to C1, C2, and P2, and this was associated with a decline (P < 0.05) in 5αDHP, allopregnanolone (3αDHP), and 20αDHP in P1 in comparison to C1. Further, myometrial expression of PR was downregulated (P < 0.05) in P1 in comparison to C1 and P2, and this was associated with activation of the inflammatory cascade as reflected by significant upregulation of IL-1β and IL-8 in P1 in comparison to C1, C2, and P2, and supported by increased tissue leukocytes in P1 in comparison to C1. In conclusion, equine placentitis is associated with a localized withdrawal of progestins and a downregulation of the PR in the myometrium concomitant with upregulation of inflammatory cytokines and subsequent myometrial activation.",
keywords = "equine placentitis, myometrium, pregnancy, progesterone receptor (PR), progestin",
author = "{El-Sheikh Ali}, Hossam and Legacki, {Erin L.} and Loux, {Shavahn C.} and Alejandro Esteller-Vico and Pouya Dini and Scoggin, {Kirsten E.} and Conley, {Alan J} and Stanley, {Scott D} and Ball, {Barry A.}",
year = "2019",
month = "7",
day = "1",
doi = "10.1093/biolre/ioz059",
language = "English (US)",
volume = "101",
pages = "162--176",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "1",

}

TY - JOUR

T1 - Equine placentitis is associated with a downregulation in myometrial progestin signaling†

AU - El-Sheikh Ali, Hossam

AU - Legacki, Erin L.

AU - Loux, Shavahn C.

AU - Esteller-Vico, Alejandro

AU - Dini, Pouya

AU - Scoggin, Kirsten E.

AU - Conley, Alan J

AU - Stanley, Scott D

AU - Ball, Barry A.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - The current study aimed to elucidate the mechanisms underlying myometrial activation during equine placentitis related to progestogens and the progesterone receptor signaling pathways. Placentitis was induced via intracervical inoculation with Streptococcus equi ssp zooepidemicus in mares at approximately 290 days of gestation (placentitis group; n = 6) with uninoculated gestationally matched mares as controls (n = 4). Mares in the placentitis and control groups were euthanized, and myometrial samples were collected from two regions: region 1-parallel to active placentitis lesion with placental separation in placentitis group (P1) or caudal pole of the placenta in control group (C1); and region 2-parallel to apparently normal placenta without separation in placentitis group (P2) or uterine body in control group (C2). In the current study, SRD5A1 and AKR1C23, which encode for the key P4 metabolizing enzymes, were downregulated in P1 in comparison to C1, C2, and P2, and this was associated with a decline (P < 0.05) in 5αDHP, allopregnanolone (3αDHP), and 20αDHP in P1 in comparison to C1. Further, myometrial expression of PR was downregulated (P < 0.05) in P1 in comparison to C1 and P2, and this was associated with activation of the inflammatory cascade as reflected by significant upregulation of IL-1β and IL-8 in P1 in comparison to C1, C2, and P2, and supported by increased tissue leukocytes in P1 in comparison to C1. In conclusion, equine placentitis is associated with a localized withdrawal of progestins and a downregulation of the PR in the myometrium concomitant with upregulation of inflammatory cytokines and subsequent myometrial activation.

AB - The current study aimed to elucidate the mechanisms underlying myometrial activation during equine placentitis related to progestogens and the progesterone receptor signaling pathways. Placentitis was induced via intracervical inoculation with Streptococcus equi ssp zooepidemicus in mares at approximately 290 days of gestation (placentitis group; n = 6) with uninoculated gestationally matched mares as controls (n = 4). Mares in the placentitis and control groups were euthanized, and myometrial samples were collected from two regions: region 1-parallel to active placentitis lesion with placental separation in placentitis group (P1) or caudal pole of the placenta in control group (C1); and region 2-parallel to apparently normal placenta without separation in placentitis group (P2) or uterine body in control group (C2). In the current study, SRD5A1 and AKR1C23, which encode for the key P4 metabolizing enzymes, were downregulated in P1 in comparison to C1, C2, and P2, and this was associated with a decline (P < 0.05) in 5αDHP, allopregnanolone (3αDHP), and 20αDHP in P1 in comparison to C1. Further, myometrial expression of PR was downregulated (P < 0.05) in P1 in comparison to C1 and P2, and this was associated with activation of the inflammatory cascade as reflected by significant upregulation of IL-1β and IL-8 in P1 in comparison to C1, C2, and P2, and supported by increased tissue leukocytes in P1 in comparison to C1. In conclusion, equine placentitis is associated with a localized withdrawal of progestins and a downregulation of the PR in the myometrium concomitant with upregulation of inflammatory cytokines and subsequent myometrial activation.

KW - equine placentitis

KW - myometrium

KW - pregnancy

KW - progesterone receptor (PR)

KW - progestin

UR - http://www.scopus.com/inward/record.url?scp=85069294550&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069294550&partnerID=8YFLogxK

U2 - 10.1093/biolre/ioz059

DO - 10.1093/biolre/ioz059

M3 - Article

C2 - 31107530

AN - SCOPUS:85069294550

VL - 101

SP - 162

EP - 176

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 1

ER -