Progesterone improves perinatal neuromotor outcomes in a mouse model of intrauterine inflammation via immunomodulation of the placenta

Christopher Novak, Maide Ozen, Michael Mclane, Sadiq Alqutub, Ji Yeon Lee, Jun Lei, Irina Burd

Research output: Contribution to journalArticle

Abstract

To assess the fetal neuroprotective potential of progesterone using a well-validated mouse model of lipopolysaccharide (LPS)-induced intrauterine inflammation (IUI). Embryonic day 17 pregnant mouse dams (n = 69) were randomly allocated to receive 17-hydroxyprogesterone caproate (17-OHPC), micronized progesterone (MP), or vehicle 1 hour prior to intrauterine injection of phosphate-buffered saline (PBS) or LPS. After 6 hours, mice were killed for the collection of placentas and fetal brains, or pregnancy continued for the evaluation of preterm birth (PTB) and offspring neuromotor function. Placentas and fetal brains were analyzed by mini-mRNA array for 96 immune markers with individual confirmatory qPCR. Progesterone pre-treatment before LPS-induced IUI improved neuromotor tests in offspring at PND5 compared to no pre-treatment (P < .05). In placentas, 17-OHPC, but not MP, significantly reduced CXCL9 (P < .05) with a trend toward a lower level of CXCL10. In fetal brains, 17-OHPC significantly reduced CXCL9 compared to no pre-treatment (P < .05) and IL-1β compared to pre-treatment with MP (P < .01). Progesterone pre-treatment prior to LPS-induced IUI improved offspring neuromotor outcomes. 17-OHPC, but not MP, resulted in greater immunomodulation of T cell-mediated immunity in placenta and fetal brain, suggesting a possible mechanism for the observed neuroprotective effects.

Original languageEnglish (US)
JournalAmerican Journal of Reproductive Immunology
DOIs
StateAccepted/In press - Jan 1 2018

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Immunomodulation
Placenta
Progesterone
Inflammation
Lipopolysaccharides
Brain
17-alpha-Hydroxyprogesterone
Therapeutics
Premature Birth
Neuroprotective Agents
Interleukin-1
Cellular Immunity
Biomarkers
Phosphates
T-Lymphocytes
Pregnancy
Messenger RNA
Injections

Keywords

  • 17-hydroxyprogesterone caproate
  • Fetal neuroprotection
  • Intrauterine inflammation
  • Preterm birth
  • Progesterone

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

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title = "Progesterone improves perinatal neuromotor outcomes in a mouse model of intrauterine inflammation via immunomodulation of the placenta",
abstract = "To assess the fetal neuroprotective potential of progesterone using a well-validated mouse model of lipopolysaccharide (LPS)-induced intrauterine inflammation (IUI). Embryonic day 17 pregnant mouse dams (n = 69) were randomly allocated to receive 17-hydroxyprogesterone caproate (17-OHPC), micronized progesterone (MP), or vehicle 1 hour prior to intrauterine injection of phosphate-buffered saline (PBS) or LPS. After 6 hours, mice were killed for the collection of placentas and fetal brains, or pregnancy continued for the evaluation of preterm birth (PTB) and offspring neuromotor function. Placentas and fetal brains were analyzed by mini-mRNA array for 96 immune markers with individual confirmatory qPCR. Progesterone pre-treatment before LPS-induced IUI improved neuromotor tests in offspring at PND5 compared to no pre-treatment (P < .05). In placentas, 17-OHPC, but not MP, significantly reduced CXCL9 (P < .05) with a trend toward a lower level of CXCL10. In fetal brains, 17-OHPC significantly reduced CXCL9 compared to no pre-treatment (P < .05) and IL-1β compared to pre-treatment with MP (P < .01). Progesterone pre-treatment prior to LPS-induced IUI improved offspring neuromotor outcomes. 17-OHPC, but not MP, resulted in greater immunomodulation of T cell-mediated immunity in placenta and fetal brain, suggesting a possible mechanism for the observed neuroprotective effects.",
keywords = "17-hydroxyprogesterone caproate, Fetal neuroprotection, Intrauterine inflammation, Preterm birth, Progesterone",
author = "Christopher Novak and Maide Ozen and Michael Mclane and Sadiq Alqutub and Lee, {Ji Yeon} and Jun Lei and Irina Burd",
year = "2018",
month = "1",
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doi = "10.1111/aji.12842",
language = "English (US)",
journal = "American Journal of Reproductive Immunology and Microbiology",
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T1 - Progesterone improves perinatal neuromotor outcomes in a mouse model of intrauterine inflammation via immunomodulation of the placenta

AU - Novak, Christopher

AU - Ozen, Maide

AU - Mclane, Michael

AU - Alqutub, Sadiq

AU - Lee, Ji Yeon

AU - Lei, Jun

AU - Burd, Irina

PY - 2018/1/1

Y1 - 2018/1/1

N2 - To assess the fetal neuroprotective potential of progesterone using a well-validated mouse model of lipopolysaccharide (LPS)-induced intrauterine inflammation (IUI). Embryonic day 17 pregnant mouse dams (n = 69) were randomly allocated to receive 17-hydroxyprogesterone caproate (17-OHPC), micronized progesterone (MP), or vehicle 1 hour prior to intrauterine injection of phosphate-buffered saline (PBS) or LPS. After 6 hours, mice were killed for the collection of placentas and fetal brains, or pregnancy continued for the evaluation of preterm birth (PTB) and offspring neuromotor function. Placentas and fetal brains were analyzed by mini-mRNA array for 96 immune markers with individual confirmatory qPCR. Progesterone pre-treatment before LPS-induced IUI improved neuromotor tests in offspring at PND5 compared to no pre-treatment (P < .05). In placentas, 17-OHPC, but not MP, significantly reduced CXCL9 (P < .05) with a trend toward a lower level of CXCL10. In fetal brains, 17-OHPC significantly reduced CXCL9 compared to no pre-treatment (P < .05) and IL-1β compared to pre-treatment with MP (P < .01). Progesterone pre-treatment prior to LPS-induced IUI improved offspring neuromotor outcomes. 17-OHPC, but not MP, resulted in greater immunomodulation of T cell-mediated immunity in placenta and fetal brain, suggesting a possible mechanism for the observed neuroprotective effects.

AB - To assess the fetal neuroprotective potential of progesterone using a well-validated mouse model of lipopolysaccharide (LPS)-induced intrauterine inflammation (IUI). Embryonic day 17 pregnant mouse dams (n = 69) were randomly allocated to receive 17-hydroxyprogesterone caproate (17-OHPC), micronized progesterone (MP), or vehicle 1 hour prior to intrauterine injection of phosphate-buffered saline (PBS) or LPS. After 6 hours, mice were killed for the collection of placentas and fetal brains, or pregnancy continued for the evaluation of preterm birth (PTB) and offspring neuromotor function. Placentas and fetal brains were analyzed by mini-mRNA array for 96 immune markers with individual confirmatory qPCR. Progesterone pre-treatment before LPS-induced IUI improved neuromotor tests in offspring at PND5 compared to no pre-treatment (P < .05). In placentas, 17-OHPC, but not MP, significantly reduced CXCL9 (P < .05) with a trend toward a lower level of CXCL10. In fetal brains, 17-OHPC significantly reduced CXCL9 compared to no pre-treatment (P < .05) and IL-1β compared to pre-treatment with MP (P < .01). Progesterone pre-treatment prior to LPS-induced IUI improved offspring neuromotor outcomes. 17-OHPC, but not MP, resulted in greater immunomodulation of T cell-mediated immunity in placenta and fetal brain, suggesting a possible mechanism for the observed neuroprotective effects.

KW - 17-hydroxyprogesterone caproate

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KW - Preterm birth

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