Presentation Title

Macrophage Morphology in Progesterone Regulation of Cervix Ripening at Term and with Preterm Birth

Faculty Mentor

Steven Yellon, Michael Kirby

Start Date

23-11-2019 8:45 AM

End Date

23-11-2019 9:30 AM

Location

96

Session

poster 2

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

A novel approach was used to elucidate the role of macrophage (Mφ) phenotype in the ripening murine cervix. Cervix ripening includes degradation of cross-linked extracellular collagen, reduced density of cell nuclei, and increased density of macrophagesPMID28395330. These biomarkers of inflammation are induced by progesterone receptor (PR) antagonists or blocked by PR agonists to regulate ripening and birthPMID27233754. In vitro, round (rM) and elongated (eM) Mφ shapes indicate inflammatory and anti-inflammatory activities, respectivelyPMID24101477. This in vivo study tested the hypothesis that PR modulators regulate Mφ shape to manage inflammatory drive of cervix ripening.

Sections derived from a previous study in which pregnant CD1 mice received on day 16 postbreeding the PR antagonist RU486 or were ovariectomized (Ovx) to induce preterm birth (PTB). Other Ovx mice were given the PR agonist R5020 to block PTB. Vehicle and sham-operated mice served as controls. The cervix was obtained prepartum 6h after treatment and the shape of F4/80-stained Mφs evaluated based on stringent morphological criteria.

Mφ shapes were rM, eM, or polymorphic (pM). All Mφ subtypes increased in vehicle controls by day 18 compared to previous days. 6h after RU486, all Mφ subtypes had increased vs vehicle controls on day 16.5, equal to that of vehicle day 18. Within 6h of Ovx only rM numbers increased. R5020 blocked these effects and reduced rM by day 18 vs Sham controls.

Increase in all Mφ shapes in the prepartum cervix of vehicle controls and earlier after RU486 suggests a balance of phenotypic pro- and anti-inflammatory activities remodels the cervix before term and PTB. Progesterone withdrawal by Ovx and R5020 suppression of remodeling and PTB may be mediated solely by the rM subtype. Murine models for Mφ polarization have the potential to identify biomarkers to diagnose risk for PTB and provide immunotherapeutic approaches to modulate cervix ripening.

This document is currently not available here.

Share

COinS
 
Nov 23rd, 8:45 AM Nov 23rd, 9:30 AM

Macrophage Morphology in Progesterone Regulation of Cervix Ripening at Term and with Preterm Birth

96

A novel approach was used to elucidate the role of macrophage (Mφ) phenotype in the ripening murine cervix. Cervix ripening includes degradation of cross-linked extracellular collagen, reduced density of cell nuclei, and increased density of macrophagesPMID28395330. These biomarkers of inflammation are induced by progesterone receptor (PR) antagonists or blocked by PR agonists to regulate ripening and birthPMID27233754. In vitro, round (rM) and elongated (eM) Mφ shapes indicate inflammatory and anti-inflammatory activities, respectivelyPMID24101477. This in vivo study tested the hypothesis that PR modulators regulate Mφ shape to manage inflammatory drive of cervix ripening.

Sections derived from a previous study in which pregnant CD1 mice received on day 16 postbreeding the PR antagonist RU486 or were ovariectomized (Ovx) to induce preterm birth (PTB). Other Ovx mice were given the PR agonist R5020 to block PTB. Vehicle and sham-operated mice served as controls. The cervix was obtained prepartum 6h after treatment and the shape of F4/80-stained Mφs evaluated based on stringent morphological criteria.

Mφ shapes were rM, eM, or polymorphic (pM). All Mφ subtypes increased in vehicle controls by day 18 compared to previous days. 6h after RU486, all Mφ subtypes had increased vs vehicle controls on day 16.5, equal to that of vehicle day 18. Within 6h of Ovx only rM numbers increased. R5020 blocked these effects and reduced rM by day 18 vs Sham controls.

Increase in all Mφ shapes in the prepartum cervix of vehicle controls and earlier after RU486 suggests a balance of phenotypic pro- and anti-inflammatory activities remodels the cervix before term and PTB. Progesterone withdrawal by Ovx and R5020 suppression of remodeling and PTB may be mediated solely by the rM subtype. Murine models for Mφ polarization have the potential to identify biomarkers to diagnose risk for PTB and provide immunotherapeutic approaches to modulate cervix ripening.