Abstract

Macrophage-derived factors have been implicated in the etiology of preterm labor but little is known about trafficking of this immune cell into the uterus or its regulation of uterine contractility in mice. Enhanced number and activation of macrophages was hypothesized to precede parturition. Studies characterized contractile activity and the distribution of macrophages in the uterus of C3/HeN mice before and after term (=day 19). Contractile activity by uterine strips on days 15 and 18 of pregnancy, the day of delivery, and 1 day postpartum indicate that an endogenous oscillator sustains high frequency contractions. Modest acceleration of the pacemaker occurred before birth but basal contraction amplitude increased 5-fold between the day before and the day of birth. Thus, a dramatic increase in amplitude characterized the transition to powerful synchronous contractions during parturition. Tissue strips were then sectioned and stained with either a pan-macrophage (BM8) or an anti-CD54 antibody to enumerate macrophages and assess activation. In endometrium, macrophage numbers decreased on the day before delivery from day 15 levels, but increased postpartum to regain peak levels. Data suggest macrophage trafficking out of the endometrium before term. Macrophage numbers in endometrium were inversely related to those in cervix, which peaked on the day before birth. In myometrium, macrophage numbers were elevated before and after birth compared to nonpregnant controls. Laser scanning cytometry enumerated CD54+ cells and their cell cycle. Data suggest that enhanced numbers of non-terminally differentiated macrophages were activated in the uterus 4 days before term but declined by 1 day before birth. The hypothesis that macrophages may regulate uterine contractility was then tested. Administration of lipopolysaccharide (LPS) to uterine strips in vitro enhanced contractility. This effect, presumably to activate resident macrophages, was blocked by anti-inflammatory treatments. This is an indication that macrophage-derived prostaglandins and cytokines may regulate uterine contractile activity. These findings support the hypothesis that uterine macrophages participate in the process of parturition. Preterm macropbage emigration from the endometrium may eliminate a cellular mechanism for quiescence in favor of myometrial macrophage produced factors that enhance uterine contractility and promote the onset of labor.

LLU Discipline

Physiology

Department

Physiology

School

Graduate School

First Advisor

Steven M. Yellon

Second Advisor

Edwin L. Cooper

Third Advisor

Charles A. Ducsay

Fourth Advisor

Lawrence D. Longo

Fifth Advisor

Sandra L. Nehlsen-Cannarella

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1999

Date (Title Page)

6-1999

Language

English

Library of Congress/MESH Subject Headings

Labor -- immunology; Labor -- physiology.

Type

Dissertation

Page Count

vii; 147

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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