title: Macrophage gene expression associated with remodeling of the prepartum rat cervix: microarray and pathway analyses.
abstract: As the critical gatekeeper for birth, prepartum remodeling of the cervix is associated with increased resident macrophages (Mφ), proinflammatory processes, and extracellular matrix degradation. This study tested the hypothesis that expression of genes unique to Mφs characterizes the prepartum from unremodeled nonpregnant cervix. Perfused cervix from prepartum day 21 postbreeding (D21) or nonpregnant (NP) rats, with or without Mφs, had RNA extracted and whole genome microarray analysis performed. By subtractive analyses, expression of 194 and 120 genes related to Mφs in the cervix from D21 rats were increased and decreased, respectively. In both D21 and NP groups, 158 and 57 Mφ genes were also more or less up- or down-regulated, respectively. Mφ gene expression patterns were most strongly correlated within groups and in 5 major clustering patterns. In the cervix from D21 rats, functional categories and canonical pathways of increased expression by Mφ gene related to extracellular matrix, cell proliferation, differentiation, as well as cell signaling. Pathways were characteristic of inflammation and wound healing, e.g., CD163, CD206, and CCR2. Signatures of only inflammation pathways, e.g., CSF1R, EMR1, and MMP12 were common to both D21 and NP groups. Thus, a novel and complex balance of Mφ genes and clusters differentiated the degraded extracellular matrix and cellular genomic activities in the cervix before birth from the unremodeled state. Predicted Mφ activities, pathways, and networks raise the possibility that expression patterns of specific genes characterize and promote prepartum remodeling of the cervix for parturition at term and with preterm labor.
authors: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America.
authors: Abigail E
authors: AE
authors: Dobyns
authors: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America; Division of Physiology, Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America.
authors: Ravi
authors: R
authors: Goyal
authors: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America.
authors: Lauren Grisham
authors: LG
authors: Carpenter
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, Edinburgh, EH25 9RG, United Kingdom.
authors: Tom C
authors: TC
authors: Freeman
authors: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America; Departments of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America; Division of Physiology, Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America.
authors: Lawrence D
authors: LD
authors: Longo
authors: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America; Departments of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America; Division of Physiology, Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, 92350, United States of America.
authors: Steven M
authors: SM
authors: Yellon
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000378:metabolism*; D016000:Cluster Analysis; D015536:Down-Regulation; D005260:Female; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics