Cellular remodeling in the prepartum rat cervix: microarray and pathway analyses of macrophage-related gene expression

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 554-573-Ovarian & Uterine Function I
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-567
Steven M Yellon*1, Ravi Goyal2, Lauren Grisham-Carpenter2, Allison Oshiro2 and Lawrence D Longo2
1Loma Linda Univ Sch of Med, Loma Linda, CA, 2Loma Linda Univ Sch Med
Remodeling of the uterine cervix is a critical gatekeeper for birth. Near term, evidence suggests that infiltration by myeloid immune cell along with local actions by proinflammatory mediators and proteolytic enzymes are associated with cervical remodeling. The present study used microarray analysis to test the hypothesis that macrophage-related gene expression and pathways are regulated differentially in the cervix of prepartum compared to nonpregnant rats.  The excised cervix from pregnant rats on day 21 postbreeding (D21, day before birth) and from nonpregnant rats (NP) were flash frozen after dispersal or after a magnetic bead separation procedure to remove macrophages. Samples were sent to GenUs Biosystems (Northbrook, IL) for RNA extraction and rat genome microarray analysis using an Agilent RNA6000 Nano Lab Chip.  Data (average of 3 individuals/group) were analyzed with Ingenuity Pathway Analysis software (Redwood City, CA). In cervices from D21 vs NP rats, expression of 652 and 330 genes were up regulated or down regulated, respectively (p<0.05, >2-fold).  The cervix from D21 rats had 351 up regulated and 299 down regulated genes exclusively related to macrophages. Up regulated macrophage-related genes were most commonly part of functions linked to antigen presenting cells (T lymphocyte activation, immune responses, phagocyte actions) and innate responses to toxins (endotoxin responses, septic shock). By contrast, far fewer functions associated with macrophage-related genes were down regulated (organismal death, parasitic infection, fibroblast colony formation).  Unique canonical pathways of gene expression related to macrophage included cellular signaling by IL-17A, ERK5, and p38 MAPK. These data are the first to indicate that differential gene expression in the prepartum cervix of the rat are related to macrophages and are part of functional activities known to regulate extracellular matrix collagen, movement of cells, and specific inflammatory chemokines. Therefore with the present approach, molecules in functional and canonical pathways were found that may contribute to mechanism for remodeling the uterine cervix in preparation for birth. Whether gene expression studies can identify sentinel molecules to evaluate the progress of remodeling or are useful for a therapeutic strategy that ensure the timely ripening of the cervix remains to be determined.

Nothing to Disclose: SMY, RG, LG, AO, LDL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH HD054931