GPR18 Distribution and Expression in Human Placenta

Abstract

BackgroundOptimally functioning inflammation resolution systems during pregnancy are essential in regulating a series of complex processes that could degenerate into persistent inflammation and result in poor maternal‐child outcomes. Infants developing in a pro‐inflammatory intrauterine environment are at significantly higher risk for severe complications than infants born without pregnancy inflammatory risk factors.Specialized pro‐resolving lipid mediators (SPM) are chemical structures derived from polyunsaturated fatty acids. Resolution of acute inflammation is an active process regulated by SPM, including resolvin D2 (RvD2), a potent docosahexaenoic acid‐derived resolution‐phase mediator, which activates a cell surface G protein–coupled receptor, GPR18/RvD2.Preliminary data from our group indicate that the SPM RvD2 is significantly increased in maternal plasma taken at the time of delivery compared to cord blood plasma (3,450 vs. 689 pg/mL for maternal vs. cord, respectively, p<0.001), with further increases in the maternal plasma of cases with adverse maternal‐fetal outcomes, including NICU admission. Based on this data, we hypothesize that the placenta is a target site of action of SPM during perinatal growth and development. We identified the expression of the RvD2 receptor, GPR18 by immunostain on decidual cells, smooth muscle of the maternal and fetal arteries and syncytiotrophoblast, cytotrophoblast and macrophages of chorionic villi. Since the decidual cells showed significant expression of GRP18 therefore, the objective of this study was to analyze and categorize the different levels of staining intensity in this cell type.MethodsTen cross‐sections of placental tissues containing both maternal and fetal sides were stained for SPM‐binding receptor, GPR18 immunostaining, and digitized at 40× magnification using VENTANA iScan HT scanner. Our novel approach including Definiens Tissue Studio® software was used to quantify the cellular analyses of decidual cells in these digitized images that quantify low, medium, and high expressions for GPR18.ResultsThe majority of decidual cells showed medium or high GPR18 membranous and cytoplasmic expression (Figure 1). 20% of decidua cells had no areas of low expression. Seven out of ten samples had areas of medium expression that were greater than 50%. Areas of low expression ranged from 0–31%, while areas of medium expression ranged from 11–81%, and high expression ranged from 5–75%.ConclusionsThe decidual cells of the placenta have medium/high membranous and cytoplasmic expression of GPR18. SPM may be an important component of the inflammation physiology in the placental tissue. The expression of GPR18 may play a protective role in pregnancy and perinatal disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.