Racial differences in the fetal membrane inflammatory response: A possible explanation for the ethnic disparity in prematurity

Abstract

RACIAL DIFFERENCES IN THE FETAL MEMBRANE INFLAMMATORY RESPONSE: A POSSIBLE EXPLANATION FOR THE ETHNIC DISPARITY IN PREMATURITY STEPHEN FORTUNATO, SALVATORE LOMBARDI, RAMKUMAR MENON, The Perinatal Research Center, Maternal-Fetal Medicine, Nashville, Tennessee, Maternal-Fetal Medicine, Nashville, Tennessee, Perinatal Research Center, Nashville, Tennessee OBJECTIVE: The prematurity rate is higher in African-Americans (AA) compared to Caucasians (C) (18% vs. 9%). Spontaneous preterm delivery (PTD) has been shown to be a host inflammatory response disease. Racial differences in placental membrane inflammatory gene expression patterns (cytokines, MMPs and caspases) were examined in this report. STUDY DESIGN: Fetal membranes collected from AA and C women from cesareans at term were maintained in an organ explant system and stimulated with of endotoxin. mRNAs were subjected to microarray analysis with C derived samples labeled with Cy5 dye (wavelength 635 nm) and AA samples labeled with Cy3 dye (wavelength 538 nm). The ratio of median intensities for each wavelength was calculated and data was generated using GenePix 4.0 software. ELISA measured the culture media concentrations of many of the interested inflammatory agents. RESULTS: Microarray data is shown in Table. Concentrations of IL-1 and MMP9 were higher in media derived from AA whereas IL-6 and TNF concentrations were higher in C and no changes were seen IL-8 and TIMP1 concentrations between the two groups after stimulation. CONCLUSION: The list of upregulated genes that are involved in proinflammatory response is greater AA derived membranes compared to C. Inflammatory cytokines, MMPs and both initiator and effecter caspases are upregulated in AA but not in C. AA show a pro inflammatory shift with not much change in the inhibitor/antagonists expression. In contrast there is an up regulation of inhibitors in C. This indicates a pro-inflammatory response in AA and a more balanced response in C. This disparity in membrane response to infection may be a factor for the high rate of PTD in AA.