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Placental ischemia induces changes in gene expression in chorionic tissue

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Abstract

Preeclampsia is a serious and common hypertensive complication of pregnancy, affecting ~5 to 8 % of pregnancies. The underlying cause of preeclampsia is believed to be placental ischemia, which causes secretion of pathogenic factors into the maternal circulation. While a number of these factors have been identified, it is likely that others remain to be elucidated. Here, we have utilized a relevant preclinical rodent model of placental ischemia-induced hypertension, the reduced uterine perfusion pressure (RUPP) model, to determine the effect of chronic placental ischemia on the underlying chorionic tissue and placental villi. Tissue from control and RUPP rats were isolated on gestational day 19 and mRNA from these tissues was subjected to microarray analysis to determine differential gene expression. At a statistical cutoff of p < 0.05, some 2,557 genes were differentially regulated between the two groups. Interestingly, only a small subset (22) of these genes exhibited changes of greater than 50 % versus control, a large proportion of which were subsequently confirmed using qRT-PCR analysis. Network analysis indicated a strong effect on inflammatory pathways, including those involving NF-κB and inflammatory cytokines. Of the most differentially expressed genes, the predominant gene classes were extracellular remodeling proteins, pro-inflammatory proteins, and a coordinated upregulation of the prolactin genes. The functional implications of these novel factors are discussed.

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Acknowledgments

Support for this research was provided by NIH Grants K99HL116774 (EMG), R01Hl108618, and P01HL51971 (JPG). The work performed through the UMMC Molecular and Genomics Facility is supported, in part, by funds from the National Institute of General Medical Sciences of the National Institutes of Health, including Mississippi INBRE (P20GM103476), Center for Psychiatric Neurosciences (CPN)-COBRE (P30GM103328), and Obesity, Cardiorenal and Metabolic Diseases COBRE (P20GM104357).

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  1. Departments of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS, 39216, USA

    Eric M. George & Joey P. Granger

  2. Departments of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS, 39216, USA

    Michael R. Garrett

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  1. Eric M. George
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Correspondence to Eric M. George.

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George, E.M., Garrett, M.R. & Granger, J.P. Placental ischemia induces changes in gene expression in chorionic tissue. Mamm Genome 25, 253–261 (2014). https://doi.org/10.1007/s00335-014-9505-3

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