HLA gene expression is altered in whole blood and placenta from women who later developed preeclampsia.

Preeclampsia is a multisystem disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 wk of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. We studied gene expression profiles using Illumina microarray in blood and validated changes in gene expression in whole blood and placenta tissue by qPCR. We found a transcriptional profile differentiating cases from controls; 336 genes were significantly dysregulated in blood from women who developed preeclampsia. Functional annotation of microarray results indicated that most of the genes found to be dysregulated were involved in inflammatory pathways. While general trends were preserved, only HLA-A was validated in whole blood samples from cases using qPCR (2.30- ± 0.9-fold change) whereas in placental tissue HLA-DRB1 expression was found to be significantly increased in samples from women with preeclampsia (5.88- ± 2.24-fold change). We have identified that HLA-A is upregulated in the circulation of women who went on to develop preeclampsia. In placenta of women with preeclampsia we identified that HLA-DRB1 is upregulated. Our data provide further evidence for involvement of the HLA gene family in the pathogenesis of preeclampsia.

Differential expression of microRNA-206 and its target genes in preeclampsia.

OBJECTIVES: Preeclampsia is a multisystem disease that significantly contributes to maternal and foetal morbidity and mortality. In this study, we used a nonbiased microarray approach to identify novel circulating miRNAs in maternal plasma that may be associated with preeclampsia. METHODS: Plasma samples were obtained at 16 and 28 weeks of gestation from 18 women who later developed preeclampsia (cases) and 18 matched women with normotensive pregnancies (controls). We studied miRNA expression profiles in plasma and subsequently confirmed miRNA and target gene expression in placenta samples. Placental samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. RESULTS: From the microarray, we identified one miRNA that was significantly differentially expressed between cases and controls at 16 weeks of gestation and six miRNAs that were significantly differentially expressed at 28 weeks. Following qPCR validation, only one miR-206 was found to be significantly increased in 28-week samples in women who later developed preeclampsia (1.4-fold change ±â€Š0.2). The trend for increase in miR-206 expression was mirrored within placental tissue from women with preeclampsia. In parallel, IGF-1, a target gene of miR-206, was also found to be downregulated (0.41 ±â€Š0.04) in placental tissue from women with preeclampsia. miR-206 expression was also detectable in myometrium tissue and trophoblast cell lines. CONCLUSION: Our pilot study has identified miRNA-206 as a novel factor upregulated in preeclampsia within the maternal circulation and in placental tissue.

Differential gene expression in obese pregnancy.

Maternal obesity is a major risk factor for maternal and perinatal complications, and is associated with increased risk of premature cardiovascular death in the offspring. We aimed to identify differentially expressed genes in obese and lean pregnancies. Pregnant women were recruited antenatally and whole-blood samples taken at gestational week 28. Women were classified as lean (BMI<25, n=5), overweight (BMI 25-30, n=11) or obese (BMI>30, n=4). Subcutaneous adipose tissue was obtained from a separate cohort of women undergoing elective Caesarean section (n=3 lean, n=6 overweight, n=9 obese). Total RNA was isolated and gene expression profiled by Illumina microarray technology. Differential gene expression was identified by Ingenuity Pathway Analysis and validated by TaqMan qRT-PCR. In whole blood, differential expression (p<0.05) of six genes (ANGPTL, COX7A2, EIF3A, PTS, CISD1 and GLRX) was identified between lean and non-lean pregnant women by microarray. When gene expression was studied in subcutaneous tissues, we observed a trend towards lower expression of the cytochrome c oxidase-subunit 7A2 gene (COX7A2) in overweight vs lean (p=0.057) and obese vs lean (p=0.06) women, whereas expression was similar between overweight and obese women (p=0.55). Other genes were not differentially expressed across groups. Maternal obesity is associated with differential expression of multiple genes in whole blood. In subcutaneous tissue at term, there was a trend towards reduced COX7A2 expression in obese women. COX7A2 is a mitochondrial protein, with key roles in steroidogenesis and oxidative stress regulation and could provide a link between inflammation and obesity-related pregnancy complications.