Microarray Analysis of Differentially Expressed Fetal Genes in Placental Tissue Derived from Early and Late Onset Severe Pre-eclampsia

Nishizawa, Haruki; Pryor-Koishi, Kanako; Kato, Takema; Kowa, Hiroe; Kurahashi, Hiroki; Udagawa, Yasuhiro

doi:10.1016/j.placenta.2006.05.010

Cited by 147 publications

(122 citation statements)

References 33 publications

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“…Our results corroborate the findings of Sitras et al and Nishizawa et al who both found increased levels of endoglin in PE, but could not differentiate late-and early-onset patient groups with regard to endoglin expression (39,40). s-eng is a placenta-derived TGFbeta co-receptor known to be elevated in PE although reports of circulating s-eng levels correlating with disease severity are not consistent (16).…”

Section: Discussionsupporting

confidence: 80%

Complement activation and regulation in preeclamptic placenta

et al. 2014

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† Anna Inkeri Lokki and Jenni Heikkinen-Eloranta have contributed equally to this work.Preeclampsia (PE) is a common disorder of pregnancy originating in the placenta. We examined whether excessive activation or poor regulation of the complement system at the maternal-fetal interface could contribute to the development of PE. Location and occurrence of complement components and regulators in placentae were analyzed. Cryostat sections of placentae were processed from 7 early-onset PE (diagnosis <34 weeks of gestation), 5 late-onset PE, 10 control pregnancies, and immunostained for 6 complement activators and 6 inhibitors. Fluorescence was quantified and compared between PE and control placentae. Gene copy numbers of complement components C4A and C4B were assessed by a quantitative PCR method. Maternal C4 deficiencies (≥1 missing or nonfunctional C4) were most common in the early-onset PE group (71%), and more frequent in late-onset PE compared to healthy controls (60 vs. 38%). Complement C1q deposition differed significantly between control and patient groups: controls and early-onset PE patients had more C1q than late-onset PE patients (mean p = 0.01 and p = 0.005, respectively). C3 activation was analyzed by staining for C3b/iC3b and C3d. C3d was mostly specific to the basal syncytium and C3b/iC3b diffuse in other structures, but there were no clear differences between the study groups. Activated C4 and membrane-bound regulators CD55, CD46, and CD59 were observed abundantly in the syncytiotrophoblast. Syncytial knots, structures enriched in PE, stained specifically for the classical pathway inhibitor C4bp, whereas the key regulator alternative pathway, factor H (FH) showed a wider distribution in the placenta. Differences in C1q deposition between late-and early-onset PE groups may be indicative of the different etiology of PE symptoms in these patients. Irregular distribution of the complement regulators C4bp and FH in the PE placenta and a higher frequency of C4A deficiencies suggest a disturbed balance between complement activation and regulation in PE.

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Section: Discussionsupporting

confidence: 80%

Complement activation and regulation in preeclamptic placenta

et al. 2014

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“…Both are calciumdependant proteins which activate the NFKB transcription factor family members. Additional array-based studies of the placenta have revealed that a number of other genes involved in intercellular signaling, metabolism, host-pathogen interactions, and apoptosis may have altered expression in PE (19,20). Notable among these is the soluble FMS-related tyrosine kinase-1 (sFLT1), which is upregulated in preeclampsia, leading to increased systemic levels of sFLT1 that fall after delivery (21).…”

Section: Introductionmentioning

confidence: 99%

Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes

Centlow

Carninci²,

Nemeth

et al. 2008

Fertility and Sterility

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Using microarrays made with cDNAs from subtracted placental libraries, we show increased hemoglobin production in the preeclamptic placenta. Heme and hemoglobin may cause endothelial damage and inflammation and drive pathological changes in the placenta if they are released there. Study Objective:To create a library enriched in cDNAs from preeclamptic placentas to print on to microarrays for placental profiling of preeclampsia (PE) and high risk pregnancies. Design: Prospective study.Setting: University women's clinic and academic research laboratory.Patients: Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited.Interventions: Placenta and placenta bed biopsies were collected after delivery. Main Outcome Measures:Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time PCR and histologically using in situ hybridization and immunohistochemistry.Results: 30 genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative rt-PCR. Hemoglobin α2 and γ transcripts were significantly over-expressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin-chains. Conclusions:We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins which cause endothelial damage and inflammation.

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“…To date, a number of microarray studies have been conducted on placental gene expression in preeclampsia and showed that obesity-related genes, cytokine-receptor genes, and apoptosis-related genes are involved in the development of preeclampsia (Centlow et al, 2011;Gack et al, 2005;Han et al, 2006;Heikkila et al, 2005;Herse et al, 2007;Kang et al, 2011;Lee et al, 2010a;Nishizawa et al, 2007;Pang and Xing, 2003a;Reimer et al, 2002;Sitras et al, 2009;Soleymanlou et al, 2005;Tsoi et al, 2003;Zhou et al, 2006;Zhu et al, 2002). However, comparison of different studies done using DNA microarrays has shown poor overlap, and only a minority of differentially-expressed genes are thus shared between them.…”

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confidence: 99%

Identification of Differential Gene Expression Profiles in Placentas from Preeclamptic Pregnancies Versus Normal Pregnancies by DNA Microarrays

Meng

Chen

Sun

et al. 2012

OMICS: A Journal of Integrative Biology

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The purpose of this study was to perform a comprehensive analysis of gene expression profiles in placentas from preeclamptic pregnancies versus normal placentas. Placental tissues were obtained immediately after delivery from women with normal pregnancies (n = 6) and patients with preeclampsia (n = 6). The gene expression profile was assessed by oligonucleotide-based DNA microarrays and validated by quantitative real-time RT-PCR. Functional relationships and canonical pathways/networks of differentially-expressed genes were evaluated by GeneSpring Ô GX 11.0 software, and ingenuity pathways analysis (IPA). A total of 939 genes were identified that differed significantly in expression: 483 genes were upregulated and 456 genes were downregulated in preeclamptic placentas compared with normal placentas (fold change ‡ 2 and p < 0.05 by unpaired t-test corrected with Bonferroni multiple testing). The IPA revealed that the primary molecular functions of these genes are involved in cellular function and maintenance, cellular development, cell signaling, and lipid metabolism. Pathway analysis provided evidence that a number of biological pathways, including Notch, Wnt, NF-jB, and transforming growth factor-b (TGF-b) signaling pathways, were aberrantly regulated in preeclampsia. In conclusion, our microarray analysis represents a comprehensive list of placental gene expression profiles and various dysregulated signaling pathways that are altered in preeclampsia. These observations may provide the basis for developing novel predictive, diagnostic, and prognostic biomarkers of preeclampsia to improve reproductive outcomes and reduce the risk for subsequent cardiovascular disease.

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Microarray Analysis of Differentially Expressed Fetal Genes in Placental Tissue Derived from Early and Late Onset Severe Pre-eclampsia

Cited by 147 publications

References 33 publications

Complement activation and regulation in preeclamptic placenta

Complement activation and regulation in preeclamptic placenta

Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes

Identification of Differential Gene Expression Profiles in Placentas from Preeclamptic Pregnancies Versus Normal Pregnancies by DNA Microarrays

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