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Gene Expression Profiling of Placentas Affected by Pre-Eclampsia
Anne Mette Hoegh,Rehannah Borup,Finn Cilius Nielsen,Steen S rensen,Thomas V. F. Hviid
Journal of Biomedicine and Biotechnology , 2010, DOI: 10.1155/2010/787545
Abstract: Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000) were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events effectuated throughout gestation. They were associated with transcriptional regulation and vasoregulative pathways, along with a number of hypothetical proteins and gene sequences with unknown functions.
Caracteriza o demográfica e morfométrica das síndromes hipertensivas da gesta o  [PDF]
Larissa Faquim Bazaga,Sanívia Aparecida de Lima Pereira,Renata Calciolari Rossi,Camila Lourencini Cavellani
Revista Eletr?nica de Enfermagem , 2009,
Abstract: As Síndromes Hipertensivas da Gesta o (SHG) possuem intensidade variável de acordo com seu tipo. Com este estudoobjetivou-se descrever as características demográficas materno- fetais e as altera es morfométricas placentárias nosdiferentes tipos de SHG, pela análise retrospectiva dos prontuários de pacientes hipertensas, com placentas avaliadasmorfologicamente, processadas para imunohistoquímica utilizando anticorpo monoclonal anti-human CD31 e analisadasmorfometricamente. Os resultados demonstraram que, entre as SHG, os grupos com Hipertens o Cr nica (HC) e Préeclampsiasobreposta à Hipertens o Cr nica (PSHC) apresentaram idade materna superior (p=0,017). A freqüência das SHGfoi superior entre as multíparas. Menor idade gestacional, menores índices de Apgar e pesos placentários inferiores aoesperado para a popula o (p<0,05) foram observados nos casos com Pré-eclampsia (PE) e PSHC. N o houve diferen a nonúmero de vasos das vilosidades tronco placentárias. Nas demais, houve aumento nos casos com PE e Hipertens oGestacional (HGE) e redu o nos casos com PSHC. A importancia do estudo consiste na descri o demográfica e morfológicanas SHG, visando melhorar o atendimento obstétrico e a compreens o dos diferentes tipos de SHG. A gravidade do quadroclínico das SHG tem rela o com maiores intercorrências materno-fetais e com altera es no padr o vascular placentário.
Differential Gene Expression Analysis of Placentas with Increased Vascular Resistance and Pre-Eclampsia Using Whole-Genome Microarrays  [PDF]
M. Centlow,C. Wingren,C. Borrebaeck,M. J. Brownstein,S. R. Hansson
Journal of Pregnancy , 2011, DOI: 10.1155/2011/472354
Abstract: Pre-eclampsia is a pregnancy complication characterized by hypertension and proteinuria. There are several factors associated with an increased risk of developing pre-eclampsia, one of which is increased uterine artery resistance, referred to as “notching”. However, some women do not progress into pre-eclampsia whereas others may have a higher risk of doing so. The placenta, central in pre-eclampsia pathology, may express genes associated with either protection or progression into pre-eclampsia. In order to search for genes associated with protection or progression, whole-genome profiling was performed. Placental tissue from 15 controls, 10 pre-eclamptic, 5 pre-eclampsia with notching, and 5 with notching only were analyzed using microarray and antibody microarrays to study some of the same gene product and functionally related ones. The microarray showed 148 genes to be significantly altered between the four groups. In the preeclamptic group compared to notch only, there was increased expression of genes related to chemotaxis and the NF-kappa B pathway and decreased expression of genes related to antigen processing and presentation, such as human leukocyte antigen B. Our results indicate that progression of pre-eclampsia from notching may involve the development of inflammation. Increased expression of antigen-presenting genes, as seen in the notch-only placenta, may prevent this inflammatory response and, thereby, protect the patient from developing pre-eclampsia. 1. Introduction In the western world, 3–7% of all pregnancies are affected by pre-eclampsia (PE). The etiology of PE is still poorly understood, and several theories have been put forward [1–4]. PE is considered a two-stage disease [5, 6]. The first stage is characterized by poor placentation resulting from shallow invasion of the trophoblasts into the maternal spiral arteries. Instead of the low-resistance high-flow system seen in the normal placenta, the PE placenta has increased resistance, and a decreased blood flow and uneven perfusion leads to hypoxia, ischemia, and reperfusion injuries in the placenta [5, 6]. The second stage of PE is characterized by a general vascular endothelial damage, which eventually affects all maternal organs. Transition from stage one, to stage two of the disease is typically seen before 35 gestational weeks (GW) in early onset PE. Placentas from early onset PE more often show histological pathological findings associated with poor placental perfusion, such as infarcts and chronic inflammation [7]. In contrast, placentas from late-onset PE, manifest after
Vilosite de etiologia desconhecida em placentas de gesta es com hipertens o arterial e de gesta es com recém-nascidos pequenos para a idade gestacional  [cached]
Altemani Albina Milani,Gonzatti Adriana Rocha
Revista da Associa??o Médica Brasileira , 2003,
Abstract: OBJETIVOS: Analisar a freqüência da vilosite de etiologia desconhecida (VED) e suas características histológicas em placentas de gesta es com hipertens o arterial materna e de gesta es com recém-nascidos (RN) pequenos para a idade gestacional. MéTODOS: Foram estudadas 213 placentas de m es e RN sem evidências clínicas ou sorológicas de infec o. Estas placentas foram subdivididas conforme a condi o materna em: normotensas - 151 casos, doen a hipertensiva específica da gravidez (DHEG) - 37 e hipertens o cr nica - 25 e, de acordo com o peso do RN, em: pequenos (PIG)- 38 casos e adequados para a idade gestacional (AIG) - 175. Destas placentas, 81 pertenciam a uma amostra aleatória, que foi utilizada para determinar a freqüência de VED na popula o estudada. Foram retirados oito fragmentos do parênquima placentário e as sec es histológicas foram coradas por HE. Para análise estatística foram utilizados os testes de qui-quadrado e exato de Fisher, sendo p < 0.05 considerado significante. RESULTADOS: A freqüência de VED nas placentas foi de 30,8% na amostra aleatória, 39% nas normotensas, 29,7% nas gesta es com DHEG, 32% nas hipertensas cr nicas, 34,2% nos RN PIG e 37,1% nos RN AIG. Nas placentas de gesta es com hipertens o arterial predominou a vilosite com componente parenquimatoso (DHEG - 27%, hipertens o cr nica - 28%). Este tipo de vilosite também foi a mais comum nas placentas dos RN PIG (31,5%). Em contraste, a vilosite basal sem o componente parenquimatoso predominou nas placentas de normotensas (16,5%) e de RN AIG (14,8%). A maioria das vilosites era de intensidade leve. CONCLUS ES: Na popula o estudada, a freqüência de VED é alta, em torno de 30%. A VED ocorre com freqüências semelhantes em placentas de normotensas, de gesta es com DHEG ou hipertens o cr nica e em RN PIG e AIG, porém a vilosite basal sem o componente parenquimatoso é mais comum em normotensas e RN AIG. é possível que este tipo de vilosite seja resultante de uma estimula o antigênica diferente daquela da vilosite com componente parenquimatoso.
Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction
Haruki Nishizawa, Sayuri Ota, Machiko Suzuki, Takema Kato, Takao Sekiya, Hiroki Kurahashi, Yasuhiro Udagawa
Reproductive Biology and Endocrinology , 2011, DOI: 10.1186/1477-7827-9-107
Abstract: We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8) using a microarray method.A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels.Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia.Pre-eclampsia is one of the most common and potentially serious pregnancy-associated disorders and is a principal cause of maternal morbidity, accounting for almost 15-20% of pregnancy-related mortalities [1]. Pre-eclampsia is not a simple complication of pregnancy, but is a syndrome involving multiple organ failure including that of the liver, kidney, lung, and the coagulatory and neural systems. The prognosis for both the mother and fetus in cases of severe pre-eclampsia is poorer than generally expected, particularly in early onset cases (<34 weeks of gestation) [2]. Although these patients are gener
ECLAMPSIA
TASNEEM ASHRAF
The Professional Medical Journal , 2004,
Abstract: Objective: To evaluate incidence, morbidity andmortality associated with Eclampsia. Design: Prospective study of 98 cases of eclampsia. Setting: departmentof obstetrics and gynaecology unit II Bolan Medical Collage Complex Quetta. Patients: 98 cases were admittedwith eclampsia during two years and six months period from 1st June 2001 to December 2003. Results: Totalno of admissions were 6952. 98 patients presented with eclampsia making a frequency of 1.40%. Of these 98cases of eclampsia 58 % were primigravidas, mean age of eclamptic patients was 34 years. Gestational age atadmission was less than 35 weeks in 80(78.4%) cases. 54(55%) patients had intrapartum eclampsia.64 (66.7%)patients received diazepam and rest received Magnesium sulphate as anticonvulsant. Caesarean section was donein 10 (11.49%) cases rest delivered vaginally. Fetal loss was seen in 72(82.75%) patients, while 7(7.14%) mothersdied of eclampsia. Conclusion: Maternal and perinatal mortality and morbidity is very high in eclempticpatients. Magnesium sulphate is good anticonvulsant, helpful in reducing maternal morbidity and mortalityconsiderably. Good antenatal practices, maternal education and awareness, provision of better health facilitiesand their utilization will definitely improve maternal and fetal outcome.
Vilosite de etiologia desconhecida em placentas de gesta??es com hipertens?o arterial e de gesta??es com recém-nascidos pequenos para a idade gestacional
Altemani, Albina Milani;Gonzatti, Adriana Rocha;
Revista da Associa??o Médica Brasileira , 2003, DOI: 10.1590/S0104-42302003000100036
Abstract: background: the objectives of this study are to analyze the frequency and the histopathological features of the villitis of unknown etiology (vue) in placentas of pregnancies with hypertensive disorders and of small-for-gestational-age infants (sga). methods: two hundred and thirteen placentas from pregnancies without clinical or laboratorial evidence of infection were studied. these cases were subdivided according to: a) maternal condition in: non-complicated pregnancy (ncp)- 151 cases, pregnancy-induced hypertension (pih)- 37 and sustained chronic hypertension (sch)- 25 and b) newborn weight in: small for gestational age (sga)- 38 cases and adequate for gestational age (aga)- 175. of these placentas, 81 belong to the random sample, which was used to determine the frequency of vue in the population studied. eight blocks were taken from placental parenchyma and the histological sections were stained with hematoxylin and eosin. frequency tables of categorical data were analyzed using the chi- square test and fisher test; statistical significance was considered for p< 0.05. results: the frequency of vue in the placentas was 30.8% in the random sample, 39% in ncp, 29.7% in pih, 32% in sch, 34.2% in sga infants and 37.1% in aga infants. placentas of pregnancies with hypertensive disorders were more affected by villitis with parenchymatous component (pih - 27.0%, sch - 28.0%). this lesion was also the predominant villitis in the placentas of the sga infants (31.5%). in contrast, in placentas of ncp and aga infants, the principal kind of villitis was basal, not associated to a parenchymatous component (16.5% and 14.8% respectively). in the majority of the cases the villitis was mild. conclusion: in the population studied, the frequency of vue is high (around 30%). the lesion occurs in a similar frequency in placentas from ncp, pih, sch, sga and aga infants, but basal villitis not associated to a parenchymatous component affects mainly the placentas of ncp and aga infants.
ECLAMPSIA
SHAHIDA SHERAZ
The Professional Medical Journal , 2006,
Abstract: Objective: To evaluate incidence, morbidity and mortalityassociated with eclampsia. Design: A prospective study. Place and Duration: The study which was carried out at PAFHospital Rafiqui, Shorkot spanned over a period of 2 years from Jun 2002-Dec 2004. Patients and Methods: Thestudy comprises of 55 eclamptic cases diagnosed out of 3391 consecutive deliveries, carried out in our hospital.Results: The incidence of eclampsia, in this study, was found to be 1.62%. Out of 55 cases 38(69.1%) patients wereprimigravida. Forty three (78.2%) of the patients were between the ages of 21 to 30 years. In 50(90.9%) patientsgestational age was less than 35 weeks. Thirty seven (67.3%) cases had antepartum eclampsia. Forty four (80%)patients received diazepam while the remaining 11(20%) received magnesium sulphate (MgSO4) as anticonvulsant.Commonest mode of delivery was spontaneous vaginal delivery (31 cases, 56.4%) followed by lower caesareansection (21 cases, 38.2%). Fetal loss was seen in 12(20.7%) cases. Two patients died of eclampsia, maternal mortalityrate being 3.6%. Conclusion: Eclampsia is a life threatening complication of pregnancy. However an improvement inantenatal care, upgrading the neonatal facilities and early delivery by cesarean section can improve the perinataloutcome.
A Comprehensive Survey of miRNA Repertoire and 3′ Addition Events in the Placentas of Patients with Pre-Eclampsia from High-Throughput Sequencing  [PDF]
Li Guo, Qi Yang, Jiafeng Lu, Hailing Li, Qinyu Ge, Wanjun Gu, Yunfei Bai, Zuhong Lu
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021072
Abstract: Background To gain insight into potential roles of isomiR spectrum and isomiRs with 3′ additions in pre-eclampsia, we performed a comprehensive survey of miRNA repertoire and 3′ addition events from placental samples with different degrees of pre-eclampsia by applying SOLiD sequencing platform. Principal Findings Over 30% isomiRs were detected with 3′ non-template additional nucleotides, especially for additional nucleotide of adenosine. However, these modified isomiRs showed a lower percentage of total miRNA expression (<15%). Generally, 1-3 abundant isomiRs from a given miRNA locus were identified, but none of them was detected with 3′ additions. Different miRNAs indicated various isomiR spectrums and expression patterns. The most abundant isomiR spectrum, isomiR profile and expression pattern always were stability, but herein we found several exceptions across samples, especially between normal and diseased samples. At isomiR level, we detected a distinct subset of differentially expressed modified isomiRs between normal and diseased samples or between mild and severe samples. Gene Ontology analysis of their experimentally validated target genes revealed enrichment for specific biological process categories. Conclusions The phenomenon of multiple isomiRs, especially for isomiRs with 3′ additions, is not a random event during pre-miRNA processing. Varieties of isomiRs and expression patterns reveal potential functional implication and should be taken into account. The study enriches association of miRNAs and human disease, including potential roles of various miRNA variants and 3′ addition events.
Press o arterial e concentra o plasmática do peptídeo atrial natriurético e do peptídeo natriurético tipo B, em gesta es complicadas pela pré-eclampsia  [cached]
Reis Zilma Silveira Nogueira,Cabral Ant?nio Carlos Vieira,Barra Juliana Silva,Leite Henrique Vitor
Revista Brasileira de Ginecologia e Obstetrícia , 2003,
Abstract: OBJETIVO: o estudo busca determinar a existência de associa o entre a eleva o da press o arterial e os níveis plasmáticos dos peptídeos natriuréticos ANP e BNP, na gesta o complicada pela pré-eclampsia. MéTODOS: em estudo transversal caso-controle, pareado por idade gestacional, 25 grávidas normotensas e 61 portadoras de pré-eclampsia foram avaliadas quanto ao nível da press o arterial e às concentra es plasmáticas dos peptídeos natriuréticos ANP e BNP. Exames clínico e laboratoriais foram realizados para o diagnóstico de pré-eclampsia, sendo a press o arterial medida de forma n o invasiva. As dosagens hormonais foram obtidas por radioimunoensaio, após extra o em colunas Sep-pak C18. Os valores médios das concentra es plasmáticas do ANP e BNP foram comparados entre grupos com press o arterial progressivamente maiores. A correla o entre os valores da press o arterial e os níveis plasmáticos do ANP e BNP no sangue materno foi também investigada pela de análise de regress o no grupo completo de gestantes e em grupos específicos excluindo-se a hipertens o anterior à gesta o e, em seguida, excluindo-se aquelas sem hipertens o prévia. RESULTADOS: os valores plasmáticos de ANP foram 41.5±7.3, 78.4±13.1 e 89.2±13.4 pg/mL (p<0,00001) e os de BNP plasmático foram 79.5±15.8, 176.7±42.2 e 208.3±63.5 pg/mL (p=0,005), respectivamente, para os grupos de press o arterial média =107 mmHg, 107-139 mmHg e =140 mmHg. Verificou-se correla o positiva entre as concentra es plasmáticas do ANP e os níveis pressóricos na pré-eclampsia, independente da existência de estado hipertensivo prévio à gesta o (p<0,0001 para pré-eclampsia e p<0,01 para pré-eclampsia sobreposta à hipertens o arterial cr nica), ao passo que as dosagens de BNP n o se mostraram associadas à press o arterial no grupo com hipertens o arterial prévia à gesta o (p=0,004 para pré-eclampsia e p=0,18 para pré-eclampsia sobreposta à hipertens o arterial cr nica). CONCLUS O: o agravamento da hipertens o na pré-eclampsia correlacionou-se com as concentra es séricas do ANP e BNP, embora os valores do BNP possam ser influenciados pela existência de estado hipertensivo prévio.
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