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2.
Placenta ; 48 Suppl 1: S17-S20, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27506263

RESUMO

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At the 2015 IFPA annual meeting there were 12 themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology and collectively covered areas of obesity and the placenta, stem cells of the feto-maternal interface, and placental immunobiology and infection.


Assuntos
Obesidade/metabolismo , Doenças Placentárias/metabolismo , Placenta/metabolismo , Células-Tronco/metabolismo , Feminino , Humanos , Gravidez
3.
Reproduction ; 150(5): 449-62, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26248480

RESUMO

The placenta is responsible for all nutrient and gas exchange between mother and baby during pregnancy. The differentiation of specialised placental epithelial cells called trophoblasts is essential for placental function, but we understand little about how these populations arise. Mouse trophoblast stem cells have allowed us to understand many of the factors that regulate murine trophoblast lineage development, but the human placenta is anatomically very different from the mouse, and it is imperative to isolate a human trophoblast stem cell to understand human placental development. Here we have developed a novel methodology to isolate a Hoechst side-population of trophoblasts from early gestation placentae and compared their transcriptome to differentiated trophoblast populations (cytotrophoblasts and extravillous trophoblasts) using microarray technology. Side-population trophoblasts clustered as a transcriptomically distinct population but were more closely related to cytotrophoblasts than extravillous trophoblasts. Side-population trophoblasts up-regulated a number of genes characteristic of trophectoderm and murine trophoblast stem cells in comparison to cytotrophoblasts or extravillous trophoblasts and could be distinguished from both of these more mature populations by a unique set of 22 up-regulated genes, which were enriched for morphogenesis and organ development and the regulation of growth functions. Cells expressing two of these genes (LAMA2 and COL6A3) were distributed throughout the cytotrophoblast layer at the trophoblast/mesenchymal interface. Comparisons to previously published trophoblast progenitor populations suggest that the side-population trophoblasts isolated in this work are a novel human trophoblast population. Future work will determine whether these cells exhibit functional progenitor/stem cell attributes.


Assuntos
Diferenciação Celular , Separação Celular/métodos , Vilosidades Coriônicas/crescimento & desenvolvimento , Placenta/citologia , Placentação/fisiologia , Células-Tronco/citologia , Trofoblastos/citologia , Animais , Proliferação de Células , Células Cultivadas , Vilosidades Coriônicas/metabolismo , Feminino , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Técnicas Imunoenzimáticas , Camundongos , Placenta/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células-Tronco/metabolismo , Trofoblastos/metabolismo
4.
Placenta ; 35(3): 195-201, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24522232

RESUMO

INTRODUCTION: Galectins are expressed at the fetal-maternal interface and have multiple roles including during blastocyst implantation. The expression of galectin-7 however has not been investigated in the uterus. We aimed to localise galectin-7 to the endometrium of women with normal fertility and with a history of miscarriage and prospectively determine whether serum levels are altered in women who subsequently miscarry. We also investigated the role of galectin-7 on trophoblast-endometrial epithelial cell adhesion. METHODS: Immunohistochemistry localised galectin-7 to endometrium throughout the menstrual cycle in women (normal fertility or with history of miscarriage) and in first trimester implantation sites. Galectin-7 serum levels were determined by ELISA. We used both endometrial epithelial-trophoblast cell lines and primary cells for cell-cell adhesion experiments. RESULTS: Galectin-7 immunolocalized to endometrial luminal and glandular epithelium in normally fertile women and was upregulated in epithelium and stroma of women with a history of miscarriage. Similarly, galectin-7 serum levels were elevated at 6 weeks gestation in women who subsequently miscarried compared to gestation matched controls. Exogenous galectin-7 reduced endometrial epithelial-trophoblast adhesion in cell-line and primary cell assays. However, when endometrial epithelial cells were isolated from women with endometrial disorders, galectin-7 increased epithelial-trophoblast adhesion. CONCLUSIONS: Galectin-7 is produced by endometrial epithelium and is abnormally elevated in the endometrium of women with a history of miscarriage. Serum levels may be useful as a predictive biomarker of miscarriage. Our data suggests that galectin-7 facilitates adhesion of the embryo to the endometrium and elevated galectin-7 may result in abnormal adhesion.


Assuntos
Biomarcadores/metabolismo , Implantação do Embrião/fisiologia , Galectinas/fisiologia , Aborto Habitual/metabolismo , Aborto Espontâneo/metabolismo , Adulto , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Endométrio/metabolismo , Feminino , Galectinas/biossíntese , Galectinas/sangue , Humanos , Ciclo Menstrual , Gravidez , Primeiro Trimestre da Gravidez
5.
Gene ; 539(1): 168-72, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24508274

RESUMO

We report a 20-month-old girl ascertained at the age of 11 months for developmental delay. She presented with hypotonia and delayed motor development. The patient had severe language impairment and showed behaviour consistent with autism spectrum disorder. She was microcephalic with mild dysmorphic features and had joint hyperlaxity. We detected a 2.3 Mb de novo deletion in 2q24.2q24.3 on her paternal chromosome. We compare the clinical features of our patient to six previously published patients with a deletion in 2q24.2q24.3, and one patient reported in the ECARUCA database. Although the clinical presentation of these patients is not highly consistent, likely due to the different deletion size and gene content, the following features seem to be recurrent: disturbance in the central nervous system, poor growth, hypotonia, and joint hyperlaxity. The region deleted in our patient contains 13 genes including PSMD14, TBR1, SLC4A10, DPP4, KCNH7, and FIGN. We briefly review the knowledge of these genes and their possible involvement in the aetiology of this developmental delay syndrome.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 2/genética , Deficiências do Desenvolvimento/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Feminino , Humanos , Lactente , Instabilidade Articular/genética , Transtornos do Desenvolvimento da Linguagem/genética , Hipotonia Muscular/genética
6.
Gene ; 533(1): 403-10, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24095780

RESUMO

Chromosomal rearrangements resulting in an inverted duplication and a terminal deletion (inv dup del) can occur due to three known mechanisms, two of them resulting in a normal copy region between the duplicated regions. These mechanisms involve the formation of a dicentric chromosome, which undergo breakage during cell division resulting in cells with either an inverted duplication and deletion or a terminal deletion. We describe a mosaic 3 year old patient with two cell lines carrying a chromosome 9p deletion where one of the cell lines contains an additional telocentric marker chromosome. Our patient is mosaic for the product of a double breakage of a dicentric chromosome including a centric fission. Mosaicism involving different rearrangements of the same chromosome is rare and suggests an early mitotic breakage event. Chr9p terminal deletions associated with duplications have previously been reported in 11 patients. We compare the clinical features of all 12 patients including the patient that we report here. To the best to our knowledge this is a first case reported where the double breakage occurred in the dicentric derivative chromosome 9.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 9 , Mosaicismo , Zigoto , Pré-Escolar , Humanos , Cariotipagem , Masculino
7.
Neuropharmacology ; 62(2): 1019-27, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22051632

RESUMO

Marijuana's effects in humans are most often reported as intoxicating or therapeutic; yet, some humans report dysphoria or other negative affect. To evaluate whether differences in endocannabinoid levels might account for this variability, the present study examined whether sensitivity to cannabinoids changed when anandamide (AEA) metabolism was inhibited through administration of phenylmethyl sulfonyl fluoride (PMSF) a non-specific irreversible amidase inhibitor. Male Long Evans rats were trained to discriminate 3 mg/kg Δ(9)-tetrahydrocannabinol (THC) versus vehicle in 2-lever drug discrimination procedure. ED(50)s for THC and CP 55,940 were lower when administered with PMSF than alone. PMSF administration also potentiated characteristic cannabimimetic effects of THC in ICR mice. Potentiation of AEA's in vivo effects by PMSF were also observed, primarily as a consequence of PMSF inhibition of the enzyme fatty acid amide hydrolase. Enhancement of the effects of THC and CP 55,940 through this mechanism is unlikely, as these cannabinoids are predominantly metabolized through the P450 system. Mass spectrometry revealed that, in the presence of THC, endogenous AEA levels in the brain decreased and that this decrease was prevented by PMSF, suggesting that increased AEA levels may have acted additively with exogenously administered cannabinoids to increase cannabimimetic effects. These findings may account for the varying affect in response to marijuana in humans or cannabinoids in animals while also suggesting that metabolic inhibitors of AEA may potentiate marijuana's intoxicating effects in humans. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.


Assuntos
Encéfalo/metabolismo , Moduladores de Receptores de Canabinoides/metabolismo , Aprendizagem por Discriminação/efeitos dos fármacos , Dronabinol/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Encéfalo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fluoreto de Fenilmetilsulfonil/farmacologia , Inibidores de Proteases/farmacologia , Ratos , Ratos Long-Evans , Receptor CB1 de Canabinoide/metabolismo
8.
J Pharmacol Exp Ther ; 334(1): 137-46, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20400469

RESUMO

Incorporation of the alpha5 nicotinic acetylcholine receptor (nAChR) subunit can greatly influence nAChR function without altering receptor number. Although few animal studies have assessed the role of the alpha5 nAChR in nicotine-mediated behaviors, recent evidence suggests an association between polymorphisms in the alpha5 nAChR gene and nicotine dependence phenotypes in humans. Thus, additional studies are imperative to elucidate the role and function of the alpha5 nAChR subunit in nicotine dependence. Using alpha5(-/-) mice, the current study aimed to examine the role of alpha5 nAChRs in the initial pharmacological effects of nicotine, nicotine reward using the conditioned place preference model, and the discriminative effects of nicotine using a two-lever drug discrimination model. (86)Rb(+) efflux and (125)I-epibatidine binding assays were conducted to examine the effect of alpha5 nAChR subunit deletion on expression and activity of functional nAChRs. Results show that alpha5(-/-) mice are less sensitive to the initial effects of nicotine in antinociception, locomotor activity, and hypothermia measures and that the alpha5 nAChR is involved in nicotine reward. Alternatively, alpha5(-/-) mice did not differ from wild-type littermates in sensitivity to the discriminative stimulus effects of nicotine. Furthermore, deletion of the alpha5 nAChR subunit resulted in a statistically significant decrease in function in the thalamus and hindbrain, but the decreases noted in spinal cord were not statistically significant. Receptor number was unaltered in all areas tested. Taken together, results of the study suggest that alpha5 nAChRs are involved in nicotine-mediated behaviors relevant to development of nicotine dependence.


Assuntos
Comportamento Animal/efeitos dos fármacos , Nicotina/farmacologia , Receptores Nicotínicos/fisiologia , Analgésicos Opioides/farmacologia , Animais , Temperatura Corporal , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Hipotermia/induzido quimicamente , Hipotermia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Dor/metabolismo , Limiar da Dor/efeitos dos fármacos , Ligação Proteica , Receptores Nicotínicos/genética , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
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