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2.
Gene ; 749: 144721, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32360842

RESUMO

Fetal development is critically dependent on the efficiency of the placenta. Porcine trophoblast cell proliferation and invasion have crucial roles in placental fold development, which is one of the essential events determining placental efficiency. The membrane serine proteinase inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1) can regulate cellular invasion and motility in different types of epithelial cells, including trophoblast cells in mice. This work used quantitative polymerase chain reaction (qPCR) and immunohistochemistry to compare the expression level and location of HAI-1 in the placenta on gestational days 26, 50, and 95 in Yorkshire and Meishan pigs. The role of HAI-1 in porcine trophoblast cell (PTr2) proliferation, invasion, and migration in vitro was investigated by analyzing the effects of HAI-1 gene silencing or overexpression. Polymorphism in the HAI-1gene was detected to determine associations between the genotype and piglet birth weight in 400 healthy pure-bred Yorkshire piglets. qPCR results showed that HAI-1 mRNA levels significantly increased (P < 0.01) between gestational days 26 and 50 and then decreased (P < 0.01) between days 50 and 95 in both Meishan and Yorkshire pigs. Immunohistochemical analysis showed that HAI-1 protein was strongly expressed by the high columnar trophoblast cells located at the top of the placental folds with low proliferative and invasion capacities. However, it was expressed at very low levels in cuboidal trophoblast cells located at the side and base of the placental folds with high proliferative and invasion capacities. In vitro experiments indicated that HAI-1 had the ability to reduce the proliferation, invasion and migration of trophoblast cells. In addition, one single-nucleotide polymorphism (SNP) of HAI-1 showed a significant association (P < 0.05) with piglet birth weight. These results revealed that HAI-1 could be a vital molecule in placental folds development by regulating trophoblast proliferation and invasion in pigs.


Assuntos
Placenta/metabolismo , Placentação , Proteínas Secretadas Inibidoras de Proteinases/fisiologia , Sus scrofa/embriologia , Trofoblastos/fisiologia , Animais , Linhagem Celular , Movimento Celular , Proliferação de Células , Feminino , Placentação/genética , Polimorfismo de Nucleotídeo Único , Gravidez , Proteínas Secretadas Inibidoras de Proteinases/genética , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , RNA Mensageiro/metabolismo , Sus scrofa/genética , Sus scrofa/metabolismo , Trofoblastos/citologia
4.
Am J Clin Pathol ; 154(1): 23-32, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32441303

RESUMO

OBJECTIVES: To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. METHODS: Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. RESULTS: Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased.The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. CONCLUSIONS: Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.


Assuntos
Infecções por Coronavirus/patologia , Placenta/patologia , Pneumonia Viral/patologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Betacoronavirus , Estudos de Casos e Controles , Feminino , Humanos , Pandemias , Placenta/irrigação sanguínea , Placenta/virologia , Gravidez , Terceiro Trimestre da Gravidez
5.
Pediatr Dev Pathol ; 23(3): 177-180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32397896

RESUMO

This study describes the pathology and clinical information on 20 placentas whose mother tested positive for the novel Coronovirus (2019-nCoV) cases. Ten of the 20 cases showed some evidence of fetal vascular malperfusion or fetal vascular thrombosis. The significance of these findings is unclear and needs further study.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Doenças Placentárias/etiologia , Doenças Placentárias/patologia , Placenta/patologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Complicações Infecciosas na Gravidez/patologia , Trombose/etiologia , Adolescente , Adulto , Feminino , Doenças Fetais/etiologia , Doenças Fetais/patologia , Humanos , Recém-Nascido , New York , Pandemias , Gravidez , Trombose/patologia , Adulto Jovem
6.
Science ; 368(6487): 181-186, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32273467

RESUMO

Embryonic development is a complex process that is unamenable to direct observation. In this study, we implanted a window to the mouse uterus to visualize the developing embryo from embryonic day 9.5 to birth. This removable intravital window allowed manipulation and high-resolution imaging. In live mouse embryos, we observed transient neurotransmission and early vascularization of neural crest cell (NCC)-derived perivascular cells in the brain, autophagy in the retina, viral gene delivery, and chemical diffusion through the placenta. We combined the imaging window with in utero electroporation to label and track cell division and movement within embryos and observed that clusters of mouse NCC-derived cells expanded in interspecies chimeras, whereas adjacent human donor NCC-derived cells shrank. This technique can be combined with various tissue manipulation and microscopy methods to study the processes of development at unprecedented spatiotemporal resolution.


Assuntos
Embrião de Mamíferos/citologia , Embrião de Mamíferos/fisiologia , Desenvolvimento Embrionário , Microscopia Intravital/métodos , Crista Neural , Animais , Encéfalo/embriologia , Encéfalo/fisiologia , Divisão Celular , Movimento Celular , Quimera/embriologia , Quimera/fisiologia , Eletroporação , Feminino , Técnicas de Transferência de Genes , Camundongos , Camundongos Transgênicos , Neovascularização Fisiológica , Crista Neural/irrigação sanguínea , Crista Neural/citologia , Crista Neural/embriologia , Placenta/fisiologia , Gravidez , Retina/embriologia , Retina/fisiologia , Transmissão Sináptica , Útero
7.
Curr Opin Anaesthesiol ; 33(3): 368-373, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32324666

RESUMO

PURPOSE OF REVIEW: This review describes maternal and fetal anesthetic management for noncardiac fetal surgical procedures, including the management of lower urinary tract obstruction, congenital diaphragmatic hernia (CDH), myelomeningocele, sacrococcygeal teratoma, prenatally anticipated difficult airway and congenital lung lesions. RECENT FINDINGS: Fetal interventions range from minimally invasive fetoscopic procedures to mid-gestation open surgery, to ex-utero intrapartum treatment procedure. Anesthetic management depends on the fetal intervention and patient characteristics. Anesthesia for most minimally invasive procedures can consist of intravenous sedation and local anesthetic infiltration in clinically appropriate maternal patients. Open fetal and ex-utero intrapartum treatment procedures require maternal general anesthesia with volatile anesthetic and other medications to maintain uterine relaxation. Tracheal balloons are a promising therapy for CDH and can be inserted via minimally invasive techniques. Management of the prenatally anticipated difficult airway during delivery and removal of tracheal balloons from patients with CDH during delivery can be clinically dynamic and require flexibility, seamless communication and a high-functioning, multidisciplinary care team. SUMMARY: Maternal and fetal anesthetic management is tailored to the fetal intervention and the underlying health of the fetus and mother.


Assuntos
Anestesia/métodos , Doenças Fetais/cirurgia , Transfusão Feto-Fetal/cirurgia , Fetoscopia/métodos , Hérnias Diafragmáticas Congênitas/terapia , Placenta/irrigação sanguínea , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/terapia , Fetoscopia/efeitos adversos , Feto/cirurgia , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Doenças Placentárias/cirurgia , Gravidez , Cuidado Pré-Natal , Diagnóstico Pré-Natal
8.
Wiad Lek ; 73(2): 215-219, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248147

RESUMO

OBJECTIVE: The aim: To study the pathomorphological characteristics and immunohistochemical features of placentae from human immunodeficiency virus-positive (HIV-positive) pregnant women with FGR. PATIENTS AND METHODS: Materials and methods: The study material was 32 placentae, including 12 placentae from HIV-positive pregnant women with FGR (study group), 10 placentae from HIVpositivepregnant women without FGR (comparison group) and 10 placentae from HIV-negative women with physiological pregnancy (control group). An immunohistochemical study was performed using monoclonal antibodies (MCA) against CD31+ and vascular endothelial growth factor (VEGF). RESULTS: Results: Pathomorphologic changes of the placentae from HIV-positive pregnant women with FGR were characterized by edema in the umbilical cord tissue, partial dissection of the vascular wall fibers, dysmucoidosis; intracellular edema and hemorrhage in the fetal membrane tissues. In the placentae tissue it was found marked manifestations of degenerative changes in the form of the areas of fibrinoid necrosis, pronounced manifestations of dysmucoidosis, vacuolation of the villi stroma, an increase in the number of avascular villi and immature villi of small caliber with the phenomena of syncytiotrophoblast focal hyperplasia. An immunohistochemical study with MCA against CD31+ revealed the expression (optical density) of the vascular endothelial cells up to 2 points, and the expression level up to 3 points in the isolated areas with the appearance of the expression on the villi surface and in their thickness. During immunohistochemical studies with VEGF the expression level and its optical density increased up to 2-3 points, in some areas the expression of deposits were detected on the villi surface, in their thickness and in the intervillous space. CONCLUSION: Conclusions: The comparative pathomorphological and immunohistochemical study of the placentae demonstrated more significant changes in the group of HIV-positive pregnant women with FGR. In the placentae of HIV-positive pregnant women with FGR immunohistochemical examinations revealed a high level of CD31+ and VEGF expression.


Assuntos
Retardo do Crescimento Fetal , Soropositividade para HIV , Células Endoteliais , Feminino , Humanos , Placenta , Gravidez , Fator A de Crescimento do Endotélio Vascular
9.
Ultrasound Obstet Gynecol ; 55(6): 835-837, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249471

RESUMO

Imaging modalities play a crucial role in the management of suspected COVID-19 patients. Before reverse transcription polymerase chain reaction (RT-PCR) test results are positive, 60-93% of patients have positive chest computed tomographic (CT) findings consistent with COVID-19. We report a case of positive lung ultrasound findings consistent with COVID-19 in a woman with an initially negative RT-PCR result. The lung ultrasound-imaging findings were present between the negative and subsequent positive RT-PCR tests and correlated with CT findings. The point-of-care lung-ultrasound examination was easy to perform and, as such, could play an important role in the triage of women with suspected COVID-19. The neonatal swabs, cord blood and placental swab RT-PCR tests were negative for SARS-CoV-2, a finding consistent with the published literature suggesting no vertical transmission of this virus in pregnant women. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Cesárea , Angiografia por Tomografia Computadorizada , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Diagnóstico Diferencial , Feminino , Sangue Fetal/virologia , Humanos , Leite Humano/virologia , Pandemias , Placenta/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Testes Imediatos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Embolia Pulmonar/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios X
10.
Cell Prolif ; 53(5): e12802, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32291850

RESUMO

OBJECTIVES: During human pregnancy, the endothelial cells of the uterine spiral arteries (SPA) are extensively replaced by a subtype of placental trophoblasts, endovascular extravillous trophoblasts (enEVTs), thus establishing a placental-maternal circulation. On this pathway, foetus-derived placental villi and enEVTs bath into the maternal blood that perfuses along SPA being not attacked by the maternal lymphocytes. We aimed to reveal the underlying mechanism of such immune tolerance. METHODS: In situ hybridization, immunofluorescence, ELISA and FCM assay were performed to examine TGF-ß1 expression and distribution of regulatory T cells (Tregs) along the placental-maternal circulation route. The primary enEVTs, interstitial extravillous trophoblasts (iEVTs) and decidual endothelial cells (dECs) were purified by FACS, and their conditioned media were collected to treat naïve CD4+ T cells. Treg differentiation was measured by FLOW and CFSE assays. RESULTS: We found that enEVTs but not iEVTs or dECs actively produced TGF-ß1. The primary enEVTs significantly promoted naïve CD4+ T-cell differentiation into immunosuppressive FOXP3+ Tregs, and this effect was dependent on TGF-ß1. In recurrent spontaneous abortion (RSA) patients, an evidently reduced proportion of TGF-ß1-producing enEVTs and their ability to educate Tregs differentiation were observed. CONCLUSIONS: Our findings demonstrate a unique immune-regulatory characteristic of placental enEVTs to develop immune tolerance along the placental-maternal circulation. New insights into the pathogenesis of RSA are also suggested.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Placenta/imunologia , Linfócitos T Reguladores/imunologia , Trofoblastos/imunologia , Adulto , Animais , Células Endoteliais/imunologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Fator de Crescimento Transformador beta1/imunologia
11.
Life Sci ; 253: 117668, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32320706

RESUMO

AIMS: Preeclampsia (PE) accounts for the foremost cause of maternal and fetal mortality worldwide, whereas, there are no effective treatments for the disease yet. Long non-coding RNAs (lncRNAs) play critical roles in various human disorders, including PE. Here, we identified an up-regulated lncRNA HOTAIR, and explored its underlying mechanisms in PE. MAIN METHODS: qRT-PCR analysis was used to examine HOTAIR expression in PE tissues and cell lines. Trophoblast proliferation was examined by colony formation and 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assays. Trophoblast migration and invasion was determined by transwell and wound healing assays. Bioinformatics analysis was performed to verify the regulation HOTAIR on miRNAs. The interaction between HOTAIR and EZH2 was detected using RNA immunoprecipitation assay (RIP). Chromatin immunoprecipitation (CHIP) assay was also performed to verify that the negative regulation of HOTAIR on miR-106a was dependent on the epigenetic repressor EZH2. KEY FINDINGS: HOTAIR was up-regulated in PE placenta tissues, which repressed the proliferation, migration and invasion of trophoblast cells. HOTAIR significantly repressed miR-106a expression and the reduced miR-106a level was also observed in placentas from PE patients. Additionally, miR-106a mimic enhanced the migration and invasion of trophoblast cells. Further mechanistic analyses implied that the action of HOTAIR is moderately attributable to its repression of miR-106a via association with EZH2. SIGNIFICANCE: High level of HOTAIR repressed the proliferation, migration and invasion of trophoblast cells through targeting miR-106 in an EZH2-dependent manner, which may provide new insights into the roles of HOTAIR and miR-106a as potential regulators in PE.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , MicroRNAs/metabolismo , Pré-Eclâmpsia/metabolismo , RNA Longo não Codificante/metabolismo , Sequência de Bases , Linhagem Celular , Proliferação de Células , Progressão da Doença , Repressão Epigenética , Feminino , Humanos , Placenta/metabolismo , Gravidez , Trofoblastos/citologia , Regulação para Cima
13.
Gene ; 739: 144512, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32112983

RESUMO

Pleckstrin homology-like domain family A member 2 (PHLDA2) is essential for placental development in mammals. This study was conducted to investigate transcriptional regulation of goat PHLDA2 in the placenta. Real-time PCR and Western blot analyses showed different expression of the PHLDA2 in goat placentas during gestation with highest expression at 30 and 45 days post coitus (P < 0.05). Luciferase reporter assays demonstrated the highest promoter activity in the region of -1023/+20 (P < 0.05). A CpG island was defined within -631/+379 region, where lower level of CpG-methylation was detected with bisulfite sequencing PCR in the placenta than that in the spleen and liver (P < 0.05). Meanwhile, in vitro experiments showed that 5-AzaC enhanced the gene expression in a dose-dependent manner. Site-directed mutation in vitro demonstrated that transcription factor Ying-yang 1 (YY1) had an inhibitory effect on the PHLDA2 expression, and the inhibition was further confirmed with overexpression and siRNA constructs of YY1. ChIP and RE-ChIP analyses further identified the binding of YY1 to the PHLDA2 promoter by interaction with histone deacetylase 1 (HDAC1) and HDAC3. This study uncovers the negative regulation of the CpG-methylation and YY1 on goat PHLDA2 expression. YY1 prefers binding to CpG-methylation sequences, and inhibits goat PHLDA2 expression via recruiting HDAC1 and 3.


Assuntos
Regulação da Expressão Gênica , Cabras/genética , Histona Desacetilase 1/metabolismo , Histona Desacetilases/metabolismo , Proteínas Nucleares/metabolismo , Fator de Transcrição YY1/metabolismo , Animais , Ilhas de CpG/genética , Metilação de DNA , Feminino , Histona Desacetilase 1/genética , Histona Desacetilases/genética , Proteínas Nucleares/genética , Placenta , Gravidez , Regiões Promotoras Genéticas/genética , Fator de Transcrição YY1/genética
14.
Toxicol Lett ; 326: 70-77, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32113805

RESUMO

In addition to the transfer across the placenta, placenta displays hormonal and xenobiotic metabolism, as well as enzymatic defense against oxidative stress. We analyzed aromatase (CYP19A1), uridine 5'-diphospho-glucuronyltransferase (UGT), glutathione-S-transferase (GST) and catalase (CAT) activities in over 70 placentas from nonsmokers stored at -80 °C from former perfusion studies. A wide interindividual variation in all activities was found. Longterm storage at -80 °C did not affect the activities. Ethoxyresorufin-O-deethylase (EROD, CYP1A1) was not detected in any of the studied placentas perfused with chemicals. Several compounds in placental perfusion changed statistically significantly the enzyme activities in placental tissue. Melamine and nicotine increased CYP19A1, melamine increased UGT and GST, PhIP with ethanol decreased CYP19A1 and increased GST, and PhIP with buprenorphine decreased CAT. Antipyrine in 100 µg/ml also changed the studied enzyme activities, but not statistically significantly. Because antipyrine is a reference compound in placental perfusions, its potential effects must be taken into account in human placental perfusion. Enzyme activities deserve further studies as biomarkers of placental toxicity. Finally, enzyme activities deserve further studies as biomarkers of placental toxicity.


Assuntos
Antipirina/metabolismo , Aromatase/metabolismo , Catalase/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Glucuronosiltransferase/metabolismo , Glutationa Transferase/metabolismo , Placenta/metabolismo , Adulto , Feminino , Humanos , Gravidez
15.
PLoS One ; 15(3): e0229904, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142542

RESUMO

The placental epigenome plays a critical role in regulating mammalian growth and development. Alterations to placental methylation, often observed at imprinted genes, can lead to adverse pregnancy complications such as intrauterine growth restriction and preterm birth. Similar associations have been observed in offspring derived from advanced paternal age fathers. As parental age at time of conception continues to rise, the impact of advanced paternal age on these reproductive outcomes is a growing concern, but limited information is available on the molecular mechanisms affected in utero. This longitudinal murine research study thus investigated the impact of paternal aging on genomic imprinting in viable F1 embryonic portions of the placentas derived from the same paternal males when they were young (4-6 months) and when they aged (11-15 months). The use of a controlled outbred mouse model enabled analysis of offspring throughout the natural lifetime of the same paternal males and excluded confounding factors like female age or infertility. Firstly, paternal age significantly impacted embryonic placental weight, fetal weight and length. Targeted bisulfite sequencing was utilized to examine imprinted methylation at the Kcnq1ot1 imprinting control region, with significant hypermethylation observed upon natural paternal aging. Quantitative real-time PCR assessed imprinted gene expression levels at various imprinting clusters, resulting in transcript level alterations attributable to advanced paternal age. In summary, our results demonstrate a paternal age effect with dysregulation at numerous imprinted loci, providing a mechanism for future adverse placental and offspring health conditions.


Assuntos
Epigênese Genética , Impressão Genômica/genética , Idade Paterna , Reprodução/genética , Animais , Metilação de DNA/genética , Epigenoma/genética , Pai , Feminino , Humanos , Infertilidade/genética , Infertilidade/patologia , Masculino , Camundongos , Placenta/metabolismo , Placenta/patologia , Gravidez
16.
PLoS One ; 15(3): e0230000, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126118

RESUMO

BACKGROUND: Placental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms. METHODS: Serum levels of placenta-related proteins-leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice. RESULTS: An elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs. CONCLUSIONS: Serum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model.


Assuntos
Pré-Eclâmpsia/sangue , Adulto , Animais , Biomarcadores/sangue , Feminino , Idade Gestacional , Humanos , Camundongos , Placenta/metabolismo , Gravidez , Estudos Retrospectivos
17.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(3): 387-392, 2020 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-32174088

RESUMO

Objective: To investigate the effects of human placental mesenchymal stem cells (hPMSCs) transplantation on pulmonary vascular endothelial permeability and lung injury repair in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: The hPMSCs were isolated from the human placental tissue by enzyme digestion and passaged. The cell phenotype of the 3rd generation hPMSCs was detected by flow cytometry. Twenty-four 6-week-old healthy male C57BL/6 mice were randomly divided into 3 groups ( n=8). The mice were instilled with LPS in the airway to prepare an ALI model in the ALI model group and the hPMSCs treatment group, and with saline in the control group. At 12 hours after LPS infusion, the mice were injected with 3rd generation hPMSCs via the tail vein in hPMSCs treatment group and with saline in the ALI model group and the control group. At 24 hours after injection, the lung tissues of all mice were taken. The pathological changes were observed by HE staining. The wet/dry mass ratio (W/D) of lung tissue was measured. The Evans blue leak test was used to detect the pulmonary vascular endothelial permea bility in mice. The expression of lung tissue permeability-related protein (VE-cadherin) was detected by Western blot. Results: Flow cytometry examination showed that the isolated cells had typical MSCs phenotypic characteristics. Mice in each group survived. The alveolar structure of the ALI model group significantly collapsed, a large number of inflammatory cells infiltrated, and local alveolar hemorrhage occurred; while the alveolar structure collapse of the hPMSCs treatment group significantly improved, inflammatory cells infiltration significantly reduced, and a few red blood cells were in the interstitial lung. W/D and exudation volume of Evans blue stain were significantly higher in the ALI model group than in the control group and the hPMSCs treatment group ( P<0.05), in the hPMSCs treatment group than in the control group ( P<0.05). The relative protein expression of VE-cadherin was significantly lower in the ALI model group than in the control group and the hPMSCs treatment group ( P<0.05), and in the hPMSCs treatment group than in the control group ( P<0.05). Conclusion: Intravenous injection of hPMSCs can effectively reduce the increased pulmonary vascular endothelial permeability mediated by LPS, relieve the degree of lung tissue damage, and play a therapeutic role in ALI mice.


Assuntos
Lesão Pulmonar Aguda/terapia , Endotélio Vascular/fisiologia , Transplante de Células-Tronco Mesenquimais , Animais , Feminino , Humanos , Lipopolissacarídeos , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade , Placenta/citologia , Gravidez , Distribuição Aleatória
18.
PLoS One ; 15(3): e0230488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176740

RESUMO

Pregnant women with diabetes mellitus (DM) are at high risk for hypertensive disorder of pregnancy (HDP). Women with poor control DM sometimes have heavy-for-dates infants. However, women with HDP sometimes have light-for-dates infants. We aim to clarify the relationship between glycemic control and fetal growth in women with DM and/or subsequent HDP. Of 7893 women gave singleton birth at or after 22 gestational weeks, we enrolled 154 women with type 1 DM (T1DM) or type 2 DM (T2DM) whose infants did not have fetal abnormalities. Among women with T1DM or T2DM, characteristics of the three groups (with HDP, without HDP, and with chronic hypertension [CH]) were compared. No women with T1DM had CH, but 19 (17.4%) of 109 with T2DM did. HDP incidence was similar between women with T1DM (22.2%) and T2DM without CH (16.7%). Among women with T1DM, the incidences of fetal growth restriction (FGR) with and without HDP were similar. However, among women with T2DM without CH, this incidence was significantly higher among those with HDP (33.3%) than among those without HDP (5.3%), was significantly more common with HbA1c levels at first trimester ≥ 7.2% (33.3%) than with those < 7.2% (5.6%), and significantly more numerous without pre-pregnancy therapies for DM (23.3%) than with them (3.3%). Among women with T2DM and HDP, those with FGR had smaller placenta SDs and higher insulin dosages at delivery than those without light-for-dates. In multivariate analysis, the presence of diabetic nephropathy was a predictor of T1DM and HDP (P = 0.0105), whereas HbA1c levels ≥ 7.2% before pregnancy was a predictor of T2DM and HDP (P = 0.0009). Insulin dosage ≥ 50U/day at delivery (P = 0.0297) and the presence of HDP (P = 0.0116) independently predicted T2DM, HDP, and FGR development. Insufficient pre-pregnancy treatment of DM increased the risk of HDP.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Retardo do Crescimento Fetal , Insulina/administração & dosagem , Pré-Eclâmpsia , Gravidez em Diabéticas , Adulto , Doença Crônica , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/patologia , Humanos , Placenta/metabolismo , Placenta/patologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/patologia , Gravidez , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/tratamento farmacológico , Gravidez em Diabéticas/epidemiologia , Gravidez em Diabéticas/patologia , Estudos Retrospectivos , Fatores de Risco
19.
Rev Bras Epidemiol ; 23: e200004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130393

RESUMO

INTRODUCTION: Epidemiological studies have shown associations between placental measurements and perinatal and later life outcomes. OBJECTIVES: To report placental measurements and evaluate their association with birth weight in a Brazilian birth cohort. METHODS: Retrospective cohort study with 958 mothers, placentas, and newborns delivered at the Ribeirão Preto Medical School Hospital, Universidade de São Paulo, Brazil, in 2010 and 2011. The information was collected from interviews, medical records, and pathology reports. The placental measurements were: weight, largest and smallest diameters, eccentricity, thickness, shape, area, and birth weight/placental weight and placental weight/birth weight ratios. We analyzed the associations between birth weight and placental measurements using multiple linear regression. RESULTS: Placental weight alone accounted for 48% of birth weight variability (p < 0.001), whereas placental measurements combined (placental weight, largest and smallest diameters, and thickness) were responsible for 50% (p < 0.001). When adjusted for maternal and neonatal characteristics, placental measurements explained 74% of birth weight variability (p < 0.001). CONCLUSION: Placental measurements are powerful independent predictors of birth weight. Placental weight is the most predictive of them, followed by the smallest diameter.


Assuntos
Peso ao Nascer/fisiologia , Placenta/anatomia & histologia , Adulto , Índice de Massa Corporal , Brasil , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Análise Multivariada , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
J Korean Med Sci ; 35(10): e73, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32174066

RESUMO

BACKGROUND: Twin-to-twin transfusion syndrome (TTTS) is a serious complication of monochorionic twin pregnancies. It results from disproportionate blood supply to each fetus caused by abnormal vascular anastomosis within the placenta. Amniotic fluid (AF) is an indicator reflecting the various conditions of the fetus, and an imbalance in AF volume is essential for the antenatal diagnosis of TTTS by ultrasound. In this study, two different mass spectrometry quantitative approaches were performed to identify differentially expressed proteins (DEPs) within matched pairs of AF samples. METHODS: We characterized the AF proteome in pooled AF samples collected from donor and recipient twin pairs (n = 5 each) with TTTS by a global proteomics profiling approach and then preformed the statistical analysis to determine the DEPs between the two groups. Next, we carried out a targeted proteomic approach (multiple reaction monitoring) with DEPs to achieve high-confident TTTS-associated AF proteins. RESULTS: A total of 103 AF proteins that were significantly altered in their abundances between donor and recipient fetuses. The majority of upregulated proteins identified in the recipient twins (including carbonic anhydrase 1, fibrinogen alpha chain, aminopeptidase N, alpha-fetoprotein, fibrinogen gamma chain, and basement membrane-specific heparan sulfate proteoglycan core protein) have been associated with cardiac or dermatologic disease, which is often seen in recipient twins as a result of volume overload. In contrast, proteins significantly upregulated in AF collected from donor twins (including IgGFc-binding protein, apolipoprotein C-I, complement C1q subcomponent subunit B, apolipoprotein C-III, apolipoprotein A-II, decorin, alpha-2-macroglobulin, apolipoprotein A-I, and fibronectin) were those previously shown to be associated with inflammation, ischemic cardiovascular complications or renal disease. CONCLUSION: In this study, we identified proteomic biomarkers in AF collected from donor and recipient twins in pregnancies complicated by TTTS that appear to reflect underlying functional and pathophysiological challenges faced by each of the fetuses.


Assuntos
Líquido Amniótico/metabolismo , Transfusão Feto-Fetal/diagnóstico , Proteômica , Biomarcadores/metabolismo , Feminino , Humanos , Recém-Nascido , Placenta/metabolismo , Gravidez , Gravidez de Gêmeos , Diagnóstico Pré-Natal , Proteoma
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