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1.
Cancer Sci ; 111(1): 36-46, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31705593

RESUMEN

Osteosarcoma (OS) is a highly malignant bone tumor and the prognosis for non-responders to chemotherapy remains poor. Previous studies have shown that human sarcomas contain sarcoma-initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC-related genes, and tried to regulate the proliferation of OS by metabolic interference. Initially, we established a new human OS cell line (OS13) and isolated clones showing higher tumorigenesis as SIC (OSHIGH ) and counterpart clones. OSHIGH cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using RNA-sequencing, we identified LIN28B as a SIC-related gene highly expressed in OSHIGH cells. mRNA of LIN28B was expressed in sarcoma cell lines including OS13, but its expression was not detectable in normal organs other than the testis and placenta. LIN28B protein was also detected in various sarcoma tissues. Knockdown of LIN28B in OS13 cells reduced tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination therapy consisting of a glycolysis inhibitor and low-dose chemotherapy had antitumor effects. In conclusion, manipulation of glycolysis combined with chemotherapy might be a good adjuvant treatment for OS. Development of immunotherapy targeting LIN28B, a so-called cancer/testis antigen, might be a good approach.


Asunto(s)
Neoplasias Óseas/genética , Glucólisis/genética , Osteosarcoma/genética , Proteínas de Unión al ARN/genética , Animales , Neoplasias Óseas/patología , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Osteosarcoma/patología , Fosforilación Oxidativa , Placenta/patología , Embarazo , Pronóstico , ARN Mensajero/genética , Testículo/patología
3.
Eur J Histochem ; 63(4)2019 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-31833328

RESUMEN

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by interleukin (IL)-6 and IL-10 that generate nearly opposing responses. The suppressor of cytokine signaling 3 (SOCS3) is the negative regulator of STAT3 and plays an important role in the negative regulation of the inflammatory process. Evidence has shown the importance of STAT3 and SOCS3 during implantation and normal pregnancy. However, little is known about the relationship of both factors under hyperglycemic condition. The aim of this study was to evaluate the placenta regions exhibiting immunopositivity for STAT3 and SOCS3 in hyperglycemic rats, as well as correlate these proteins with IL-10 and IL-6 levels. It was observed increased expression of STAT3 at the labyrinth (approximately 47% of increase compared to control) and junctional zone (approximately 32% of increase compared to control) from hyperglycemic placentas. Similar results were observed to SOCS3 (approximately 71% -labyrinth- and 53% -junctional zone- of increase compared to control). The levels of IL-10 were augmented at hyperglycemic placentas (approximately 1.5 fold of increase) and they were positively correlated with the increase of STAT3 at the labyrinth and SOCS at junctional zone. Therefore, under hyperglycemic conditions, the relation between STAT3 and SOCS3 was changed, leading to unbalance of the cytokine profile.


Asunto(s)
Hiperglucemia/metabolismo , Placenta/metabolismo , Factor de Transcripción STAT3/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Animales , Anticuerpos/inmunología , Femenino , Cabras , Hiperglucemia/patología , Inmunohistoquímica , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Placenta/patología , Embarazo , Conejos , Ratas Wistar , Factor de Transcripción STAT3/inmunología , Proteína 3 Supresora de la Señalización de Citocinas/inmunología
4.
Pan Afr Med J ; 34: 56, 2019.
Artículo en Francés | MEDLINE | ID: mdl-31762922

RESUMEN

The examination of the placenta is part of the assessment of intrauterine growth retardation (IUGR). Its interest lies in retardation etiology research and in maternal-fetal consequences which can arise from it as well as in the implementation of preventive strategies for subsequent pregnancies in patients with recurrent diseases. We conducted a study of patients with severe IUGR monitored in the Department of Neonatology of the Ibn Sina University Hospital in Rabat in order to identify possible anatomopathological lesions in the placenta.


Asunto(s)
Retardo del Crecimiento Fetal/etiología , Enfermedades Placentarias/diagnóstico , Placenta/patología , Adulto , Femenino , Humanos , Enfermedades Placentarias/patología , Embarazo , Índice de Severidad de la Enfermedad
5.
Orv Hetil ; 160(48): 1894-1903, 2019 Dec.
Artículo en Húngaro | MEDLINE | ID: mdl-31760773

RESUMEN

Introduction: According to the Hungarian law, placental examination is not mandatory, although it is known from the international practice that it can give valuable information in cases of stillbirth or in conditions, where the neonate has difficulty in the postnatal adaptation. Aim: It can be useful in the early detection of diseases, which otherwise would have gone undetected until late in life. This article is unique in Hungary, as no similar guideline exists in Hungarian language. Method: The recommendation of the Royal College of Pathologists (United Kingdom) determines those conditions where essential information can be obtained from the placental examination in not normal pregnancies. It serves as a useful guide in the medical practice. The journal titled "Placenta", first published in 1980 with impact factor above two, just underlines this statement. Results: In this article, the authors present the recent guideline of the RCPath and finish with the presentation of established clinicopathological association that might help clinicians to get the most valuable information from placental examination. Conclusion: The present article aims to summarise updated recommendations and present clinicopathological correlations. Orv Hetil. 2019; 160(48): 1894-1903.


Asunto(s)
Placenta/patología , Guías de Práctica Clínica como Asunto , Mortinato , Femenino , Humanos , Hungría , Recién Nacido , Embarazo , Sociedades Médicas , Cordón Umbilical/patología , Reino Unido
6.
Nat Med ; 25(11): 1699-1705, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31686035

RESUMEN

Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF)1-3, its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos4. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis5,6, a high number of embryos containing abnormal cells can pass this strong selection barrier7,8. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages.


Asunto(s)
Inestabilidad Cromosómica/genética , Variaciones en el Número de Copia de ADN/genética , Desarrollo Embrionario/genética , Fertilización In Vitro/efectos adversos , Blastocisto/metabolismo , Linaje de la Célula/genética , Embrión de Mamíferos , Femenino , Feto , Genotipo , Humanos , Recién Nacido , Masculino , Placenta/metabolismo , Placenta/patología , Polimorfismo de Nucleótido Simple/genética , Embarazo
7.
Top Magn Reson Imaging ; 28(5): 285-297, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31592995

RESUMEN

The Human Placenta Project has focused attention on the need for noninvasive magnetic resonance imaging (MRI)-based techniques to diagnose and monitor placental function throughout pregnancy. The hope is that the management of placenta-related pathologies would be improved if physicians had more direct, real-time measures of placental health to guide clinical decision making. As oxygen alters signal intensity on MRI and oxygen transport is a key function of the placenta, many of the MRI methods under development are focused on quantifying oxygen transport or oxygen content of the placenta. For example, measurements from blood oxygen level-dependent imaging of the placenta during maternal hyperoxia correspond to outcomes in twin pregnancies, suggesting that some aspects of placental oxygen transport can be monitored by MRI. Additional methods are being developed to accurately quantify baseline placental oxygenation by MRI relaxometry. However, direct validation of placental MRI methods is challenging and therefore animal studies and ex vivo studies of human placentas are needed. Here we provide an overview of the current state of the art of oxygen transport and quantification with MRI. We suggest that as these techniques are being developed, increased focus be placed on ensuring they are robust and reliable across individuals and standardized to enable predictive diagnostic models to be generated from the data. The field is still several years away from establishing the clinical benefit of monitoring placental function in real time with MRI, but the promise of individual personalized diagnosis and monitoring of placental disease in real time continues to motivate this effort.


Asunto(s)
Hiperoxia/diagnóstico por imagen , Hiperoxia/patología , Imagen por Resonancia Magnética/métodos , Oxígeno/sangre , Placenta/diagnóstico por imagen , Placenta/patología , Animales , Femenino , Humanos , Embarazo
8.
Nat Commun ; 10(1): 3866, 2019 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-31530803

RESUMEN

Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 104 (0.66 × 104) and 2.09 × 104 (0.9 × 104) particles per mm3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers' residential BC exposure during pregnancy (0.63-2.42 µg per m3). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards.


Asunto(s)
Contaminantes Atmosféricos/metabolismo , Exposición Materna/efectos adversos , Intercambio Materno-Fetal , Placenta/metabolismo , Hollín/metabolismo , Contaminantes Atmosféricos/toxicidad , Bélgica , Biopsia , Estudios de Cohortes , Ecotoxicología , Femenino , Humanos , Microscopía Electrónica de Transmisión , Permeabilidad , Placenta/patología , Placenta/ultraestructura , Embarazo , Características de la Residencia/estadística & datos numéricos , Hollín/análisis , Hollín/toxicidad
9.
Arkh Patol ; 81(4): 39-42, 2019.
Artículo en Ruso | MEDLINE | ID: mdl-31407716

RESUMEN

OBJECTIVE: To study placental morphometric parameters in women who have experienced mono- and mixed viral respiratory infections during pregnancy. SUBJECT AND METHODS: Three groups of placentas were studied. Group 1 consisted of 25 placentas from women with physiological pregnancy; Group 2 included 25 placentas from those who had experienced parainfluenza type 3; and Group 3 comprised 25 placentas from those who had mixed respiratory viral infection (parainfluenza type 3 concurrent with influenza A (H3N2)) in the second trimester of pregnancy. The weight of the placenta and its morphometric parameters were determined on hematoxylin and eosin stained tissue sections using a square multifaceted stereometric grid placed in the microscopic eyepiece (magnification 15×20). RESULTS: Group 3 versus Group 2 exhibited a reduction in placental weights along with an increase in the stroma, fibrinoid around the villi and in the stroma, pseudonecroses, calcification, intermediate immature villi, small avascular villi, and hemorrhages in the intervillous space and a decrease the volume of the circulatory bed. CONCLUSION: In women in the second trimester of pregnancy, mixed viral respiratory infection has a more pronounced negative impact on the formation of the placenta.


Asunto(s)
Placenta , Complicaciones Infecciosas del Embarazo , Infecciones del Sistema Respiratorio , Femenino , Humanos , Subtipo H3N2 del Virus de la Influenza A , Placenta/patología , Embarazo , Complicaciones Infecciosas del Embarazo/patología , Infecciones del Sistema Respiratorio/complicaciones
10.
Arkh Patol ; 81(4): 43-47, 2019.
Artículo en Ruso | MEDLINE | ID: mdl-31407717

RESUMEN

OBJECTIVE: To study a change in the architectonics of fetal surface veins of the placenta and the structure of the latter in cytomegalovirus infection in pregnant women. MATERIAL AND METHODS: Placentas were studied and divided in 3 groups: 1) 35 placentas from women with physiological pregnancy; 2) 37 placentas from women with an exacerbation of latent cytomegalovirus infection and with chronic compensated placental insufficiency; 3) 30 placentas from those with an exacerbation of latent cytomegalovirus infection and with chronic subcompensated placental insufficiency. After X-ray contrasting the fetal surface veins of the placenta and collecting its sections for morphological analysis, the changes in the blood vessels were compared with the structure of the villous chorion. RESULTS: As compared with Group 2, Group 3 showed reductions in placental weights and placental areas, as well as cotyledon asymmetry and a preponderance of anatomical forms with weak vascular contrasting along with the more frequent emergence of areas of varicosity, contraction, and inflammation of the umbilical vein, as well as the placental fetal surface veins. The investigators more often detected collagenization, fibrinoid degradation, and the increased stromal volume of the stem villi, fibrinoid deposition around the latter, and decreases in the proportion of the intervillous space and syncytiotrophoblast; dilatation of the veins and narrowing of the arteries of the stem villi; pronounced plethora of terminal villi and their avascular forms, intermediate immature villi, chorioamnionitis, deciduitis, pseudonecrosis, calcifications, as well as hemorrhages in the intervillous space. CONCLUSION: In the development of subcompensated placental insufficiency in women who have experienced an exacerbation of latent cytomegalovirus infection in the second trimester of pregnancy, an important role is assigned to anatomical and pathological changes in the umbilical, fetal surface, and villous chorionic veins, which indicate the development of fetoplacental hypertension, the deceleration of blood flow, and the longer contact of the pathogen with the endothelium and syncytiotrophoblast.


Asunto(s)
Infecciones por Citomegalovirus , Placenta , Insuficiencia Placentaria , Complicaciones Infecciosas del Embarazo , Corion , Infecciones por Citomegalovirus/complicaciones , Femenino , Humanos , Placenta/irrigación sanguínea , Placenta/patología , Insuficiencia Placentaria/virología , Embarazo , Complicaciones Infecciosas del Embarazo/patología , Segundo Trimestre del Embarazo
11.
Exp Parasitol ; 205: 107736, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31442455

RESUMEN

Goats are frequently described as an intermediate host for the protozoan Neospora caninum, manifesting the disease mainly by recurrent abortions with placentitis and encephalitis in fetuses. Several reports of natural and experimental infections in cattle and mice show differences in the immune response, and the outcome of the infection can be variable depending on the species affected and by the behavior of the infective strain. This study describes for the first time two Neospora caninum strains isolated from naturally infected goats from the state of Minas Gerais, Brazil. One placenta and one brain from different goats were processed for a first bioassay in gerbils (Meriones unguiculatus). Subsequently, a second bioassay was performed by inoculating the processed brain samples from gerbils into Interferon gamma (IFN-γ) knockout mice (KO mice). Tachyzoites collected from the peritoneal fluid of the KO mice were inoculated into VERO cell monolayers, where they presented a very slow growth rate. The tachyzoites were also inoculated into BALB/c mice with a dose of 106 tachyzoites per animal. After a 5-week follow up, the animals infected with both of the strains developed a strong polarized Th1 response with increased serum and spleen gene expression levels of pro-inflammatory cytokines (mainly IFN-γ and TNF-α) in the first week. Tissue lesions were mild in the animals infected with both strains. Despite the strong immune response preventing an infection in the visceral organs, the parasite was able to reach the brain, causing progressive brain lesions from the second to fifth week post infection. The NC-goat1-infected mice presented with severe meningoencephalitis, but the NC-goat2-infected animals had considerable histological brain lesions only at week 5. Immunohistochemical analysis of the mouse brains revealed a different pattern of inflammatory cells compared to the naturally infected goats. A severe inflammatory infiltrate of CD3+ T lymphocytes was found in the NC-goat1-infected mice. A more discrete infiltrate of CD3+ T cells was found in the NC-goat2-infected animals. Additionally, IBA1 IHC revealed an intense microglial reaction and monocyte perivascular cuffs in the NC-goat1-infected animals and lower microglia/monocyte infiltrates in the NC-goat2-infected mice. This work contributes knowledge on the pathogenicity of new Neospora caninum strains in mice, comparable with other well-established mouse models of the disease, and demonstrates the importance of studying goats as an intermediate host of this parasite.


Asunto(s)
Coccidiosis/veterinaria , Enfermedades de las Cabras/parasitología , Neospora/patogenicidad , Animales , Bioensayo/veterinaria , Encéfalo/parasitología , Encéfalo/patología , Coccidiosis/parasitología , Coccidiosis/patología , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica , Gerbillinae , Enfermedades de las Cabras/patología , Cabras , Inmunohistoquímica/veterinaria , Interferón gamma/genética , Interferón gamma/metabolismo , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Neospora/aislamiento & purificación , Páncreas/patología , Placenta/patología , Embarazo , Bazo/metabolismo , Bazo/patología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Células Vero
12.
Eur Radiol ; 29(11): 6152-6162, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31444599

RESUMEN

OBJECTIVE: The aim of this study was to investigate whether intraplacental texture features from routine placental MRI can objectively and accurately predict invasive placentation. MATERIAL AND METHODS: This retrospective study includes 99 pregnant women with pathologically confirmed placental invasion and 56 pregnant women with simple placenta previa. All participants underwent magnetic resonance imaging after 24 gestational weeks. The placenta was segmented in sagittal images from both turbo spin echo (TSE) and balanced turbo field echo (bTFE) sequences. Textural features were extracted from the both original and Laplacian of Gaussian (LoG)-filtered MRI images. An automated machine learning algorithm was applied to the extracted feature sets to obtain the optimal preprocessing steps, classification algorithm, and corresponding hyper-parameters. RESULTS: A gradient boosting classifier using all textual features from original and LoG-filtered TSE images and bTFE images identified by the automated machine learning algorithm achieved the optimal performance with sensitivity, specificity, accuracy, and area under ROC curve (AUC) of 100%, 88.5%, 95.2%, and 0.98 in the prediction of placental invasion. In addition, textural features that contributed to the prediction of placental invasion differ from the features significantly affected by normal placenta maturation. CONCLUSIONS: Quantifying intraplacental heterogeneity using LoG filtration and texture analysis highlights the different heterogeneous appearance caused by abnormal placentation relative to normal maturation. The predictive model derived from automated machine learning yielded good performance, indicating the proposed radiomic analysis pipeline can accurately predict placental invasion and facilitate clinical decision-making for pregnant women with suspicious placental invasion. KEY POINTS: • The intraplacental texture features have high efficiency in prediction of invasive placentation after 24 gestational weeks. • The features with dominated predictive power did not overlap with the features significantly affected by gestational age.


Asunto(s)
Algoritmos , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , Placenta Previa/diagnóstico , Placenta/patología , Placentación/fisiología , Diagnóstico Prenatal/métodos , Adulto , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Adulto Joven
13.
Handb Clin Neurol ; 162: 57-66, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31324328

RESUMEN

Examination of the placenta provides a unique opportunity to explore and understand the intrauterine environment, as well as providing a record of events that may be associated with adverse pregnancy outcomes, one of the most devastating of which is central nervous system (CNS) injury. A number of placental lesions have been described in association with various forms of neurologic injury. They can be divided into four major categories: sentinel events, inflammatory lesions, vascular lesions, and "biomarker" lesions, which are not themselves causative, but are often found in association with other lesions that are causative. The purpose of this review is to outline these placental lesions and summarize the types of CNS injury that have been described in association with each. Finally, one of the most important of all risk factors for CNS injury is the finding of multiple independent placental lesions. The effects of these lesions may be synergistic, particularly when metachronous, with an earlier lesion leaving the CNS more vulnerable to the effects of a later lesion.


Asunto(s)
Enfermedades del Sistema Nervioso Central/patología , Placenta/patología , Adulto , Animales , Causalidad , Enfermedades del Sistema Nervioso Central/congénito , Enfermedades del Sistema Nervioso Central/etiología , Femenino , Enfermedades Fetales/patología , Humanos , Recién Nacido , Embarazo
14.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-31269775

RESUMEN

Maternal uterine artery blood flow is critical to maintaining the intrauterine environment, permitting normal placental function, and supporting fetal growth. It has long been believed that inadequate transformation of the maternal uterine vasculature is a consequence of primary defective trophoblast invasion and leads to the development of preeclampsia. That early pregnancy maternal uterine artery perfusion is strongly associated with placental cellular function and behaviour has always been interpreted in this context. Consistently observed changes in pre-conceptual maternal and uterine artery blood flow, abdominal pregnancy implantation, and late pregnancy have been challenging this concept, and suggest that abnormal placental perfusion may result in trophoblast impairment, rather than the other way round. This review focuses on evidence that maternal cardiovascular function plays a significant role in the pathophysiology of preeclampsia.


Asunto(s)
Preeclampsia/fisiopatología , Trofoblastos/patología , Arteria Uterina/fisiopatología , Animales , Velocidad del Flujo Sanguíneo , Comunicación Celular , Movimiento Celular , Femenino , Humanos , Estrés Oxidativo , Placenta/irrigación sanguínea , Placenta/metabolismo , Placenta/patología , Placenta/fisiopatología , Preeclampsia/metabolismo , Preeclampsia/patología , Embarazo , Trofoblastos/metabolismo , Arteria Uterina/metabolismo , Arteria Uterina/patología , Resistencia Vascular
15.
Hypertens Pregnancy ; 38(3): 176-183, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31271326

RESUMEN

Objective: We aimed to determine whether abnormal coagulation laboratory testing results in preeclampsia, are associated with adverse pregnancy outcomes and placental histopathology lesions. Methods: Demographic, labor, laboratory-testing, and placental histopathology reports of pregnancies complicated by preeclampsia were compared between those with and without abnormal coagulation profile (ACP). Results: Of 348 cases of preeclampsia 16.1% had ACP. There were no differences between the groups in GA at delivery, severe features, placental-abruption, SGA, composite adverse neonatal outcome and placental histopathology lesions. Conclusion: ACP in pregnancies complicated by preeclampsia was not associated with any of the studied outcomes. Our data question the usefulness of routine coagulation tests in the initial assessment of women presenting with preeclampsia.


Asunto(s)
Coagulación Sanguínea/fisiología , Placenta/patología , Preeclampsia/sangre , Adulto , Pruebas de Coagulación Sanguínea , Femenino , Humanos , Recién Nacido Pequeño para la Edad Gestacional , Preeclampsia/patología , Embarazo , Resultado del Embarazo , Adulto Joven
16.
Medicine (Baltimore) ; 98(26): e16166, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31261546

RESUMEN

RATIONALE: The placenta membranacea (PM) is a rare type of placental abnormality, which is associated with placenta previa, antepartum hemorrhage (APH), postpartum hemorrhage (PPH), chorioamnionitis, fetal growth restriction (FGR), preterm birth even stillbirth. The purpose of this case report is to summarize the characteristics and analyze the relevant factors of PM. PATIENTS CONCERNS: Repetitive B-ultrasound of the first patient demonstrated a thin placenta covering the most part of uterine wall, which completely covers the internal cervical ostium for 22 weeks. B-ultrasound of the second patient showed placenta partially covering the internal cervical ostium and fetus small for gestation age for 23 days. The third patient complained of abdominal pain and vaginal discharge for 1 day. DIAGNOSES: Diagnosis of PM is based on Doppler ultrasound apparatus, and confirmed by pathology. INTERVENTIONS AND OUTCOMES: In the first patient, elective cesarean section was performed. The second patient required termination of pregnancy due to poor postnatal outcome. The third patient underwent intrauterine fetal death. Of these 3 cases, one delivered a term fetus by cesarean section complicated with placenta previa and placenta accreta, one terminated the pregnancy because of serious fetal growth retardation, and the other underwent intrauterine fetal death. LESSONS: High-resolution color Doppler ultrasound apparatus can improve the diagnostic accuracy, and close antenatal surveillance followed by proper arrangement of delivery may improve neonatal outcomes.


Asunto(s)
Placenta/anomalías , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Placenta/diagnóstico por imagen , Placenta/patología , Embarazo , Resultado del Embarazo , Ultrasonografía Doppler en Color , Ultrasonografía Prenatal , Adulto Joven
17.
BMC Cancer ; 19(1): 744, 2019 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-31357948

RESUMEN

BACKGROUND: Gestational choriocarcinoma is a rare malignancy believed to arise from the trophoblast cells of the placenta. Despite the frequently aggressive clinical nature, choriocarcinoma has been routinely curable with cytotoxic chemotherapy for over 50 years. To date little is known regarding the route to oncogenesis in this malignancy. METHODS: In a case of intraplacental choriocarcinoma, we have performed detailed genetic studies including microsatellite analysis, whole genome sequencing (WGS) and methylation analysis of the tumour and surrounding mature placenta. RESULTS: The results of the WGS sequencing indicated a very low level of mutation and the absence of any driver mutations or oncogene activity in the tumour. The methylation analysis identified a distinctly different profile in the tumour from that of the mature placenta. Comparison with a panel of reference methylation profiles from different stages of placental development indicated that the tumour segregated with the first trimester samples. CONCLUSIONS: These findings suggest that gestational choriocarcinoma is likely to arise as a result of aberrations of methylation during development, rather than from DNA mutations. The results support the hypothesis that gestational choriocarcinoma arises from a normally transient early trophoblast cell. At this point in development this cell naturally has a phenotype of rapid division, tissue invasion and sensitivity to DNA damaging chemotherapy that is very similar to that of the mature choriocarcinoma cell.


Asunto(s)
Coriocarcinoma/genética , Metilación de ADN/genética , Enfermedad Trofoblástica Gestacional/genética , Mutación/genética , Placenta/patología , Neoplasias Uterinas/genética , Adulto , Islas de CpG/genética , Epigénesis Genética/genética , Femenino , Estudios de Seguimiento , Humanos , Repeticiones de Microsatélite/genética , Fenotipo , Embarazo , Trofoblastos/patología , Secuenciación Completa del Genoma
18.
PLoS Genet ; 15(6): e1008107, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31194736

RESUMEN

Spontaneous preterm birth (SPTB) is the leading cause of neonatal death and morbidity worldwide. Both maternal and fetal genetic factors likely contribute to SPTB. We performed a genome-wide association study (GWAS) on a population of Finnish origin that included 247 infants with SPTB (gestational age [GA] < 36 weeks) and 419 term controls (GA 38-41 weeks). The strongest signal came within the gene encoding slit guidance ligand 2 (SLIT2; rs116461311, minor allele frequency 0.05, p = 1.6×10-6). Pathway analysis revealed the top-ranking pathway was axon guidance, which includes SLIT2. In 172 very preterm-born infants (GA <32 weeks), rs116461311 was clearly overrepresented (odds ratio 4.06, p = 1.55×10-7). SLIT2 variants were associated with SPTB in another European population that comprised 260 very preterm infants and 9,630 controls. To gain functional insight, we used immunohistochemistry to visualize SLIT2 and its receptor ROBO1 in placentas from spontaneous preterm and term births. Both SLIT2 and ROBO1 were located in villous and decidual trophoblasts of embryonic origin. Based on qRT-PCR, the mRNA levels of SLIT2 and ROBO1 were higher in the basal plate of SPTB placentas compared to those from term or elective preterm deliveries. In addition, in spontaneous term and preterm births, placental SLIT2 expression was correlated with variations in fetal growth. Knockdown of ROBO1 in trophoblast-derived HTR8/SVneo cells by siRNA indicated that it regulate expression of several pregnancy-specific beta-1-glycoprotein (PSG) genes and genes involved in inflammation. Our results show that the fetal SLIT2 variant and both SLIT2 and ROBO1 expression in placenta and trophoblast cells may be correlated with susceptibility to SPTB. SLIT2-ROBO1 signaling was linked with regulation of genes involved in inflammation, PSG genes, decidualization and fetal growth. We propose that this receptor-ligand couple is a component of the signaling network that promotes SPTB.


Asunto(s)
Desarrollo Fetal/genética , Predisposición Genética a la Enfermedad , Péptidos y Proteínas de Señalización Intercelular/genética , Proteínas del Tejido Nervioso/genética , Nacimiento Prematuro/genética , Receptores Inmunológicos/genética , Femenino , Feto , Finlandia , Regulación de la Expresión Génica/genética , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Placenta/patología , Polimorfismo de Nucleótido Simple , Embarazo , Glicoproteínas beta 1 Específicas del Embarazo/genética , Nacimiento Prematuro/patología , Transducción de Señal , Trofoblastos/patología
19.
Cancer Immunol Immunother ; 68(7): 1039-1058, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31165204

RESUMEN

The emergence of immunotherapy has revolutionized medical oncology with unprecedented advances in cancer treatment over the past two decades. However, a major obstacle in cancer immunotherapy is identifying appropriate tumor-specific antigens to make targeted therapy achievable with fewer normal cells being impaired. The similarity between placentation and tumor development and growth has inspired many investigators to discover antigens for effective immunotherapy of cancers. Placenta-specific 1 (PLAC1) is one of the recently discovered placental antigens with limited normal tissue expression and fundamental roles in placental function and development. There is a growing body of evidence showing that PLAC1 is frequently activated in a wide variety of cancer types and promotes cancer progression. Based on the restricted expression of PLAC1 in testis, placenta and a wide variety of cancers, we have designated this molecule with new terminology, cancer-testis-placenta (CTP) antigen, a feature that PLAC1 shares with many other cancer testis antigens. Recent reports from our lab provide compelling evidence on the preferential expression of PLAC1 in prostate cancer and its potential utility in prostate cancer immunotherapy. PLAC1 may be regarded as a potential CTP antigen for targeted cancer immunotherapy based on the available data on its promoting function in cancer development and also its expression in cancers of different histological origin. In this review, we will summarize current data on PLAC1 with emphasis on its association with cancer development and immunotherapy.


Asunto(s)
Antígenos de Neoplasias/inmunología , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Neoplasias/terapia , Proteínas Gestacionales/antagonistas & inhibidores , Antígenos de Neoplasias/metabolismo , Antineoplásicos Inmunológicos/farmacología , Biomarcadores de Tumor/inmunología , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Inmunoterapia/métodos , Masculino , Terapia Molecular Dirigida/métodos , Neoplasias/inmunología , Neoplasias/patología , Placenta/patología , Embarazo , Proteínas Gestacionales/inmunología , Proteínas Gestacionales/metabolismo , Testículo/patología
20.
EBioMedicine ; 44: 639-655, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31160271

RESUMEN

BACKGROUND: Malaria infection in pregnancy is a major cause of maternal and foetal morbidity and mortality worldwide. Mouse models for gestational malaria allow for the exploration of the mechanisms linking maternal malaria infection and poor pregnancy outcomes in a tractable model system. The composition of the gut microbiota has been shown to influence susceptibility to malaria infection in inbred virgin mice. In this study, we explore the ability of the gut microbiota to modulate malaria infection severity in pregnant outbred Swiss Webster mice. METHODS: In Swiss Webster mice, the composition of the gut microbiota was altered by disrupting the native gut microbes through broad-spectrum antibiotic treatment, followed by the administration of a faecal microbiota transplant derived from mice possessing gut microbes reported previously to confer susceptibility or resistance to malaria. Female mice were infected with P. chabaudi chabaudi AS in early gestation, and the progression of infection and pregnancy were tracked throughout gestation. To assess the impact of maternal infection on foetal outcomes, dams were sacrificed at term to assess foetal size and viability. Alternatively, pups were delivered by caesarean section and fostered to assess neonatal survival and pre-weaning growth in the absence of maternal morbidity. A group of dams was also euthanized at mid-gestation to assess infection and pregnancy outcomes. FINDINGS: Susceptibility to infection varied significantly as a function of source of transplanted gut microbes. Parasite burden was negatively correlated with the abundance of five specific OTUs, including Akkermansia muciniphila and OTUs classified as Allobaculum, Lactobacillus, and S24-7 species. Reduced parasite burden was associated with reduced maternal morbidity and improved pregnancy outcomes. Pups produced by dams with high parasite burdens displayed a significant reduction in survival in the first days of life relative to those from malaria-resistant dams when placed with foster dams. At midgestation, plasma cytokine levels were similar across all groups, but expression of IFNγ in the conceptus was elevated in infected dams, and IL-10 only in susceptible dams. In the latter, transcriptional and microscopic evidence of monocytic infiltration was observed with high density infection; likewise, accumulation of malaria haemozoin was enhanced in this group. These responses, combined with reduced vascularization of the placenta in this group, may contribute to poor pregnancy outcomes. Thus, high maternal parasite burden and associated maternal responses, potentially dictated by the gut microbial community, negatively impacts term foetal health and survival in the early postnatal period. INTERPRETATION: The composition of the gut microbiota in Plasmodium chabaudi chabaudi AS-infected pregnant Swiss Webster mice transcends the outbred genetics of the Swiss Webster mouse stock as a determinant of malaria infection severity, subsequently influencing pregnancy outcomes in malaria-exposed progeny. FUND: Research reported in this manuscript was supported by the University of Florida College of Veterinary Medicine (JMM, MM, and MG), the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award numbers T32AI060546 (to CDMS), R01HD46860 and R21AI111242 (to JMM), and R01 DK109560 (to MM). MG was supported by Department of Infectious Diseases and Immunology and University of Florida graduate assistantships. AA was supported by the 2017-2019 Peach State LSAMP Bridge to the Doctorate Program at the University of Georgia (National Science Foundation, Award # 1702361). The content is solely the responsibility of the authors and does not necessarily represent official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, or the National Institutes of Health.


Asunto(s)
Susceptibilidad a Enfermedades , Microbioma Gastrointestinal , Predisposición Genética a la Enfermedad , Malaria/diagnóstico , Malaria/etiología , Complicaciones Parasitarias del Embarazo , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Terapia Combinada , Citocinas/metabolismo , Modelos Animales de Enfermedad , Trasplante de Microbiota Fecal , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Malaria/terapia , Ratones , Placenta/efectos de los fármacos , Placenta/parasitología , Placenta/patología , Embarazo , Resultado del Embarazo , Pronóstico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
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