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1.
Exp Parasitol ; 205: 107736, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442455

RESUMO

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.


Assuntos
Coccidiose/veterinária , Doenças das Cabras/parasitologia , Neospora/patogenicidade , Animais , Bioensaio/veterinária , Encéfalo/parasitologia , Encéfalo/patologia , Cercopithecus aethiops , Coccidiose/parasitologia , Coccidiose/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Gerbillinae , Doenças das Cabras/patologia , Cabras , Imuno-Histoquímica/veterinária , Interferon gama/genética , Interferon gama/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neospora/isolamento & purificação , Pâncreas/patologia , Placenta/patologia , Gravidez , Baço/metabolismo , Baço/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Células Vero
2.
Arkh Patol ; 81(4): 39-42, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31407716

RESUMO

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.


Assuntos
Placenta , Complicações Infecciosas na Gravidez , Infecções Respiratórias , Feminino , Humanos , Vírus da Influenza A Subtipo H3N2 , Placenta/patologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Infecções Respiratórias/complicações
3.
Arkh Patol ; 81(4): 43-47, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31407717

RESUMO

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.


Assuntos
Infecções por Citomegalovirus , Placenta , Insuficiência Placentária , Complicações Infecciosas na Gravidez , Córion , Infecções por Citomegalovirus/complicações , Feminino , Humanos , Placenta/irrigação sanguínea , Placenta/patologia , Insuficiência Placentária/virologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Segundo Trimestre da Gravidez
4.
Medicine (Baltimore) ; 98(26): e16166, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261546

RESUMO

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.


Assuntos
Placenta/anormalidades , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Placenta/diagnóstico por imagem , Placenta/patologia , Gravidez , Resultado da Gravidez , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal , Adulto Jovem
5.
Food Chem Toxicol ; 131: 110538, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31152790

RESUMO

Dioscorea hispida var. daemona (Roxb) Prain & Burkill (DH), also known a tropical yam or intoxicating yam is a bitter wild tuber which is consumed as a staple food and traditionally used as a remedy in Malaysia. However, DH is also notorious for its intoxicating effects and there is currently a dearth of study of possible effects of DH on liver and placental tissues and hence its safe consumption warrants in-depth investigation. This study was therefore designed to investigate into the effect of DH on liver and placenta of pregnant rat via histopathological examination. Thirty pregnant Sprague-Dawley rats were randomly divided into five groups consisting of a control (distilled water) and four DH aqueous extract groups (250, 500, 1000 and 2000 mg/kg body weight). The extracts were administered via oral gavage daily throughout the study and animals were sacrificed on day 21. Paraffin-embedded, hematoxylin and eosin stained sections of placenta and liver were examined. Significant changes (p < 0.05) were observed on relative liver and placental weights of animals treated with 2000 mg/kg body weight DH extract. The placental numbers were decreased with the increased of DH extract concentration. Liver histological examination in all treated groups showed that tissues underwent degeneration characterized by hepatocyte swelling, cytoplasmic vacuolation, cytolysis, margination and clumping of nucleus chromatin. Changes of the basal and labyrinth zone were observed in placental tissues in all treated groups. Glycogen cells were reduced with fibrin deposition in the basal zone, while irregular vessel formation was demonstrated in the labyrinth zone. UHPLC-ESI-MS analysis showed the presence four steroidal saponins DH. In conclusion, DH aqueous extract exert hepatotoxicity and adverse effects on the placenta of rats. However, the underlying mechanism and phytochemicals inducing the observed toxicity require further investigation.


Assuntos
Dioscorea/química , Fígado/efeitos dos fármacos , Placenta/efeitos dos fármacos , Extratos Vegetais/toxicidade , Plantas Medicinais/química , Administração Oral , Animais , Feminino , Fígado/patologia , Tamanho do Órgão/efeitos dos fármacos , Placenta/patologia , Extratos Vegetais/administração & dosagem , Gravidez , Ratos Sprague-Dawley
6.
J Vet Diagn Invest ; 31(4): 634-639, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31179891

RESUMO

A cluster of 4 bovine abortions caused by Coxiella burnetii occurred in a dairy herd in Uruguay during a 2-mo period. Case 1 consisted of a placenta from an aborted cow; cases 2-4 were fetuses and their placentas. Grossly, the placenta from one aborted cow had moderate, diffuse reddening of the cotyledons and loss of translucency of the intercotyledonary areas. No gross lesions were observed in the other 3 placentas. Microscopically, 2 of 4 placentas had fibrinonecrotizing placentitis with abundant intratrophoblastic gram-negative coccobacilli. C. burnetii was identified intralesionally by immunohistochemistry (IHC) in all 4 placentas, and by PCR and DNA sequencing in 3 placentas analyzed by these techniques. One fetus had mild neutrophilic alveolitis with multinucleate syncytial cells; no gross or microscopic lesions were observed in the other 2 fetuses examined. The lungs of the 3 fetuses were negative for C. burnetii by IHC. Tests performed to investigate other possible causes of abortions in the 4 cases were negative. C. burnetii causes Q fever in humans and coxiellosis in animals. Clusters of abortions in cattle by C. burnetii have not been reported previously, to our knowledge; this bacterium has been considered an opportunistic pathogen associated only with sporadic abortion in cattle. We present herein a cluster of 4 bovine abortions caused by C. burnetii in a dairy farm during a period of 2 mo and a review of the literature on C. burnetii infection in cattle.


Assuntos
Aborto Animal/microbiologia , Doenças dos Bovinos/microbiologia , Coxiella burnetii/isolamento & purificação , Complicações Infecciosas na Gravidez/veterinária , Febre Q/veterinária , Aborto Animal/epidemiologia , Animais , Bovinos , Coxiella burnetii/genética , Feminino , Feto/microbiologia , Feto/patologia , Humanos , Imuno-Histoquímica , Placenta/microbiologia , Placenta/patologia , Reação em Cadeia da Polimerase/veterinária , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/microbiologia , Febre Q/complicações , Febre Q/epidemiologia , Febre Q/microbiologia , Uruguai/epidemiologia
7.
Virchows Arch ; 475(3): 357-364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31218404

RESUMO

Chronic intervillositis of unknown etiology (CIUE) is a rare placental lesion associated with infiltration of mononuclear inflammatory cells into the intervillous space, poor perinatal outcomes (intrauterine fetal demise or fetal growth restriction), and high rates of recurrence. CD39 is the ectonucleotidase that protects tissues from inflammatory stress and cell injury, which is localized on the surface of villi in normal placentas; however, its expression and role in CIUE are unknown. The aims of this retrospective study were to determine the expression of CD39 in CIUE and its significance in pregnancy outcomes. We compared the number of CD68- and CD3-positive cells, CD39 expression, and complement 4d (C4d) and fibrin deposition in placental tissues from patients with CIUE (n = 22) and gestational age-matched controls (n = 20), and between CIUE pregnancies with poor and good outcomes. The numbers of CD68- or CD3-positive cells were significantly higher (P < 0.0001), whereas CD39 expression on the surface of villi and endothelial cells of the stem villi was significantly lower in the CIUE group than that in controls (45% vs. 95%, P < 0.0001 and 77% vs. 96%, P < 0.001, respectively). C4d and fibrin deposition were also significantly increased in CIUE compared with those of controls. Furthermore, CD39 downregulation and the number of CD68 cells were strongly associated with poor pregnancy outcomes (P < 0.01 and P < 0.05, respectively), but other histological parameters (CD3, C4d, and fibrin) did not show this association. Our study suggests that CD39 downregulation is a useful marker of CIUE and is associated with poor pregnancy outcomes in patients with CIUE.


Assuntos
Apirase/metabolismo , Doenças Placentárias/patologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Apirase/fisiologia , Complexo CD3/análise , Vilosidades Coriônicas/patologia , Regulação para Baixo , Células Endoteliais/patologia , Feminino , Retardo do Crescimento Fetal/patologia , Humanos , Placenta/patologia , Doenças Placentárias/metabolismo , Gravidez , Resultado da Gravidez/epidemiologia , Recidiva , Estudos Retrospectivos
8.
Cancer Immunol Immunother ; 68(7): 1039-1058, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165204

RESUMO

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.


Assuntos
Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias/terapia , Proteínas da Gravidez/antagonistas & inibidores , Antígenos de Neoplasias/metabolismo , Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Feminino , Humanos , Imunoterapia/métodos , Masculino , Terapia de Alvo Molecular/métodos , Neoplasias/imunologia , Neoplasias/patologia , Placenta/patologia , Gravidez , Proteínas da Gravidez/imunologia , Proteínas da Gravidez/metabolismo , Testículo/patologia
9.
Curr Med Sci ; 39(2): 190-195, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016509

RESUMO

Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide. No effective treatments to reduce its incidence and severity in clinical practice are currently available. A variety of hypotheses have been generated aiming to explain the origins of PE, notably being the genetic predispositions and placental dysfunction. As regard to placental dysfunction, much progress has been made in basic research and several potential therapeutic targets have been identified. This review will discuss in detail the potential therapeutic targets in PE models including uteroplacental blood flow, oxidative stress, vasoactive factors and inflammation/immune response, and introduce the evolving technologies for placental research nowadays.


Assuntos
Placenta/patologia , Pré-Eclâmpsia/etiologia , Animais , Feminino , Humanos , Inflamação/etiologia , Inflamação/genética , Estresse Oxidativo/genética , Pré-Eclâmpsia/genética , Gravidez
10.
Int J Infect Dis ; 84: 54-65, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31028878

RESUMO

A novel conceptual framework to describe the relationship between placental malaria and adverse infant neurodevelopmental outcomes is proposed. This conceptual framework includes three distinct stages: (1) maternal and environmental risk factors for the development of placental malaria; (2) placental pathology and inflammation associated with placental malaria infection; and (3) postnatal impacts of placental malaria. The direct, indirect, and bidirectional effects of these risk factors on infant neurodevelopment across the three stages were critically examined. These factors ultimately culminate in an infant phenotype that not only leads to adverse birth outcomes, but also to increased risks of neurological, cognitive, and behavioural deficits that may impact the quality of life in this high-risk population. Multiple risk factors were identified in this conceptual framework; nonetheless, based on current evidence, a key knowledge gap is the uncertainty regarding which are the most important and how exactly they interact.


Assuntos
Malária/complicações , Transtornos do Neurodesenvolvimento/etiologia , Doenças Placentárias/parasitologia , Complicações Parasitárias na Gravidez , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/complicações , Placenta/parasitologia , Placenta/patologia , Doenças Placentárias/patologia , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Qualidade de Vida , Fatores de Risco
11.
Infect Dis Obstet Gynecol ; 2019: 2094560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30940990

RESUMO

Background: Malaria during pregnancy may threaten the mother's health and cause serious structural damage to the internal architecture of the placenta, which subsequently affects the pregnancy outcome. A better understanding of the impact of malaria parasites on the placenta morphology is crucial for better management of pregnant women and their babies. Aim: To assess by stereology the histomorphology of selected placental structures in placenta malaria compared with normal placentae at term. Method: A total of 10 placentae comprising 5 controls and 5 cases were selected from 50 placentae that were collected at term (38 weeks ± 2 weeks) from the maternal delivery suit of Korle-Bu Teaching Hospital in Accra, Ghana. Blood from the placentae was collected for both rapid diagnostic test and microscopic examinations. Samples collected were examined for Plasmodium parasites, after which they were classified as study group (Plasmodium positive) or control (Plasmodium negative). Stereological quantification using systematic uniform random sampling technique with test point and intersection counting of photomicrographs were employed to estimate the mean volume densities of syncytial knots, syncytial necrosis, foetal capillaries, and intervillous spaces of the placentae on a total of 1,600 photomicrographs. Results: Out of the fifty placental samples from the maternal side tested for Plasmodium, six representing 12% were found to be infected with the parasite by both rapid diagnostic test and microscopy. On stereological assessment, the mean volume density of syncytial knots was significantly higher in the placental malaria group compared with the control placentae at term (P = 0.0080), but foetal capillaries (P = 0.7813), intervillous spaces (P = 0.8078), and syncytial necrosis (P = 0.8249) were not significantly different. Conclusion: This preliminary result indicates that placental malaria may cause significant increase in the syncytial knots but not foetal capillaries, intervillous spaces, or syncytial necrosis. This finding signifies early maturation of the placenta and may be crucial in understanding perinatal outcomes.


Assuntos
Malária/patologia , Doenças Placentárias/parasitologia , Placenta/patologia , Complicações Parasitárias na Gravidez/patologia , Feminino , Humanos , Fotomicrografia , Doenças Placentárias/patologia , Gravidez
12.
Int J Mol Med ; 43(5): 1939-1950, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864685

RESUMO

Preeclampsia (PE) is a pathological condition that manifests during pregnancy as the occurrence of an abnormal urine protein level and increased blood pressure due to inadequate cytotrophoblast invasion. To elucidate the mechanism underlying PE, the present study primarily focused on the regulatory effects and mechanism of the G protein γ 7 (GNG7) on placental cytotrophoblasts in a rat PE model. Initially, the PE model was established with 45 specific pathogen­free Sprague­Dawley rats (30 females and 15 males). The expression patterns of GNG7, 4E­binding protein 1 (4E­BP1), phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) and mammalian target of rapamycin (mTOR) were examined in the PE rats. Placental cytotrophoblasts isolated from normal and PE rats were treated with a small interfering RNA against GNG7, mTOR signaling pathway activator (HIV­1 Tat) or inhibitor (rapamycin). Following treatment, cell proliferation, differentiation and apoptosis were evaluated, and mTOR signaling pathway­related factors (4E­BP1, p70S6K and mTOR), cell proliferation­related factors (vascular endothelial growth factor and transforming growth factor­ß1), differentiation­related factors [activator protein­2 (AP­2)α and AP­2γ], and apoptosis­related factors [B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein] were determined. Finally, soluble fms­like tyrosine kinase 1 (sFlt­1) and soluble endoglin (sEng) levels were measured via enzyme­linked immunosorbent assay. Initially, the mTOR signaling pathway was inactivated in the placental tissues and cytotrophoblasts in the PE rats. Silencing GNG7 reduced the levels of sFlt­1 and sEng and activated the mTOR signaling pathway. Silencing of GNG7 or activation of the mTOR signaling pathway enhanced cell proliferation and differentiation, but inhibited the apoptosis of placental cytotrophoblasts in the PE rats. Taken together, the results showed that GNG7 silencing repressed apoptosis and enhanced the proliferation and differentiation of placental cytotrophoblasts in PE rats through activation of the mTOR signaling pathway.


Assuntos
Diferenciação Celular , Subunidades gama da Proteína de Ligação ao GTP/genética , Inativação Gênica , Placenta/patologia , Pré-Eclâmpsia/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Trofoblastos/patologia , Animais , Apoptose , Pressão Sanguínea , Proteínas de Transporte/metabolismo , Proliferação de Células , Diástole , Modelos Animais de Doenças , Endoglina/metabolismo , Feminino , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Fosfoproteínas/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/urina , Gravidez , Ratos Sprague-Dawley , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sístole , Regulação para Cima , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
Fertil Steril ; 111(4): 714-721, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30826115

RESUMO

OBJECTIVES: To evaluate the association of fresh and frozen embryo transfer with the development of ischemic placental disease (IPD), hypothesizing that differences in implantation environment affect placentation and thus pregnancy outcomes. DESIGN: We performed a secondary analysis of a retrospective cohort study of deliveries linked to IVF cycles. SETTING: Tertiary hospital and infertility treatment center. PATIENT(S): We included all women who underwent an autologous IVF cycle and had a live-born infant or an intrauterine fetal demise (IUFD). We excluded women less than 18 years of age. INTERVENTION(S): We compared pregnancies resulting from frozen embryo transfer (frozen) cycles with those resulting from fresh embryo transfer (fresh) cycles. MAIN OUTCOME MEASURE(S): The primary outcome was a composite outcome of IPD or IUFD due to placental insufficiency. Ischemic placental disease included pre-eclampsia, placental abruption, and small for gestational age (SGA). We calculated risk ratios (RRs) and 95% confidence intervals (CIs). RESULT(S): Compared with fresh cycles, frozen cycles had a lower risk of IPD or IUFD from placental insufficiency (RR 0.75, 95% CI 0.59-0.97). Frozen cycles also conferred a lower risk of SGA than fresh cycles (RR 0.58, 95% CI 0.41-0.81). Risks of pre-eclampsia (RR 1.3, 95% CI 0.84-1.9) and abruption (RR 1.2, 95% CI 0.56-2.4) were similar. CONCLUSION(S): There was a lower risk of IPD among frozen cycles compared with fresh cycles. This association was largely driven by lower risk of SGA among frozen cycles.


Assuntos
Transferência Embrionária/métodos , Isquemia/etiologia , Doenças Placentárias/epidemiologia , Placenta/irrigação sanguínea , Adulto , Blastocisto , Criopreservação , Transferência Embrionária/efeitos adversos , Feminino , Morte Fetal/etiologia , Congelamento , Humanos , Recém-Nascido , Infertilidade/epidemiologia , Infertilidade/terapia , Isquemia/epidemiologia , Nascimento Vivo/epidemiologia , Masculino , Placenta/patologia , Doenças Placentárias/etiologia , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Fatores de Risco
14.
Arch Endocrinol Metab ; 63(1): 22-29, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30864628

RESUMO

OBJECTIVE: The aim of this study was to evaluate the relationship between inflammatory cytokines, placental weight, glycated hemoglobin and adverse perinatal outcomes (APOs) in women with gestational diabetes mellitus (GDM). SUBJECTS AND METHODS: This was a prospective, longitudinal and observational study conducted from April 2004 to November 2005 in Bauru, Brazil. Included patients had singleton pregnancies and performed a 100 g OGTT and had the levels of C-reactive protein (CRP), interleukin (IL)-6, TNF alfa and glycated hemoglobin (HbA1c) determined at 24-28th gestation weeks. RESULTS: A total of 176 patients were included, of whom 78 had the diagnosis of GDM (44.3%). Multivariate analysis demonstrated that HbA1c, age, body mass index (BMI) and previous history of GDM were independent predictors for GDM diagnosis. ROC curve indicated that HbA1C levels ≥ 5.1% at 24-28 weeks gestation were associated with GDM. No difference was found in IL-6, tumor necrosis factor alpha (TNF-alpha) and CRP serum levels in women with and without GDM. Multivariate analysis showed that placental weight was significantly associated with APOs (p < 0.005), with a cut-off value of 610 grams as demonstrated by the ROC curve. CONCLUSION: Placental weight ≥ 610 grams and HbA1C ≥ 5.1% were found to be associated with APOs and GDM, respectively, and their evaluation should be part of prenatal care routine.


Assuntos
Proteína C-Reativa/análise , Diabetes Gestacional/sangue , Hemoglobina A Glicada/análise , Interleucina-6/sangue , Placenta/patologia , Fator de Necrose Tumoral alfa/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Estudos Longitudinais , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Estudos Prospectivos
15.
Vet Pathol ; 56(4): 555-564, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30895909

RESUMO

The aim of this study was to assess whether pregnant mice represent a useful model to study the reproductive pathology of Campylobacter jejuni IA3902 using the end point of positive microbial culture of the organism from the fetoplacental unit. Pregnant BALB/c and CD-1 mice (14 days' gestation) were inoculated orally and intraperitoneally (IP) with 1 × 109 colony-forming units/ml of C. jejuni IA3902. The organism was recovered by microbial culture from the fetoplacental unit in 10 of 10 BALB/c and 10 of 10 CD-1 IP-inoculated pregnant mice and in 29% (2/7) BALB/c and 38% (3/8) CD-1 orally inoculated pregnant mice. Gross reproductive lesions included necrosuppurative placentitis, fetal resorption, intrauterine fetal death, stillborn pups (dead neonates), and multifocal hepatitis. Histological changes consisted of locally extensive neutrophilic and necrotizing placentitis with intralesional bacterial colonies of C. jejuni, ulcerative endometritis, random multifocal hepatitis, and rare cholecystitis. Immunohistochemistry for the major outer membrane protein of C. jejuni revealed moderate to large numbers of the organism at the periphery of the placental discs, within trophoblasts and extracellularly, with invasion into the placental disc largely via the vascular network. The organism is trophic for neutral mucin, iron, and L-fucose within the murine placenta. C. jejuni IA3902 has affinity for the murine reproductive tract, specifically the fetoplacental unit, where it results in a necrotizing placentitis with positive microbial recovery after both IP and oral challenge in BALB/c and CD-1 pregnant mice.


Assuntos
Infecções por Campylobacter/microbiologia , Campylobacter jejuni/fisiologia , Animais , Infecções por Campylobacter/patologia , Modelos Animais de Doenças , Feminino , Morte Fetal , Imuno-Histoquímica/veterinária , Camundongos , Camundongos Endogâmicos BALB C , Placenta/patologia , Gravidez , Trofoblastos/patologia
16.
Mol Med Rep ; 19(5): 3775-3782, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864732

RESUMO

Insufficient invasion of trophoblasts is known to be associated with preeclampsia (PE) development. Recently, microRNAs (miRNAs) have been reported to serve important roles in the pathogenesis of PE. However, little is known regarding the regulation of trophoblastic invasion by miRNAs. The aim of the present study was to explore the role of miRNAs in trophoblastic invasion and the underlying molecular mechanism. Using a miRNA microarray, miRNAs putatively involved in the pathophysiology of PE were examined between normal and preeclamptic placentas. Validation analysis of miR­142­3p level in placenta specimens was performed using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Then, the regulation of miR­142­3p on trophoblast cells migration and invasion was evaluated using wound healing and transwell migration assays. Furthermore, the target gene of miR­142­3p and the downstream signaling pathway were also investigated. Microarray analysis and RT­qPCR revealed that miR­142­3p was significantly upregulated in placenta specimens from patients with PE. Its overexpression inhibited trophoblast cell invasion and migration, whereas its knockdown enhanced trophoblast cell invasion and migration. In addition, overexpression of miR­142­3p inhibited the mRNA expression and the activities of matrix metalloproteinase­2 (MMP2) and MMP9, which are closely associated with cell invasion and migration, while inhibition of miR­142­3p had the opposite result. Subsequent analyses demonstrated that transforming growth factor­ß1 (TGF­ß1) was a direct and functional target of miR­142­3p. Notably, the knockdown of TGF­ß1 effectively reversed the enhancement of miR­142­3p inhibitor on trophoblast cell invasion and migration. Finally, the present study confirmed that miR­142­3p inhibitor enhanced cell invasion and migration by reactivating the TGF­ß1/Smad3 signaling pathway. Taken together, the results of the present study suggest that miR­142­3p may serve an important role in human placental development by suppressing trophoblast cell invasion and migration through disruption of the TGF­ß1/smad3 signaling pathway, suggesting that knockdown of miR­142­3p may provide a novel therapy for PE.


Assuntos
Movimento Celular , MicroRNAs/genética , Placenta/patologia , Pré-Eclâmpsia/patologia , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Trofoblastos/patologia , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Placenta/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Transdução de Sinais , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética , Trofoblastos/metabolismo
17.
Medicine (Baltimore) ; 98(8): e14554, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813167

RESUMO

RATIONALE: We report a rare case of a pregnant woman with placental mesenchymal dysplasia (PMD) and intrauterine growth restriction (IUGR) with a genetically normal fetus. PATIENT CONCERNS: A 42-year-old woman Gravida I, Para I with pre-existent uncontrolled hypertension and uterine polyfibromatosis present at 30 weeks of gestation for diminished fetal activity during the last 2 days. DIAGNOSIS: Placental mesenchymal dysplasia associated with intrauterine growth restriction, hypertension, and uterine polyfibromatosis. INTERVENTION: A live male infant was delivered by emergency caesarean section. OUTCOMES: The infant, weighing 700 g, died 4 days after birth due to a massive intracerebral hemorrhage. LESSONS: A careful examination should be done at every ultrasound in case of a fetus with IUGR to exclude some rare cases of placental pathologies. PMD can be a rare cause of IUGR with a genetically normal fetus.


Assuntos
Cesárea/métodos , Retardo do Crescimento Fetal/etiologia , Doenças Placentárias/diagnóstico , Adulto , Feminino , Feto/patologia , Humanos , Hipertensão/complicações , Leiomioma/complicações , Masculino , Morte Perinatal/etiologia , Placenta/patologia , Gravidez , Ultrassonografia Pré-Natal/métodos
18.
EBioMedicine ; 41: 610-622, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30827932

RESUMO

BACKGROUND: We recently demonstrated the increased abundance of anti-trophoblast antibodies (ATAB) in sera of patients with unexplained recurrent miscarriages (uRM). Further, the ATAB-positive sera bound to JEG-3 human choriocarcinoma cells in vitro, resulting in decreased productions of ß-human chorionic gonadotropin (ß-hCG) and progesterone in these cells. However, the specific antigenic epitopes of ATAB have remained unknown. Therefore, it was the aim of this study to determine specific targets of ATAB in uRM patients. METHODS: Potential targets of ATAB were analyzed by 2-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry, and thereby identifying α-Enolase (ENO1). ATAB targeting of ENO1 was further confirmed in a competitive binding assay. Levels of anti-ENO1 antibodies as well as ß-hCG and progesterone were quantified with enzyme-linked immunosorbent assay (ELISA). Additionally, expression of ENO1 was analyzed in first trimester placentas by immunohistochemistry and immunofluorescence analysis. FINDINGS: We here identified ENO1 as a prominent target of ATAB. Serum levels of anti-ENO1 antibodies were increased in ATAB-positive compared to ATAB-negative patients. Further, increased expression of ENO1 and its co-expression with ß-arrestin was found in the extra villous trophoblasts of uRM patients in first trimester placentas. In vitro, anti-ENO1 antibodies decreased the secretion of ß-hCG and progesterone in JEG-3 and primary human villous trophoblast cells. INTERPRETATION: Serum anti-ENO1 antibodies might be an autoimmune biomarker for uRM. Targeting the formation of anti-ENO1 antibodies or inhibition of ENO1 expression could potentially represent therapeutic strategies for these patients. FUND: All authors declare no conflict of interest. Yao Ye was supported by the China Scholarship Council. Hellen Ishikawa-Ankerhold and Christian Schulz were supported by the SFB914, projects Z01 and A10. None of the rest authors has any conflict of interest to declare.


Assuntos
Aborto Habitual/diagnóstico , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Biomarcadores/sangue , Fosfopiruvato Hidratase/imunologia , Aborto Habitual/patologia , Linhagem Celular Tumoral , Gonadotropina Coriônica/análise , Gonadotropina Coriônica/metabolismo , Citocinas , Eletroforese em Gel Bidimensional , Feminino , Humanos , Espectrometria de Massas , Microscopia Confocal , Placenta/metabolismo , Placenta/patologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Gravidez , Progesterona/análise , Progesterona/metabolismo , Trofoblastos/citologia , Trofoblastos/imunologia , Trofoblastos/patologia
19.
Nature ; 567(7746): 105-108, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30787433

RESUMO

Genomic instability can trigger cellular responses that include checkpoint activation, senescence and inflammation1,2. Although genomic instability has been extensively studied in cell culture and cancer paradigms, little is known about its effect during embryonic development, a period of rapid cellular proliferation. Here we report that mutations in the heterohexameric minichromosome maintenance complex-the DNA replicative helicase comprising MCM2 to MCM73,4-that cause genomic instability render female mouse embryos markedly more susceptible than males to embryonic lethality. This bias was not attributable to X chromosome-inactivation defects, differential replication licensing or X versus Y chromosome size, but rather to 'maleness'-XX embryos could be rescued by transgene-mediated sex reversal or testosterone administration. The ability of exogenous or endogenous testosterone to protect embryos was related to its anti-inflammatory properties5. Ibuprofen, a non-steroidal anti-inflammatory drug, rescued female embryos that contained mutations in not only the Mcm genes but also the Fancm gene; similar to MCM mutants, Fancm mutant embryos have increased levels of genomic instability (measured as the number of cells with micronuclei) from compromised replication fork repair6. In addition, deficiency in the anti-inflammatory IL10 receptor was synthetically lethal with the Mcm4Chaos3 helicase mutant. Our experiments indicate that, during development, DNA damage associated with DNA replication induces inflammation that is preferentially lethal to female embryos, because male embryos are protected by high levels of intrinsic testosterone.


Assuntos
Perda do Embrião/genética , Instabilidade Genômica/genética , Inflamação/genética , Proteínas de Manutenção de Minicromossomo/genética , Mutação , Caracteres Sexuais , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Proliferação de Células , Dano ao DNA , DNA Helicases/genética , Replicação do DNA , Perda do Embrião/patologia , Perda do Embrião/prevenção & controle , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/genética , Feminino , Ibuprofeno/farmacologia , Inflamação/patologia , Inflamação/prevenção & controle , Masculino , Camundongos , Componente 4 do Complexo de Manutenção de Minicromossomo/genética , Proteínas de Manutenção de Minicromossomo/deficiência , Placenta/metabolismo , Placenta/patologia , Gravidez , Receptores de Interleucina-10/deficiência , Receptores de Interleucina-10/genética , Mutações Sintéticas Letais , Testosterona/farmacologia
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