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1.
BMJ Case Rep ; 14(5)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059548

RESUMO

A 31-year-old woman with a history of stillbirth due to placental abruption at 29 weeks' gestation and one first trimester miscarriage documented a continuous record of her perceived fetal movements from 28 to 38 weeks' gestation. Repeated ultrasound examinations confirmed a viable pregnancy, with normal growth, liquor volume and Doppler profile. She delivered a healthy male infant at 38 weeks and 3 days' gestation. The data collected give a detailed record of fetal activity in a healthy pregnancy. Perceived fetal activity increased as pregnancy progressed and was greatest in the evenings. We also found that clusters of movements, which have previously been reported as protective against stillbirth, were felt earlier on in pregnancy.


Assuntos
Movimento Fetal , Placenta , Adulto , Feminino , Humanos , Masculino , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Natimorto
2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(6): 538-545, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34060449

RESUMO

Objective To investigate the changes of key factors such as placental villi and lymph vessels in chronic venous disease (CVD) during pregnancy. Methods According to the CEAP classification criteria, tissues of CVD patients were collected, and was divided into control group and CVD group. Real-time quantitative PCR was used to detect mRNA level of CD31, D2-4, fms-related tyrosine kinase 1 (FLT-1), placental growth factor (PlGF) and hypoxia-inducible factor-1 (HIF-1α) in placental tissues. Immohistochemical staining was performed to measure the expression level of CD31, D2-40, FLT-1, PlGF, HIF-1α, B-cell lymphoma 2 (Bcl2), Bcl2-related X protein (BAX), caspase 3 and caspase-9. The change in average number of syncytiotrophoblast cell nodes in placental villi was observed by optical microscope and transmission electron microscope. Periodic acid Schiff (PAS) staining was used to detect the PAS-positive substances in placental villi. Results Compared with the control group, the average numbers of placenta villi, syncytiotrophoblast cell nodes, syncytiotrophoblast cell nodes/villi and the connection bridges between villi of the average syncytrotrophoblast cells increased significantly in the CVD group, while the average number of fibrinoid necrosis showed no significant changes. The mRNA levels of CD31, D2-40, FLT-1, PlGF, and HIF-1α in the CVD group also increased significantly, and the proportion of villi cells positive of BAX, caspase-3 and caspase-9 rose significantly, while that of villi cells positive positive of Bcl2 showed no obvious change. CVD group also reported a marked increase in the number of blood vessels positive of CD31, D2-40, FLT-1 and PlGF. The expression level of HIF-1α in syncytiotrophoblast cells, cytotrophoblast cells and fetal capillary villi increased significantly in the CVD group. The percentage of placenta with PAS positive substances observed an increase in the villi, in comparison to the control group. Conclusion The production of blood vessels and lymph vessels increased in the placental villi of patients with CVD, coupled with an accelerated apoptosis of villi cells. Meanwhile, CVD patients show an impaired function of placental villi and obstructed gas exchange between mother and infant.


Assuntos
Linfangiogênese , Placenta , Apoptose , Vilosidades Coriônicas , Feminino , Humanos , Fator de Crescimento Placentário , Gravidez
3.
Chemosphere ; 276: 130213, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34088095

RESUMO

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by a variety of alternatives in consumer products. Due to their structural similarity to BPA, these alternatives are under surveillance, however, for potential endocrine disruption. Understanding the materno-fetal transfer of these BPA-related alternatives across the placenta is therefore crucial to assess prenatal exposure risks. The objective of the study was to assess and compare the placental transfer of a set of 15 selected bisphenols (BPs) (BP 4-4, BPA, BPAF, BPAP, 3-3 BPA, BPB, BPBP, BPC, BPE, BPF, BPFL, BPM, BPP, BPS and BPZ) using the ex vivo human placental perfusion model. The UHPLC-MS/MS method for simultaneous quantification of these BPs in perfusion media, within a concentration range of 0.003-5 µM, was able to measure placenta transfer rates as low as 0.6%-4%. Despite their structural similarities, these BPs differed greatly in placental transport efficiency. The placental transfer rates of BP4-4, BPAP, BPE, BPF, 3-3BPA, BPB, BPA were similar to that of antipyrine, indicating that their main transport mechanism was passive diffusion. By contrast, the placental transfer rates of BPFL and BPS were very limited, and intermediate for BPBP, BPZ, BPC, BPM, BPP and BPAF, suggesting weak diffusional permeability and/or that their passage might involve efflux transport. These placental transfer data will be particularly useful for predicting the fetal exposure of this important class of emerging contaminants.


Assuntos
Placenta , Espectrometria de Massas em Tandem , Compostos Benzidrílicos , Feminino , Humanos , Perfusão , Fenóis , Gravidez
4.
Viruses ; 13(6)2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073492

RESUMO

The current coronavirus pandemic has affected, in a short time, various and different areas of medicine. Among these, the obstetric field has certainly been touched in full, and the knowledge of the mechanisms potentially responsible for placental damage from SARS-CoV-2 occupy a certain importance. Here we present here a rare case of dichorionic twins born at 30 weeks and 4 days of amenorrhea, one of whom died in the first few hours of life after placental damages potentially related to SARS-CoV-2. We also propose a brief review of the current literature giving ample emphasis to similar cases described.


Assuntos
COVID-19/complicações , Placenta/patologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/patogenicidade , Adulto , COVID-19/diagnóstico , COVID-19/transmissão , COVID-19/virologia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Complicações do Trabalho de Parto/virologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Resultado da Gravidez , Gravidez de Gêmeos , SARS-CoV-2/isolamento & purificação
5.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064719

RESUMO

Inflammation is a major cause of several chronic diseases and is reported to be recovered by the immuno-modulation of mesenchymal stem cells (MSCs). While most studies have focussed on the anti-inflammatory roles of MSCs in stem cell therapy, the impaired features of MSCs, such as the loss of homeostasis by systemic aging or pathologic conditions, remain incompletely understood. In this study, we investigated whether the altered phenotypes of human placenta-derived MSCs (hPD-MSCs) exposed to inflammatory cytokines, including TNF-α and IFN-γ, could be protected by MIT-001, a small anti-inflammatory and anti-necrotic molecule. MIT-001 promoted the spindle-like shape and cytoskeletal organization extending across the long cell axis, whereas hPD-MSCs exposed to TNF-α/IFN-γ exhibited increased morphological heterogeneity with an abnormal cell shape and cytoskeletal disorganization. Importantly, MIT-001 improved mitochondrial distribution across the cytoplasm. MIT-001 significantly reduced basal respiration, ATP production, and cellular ROS levels and augmented the spare respiratory capacity compared to TNF-α/IFN-γ-exposed hPD-MSCs, indicating enhanced mitochondrial quiescence and homeostasis. In conclusion, while TNF-α/IFN-γ-exposed MSCs lost homeostasis and mitochondrial quiescence by becoming over-activated in response to inflammatory cytokines, MIT-001 was able to rescue mitochondrial features and cellular phenotypes. Therefore, MIT-001 has therapeutic potential for clinical applications to treat mitochondrion-related inflammatory diseases.


Assuntos
Citoesqueleto/fisiologia , Células-Tronco Mesenquimais/fisiologia , Mitocôndrias/fisiologia , Compostos Orgânicos/farmacologia , Placenta/citologia , Citoesqueleto/efeitos dos fármacos , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Consumo de Oxigênio , Placenta/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Espécies Reativas de Oxigênio/metabolismo
6.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071527

RESUMO

A pandemic of acute respiratory infections, due to a new type of coronavirus, can cause Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) and has created the need for a better understanding of the clinical, epidemiological, and pathological features of COVID-19, especially in high-risk groups, such as pregnant women. Viral infections in pregnant women may have a much more severe course, and result in an increase in the rate of complications, including spontaneous abortion, stillbirth, and premature birth-which may cause long-term consequences in the offspring. In this review, we focus on the mother-fetal-placenta interface and its role in the potential transmission of SARS-CoV-2, including expression of viral receptors and proteases, placental pathology, and the presence of the virus in neonatal tissues and fluids. This review summarizes the current knowledge on the anti-viral activity of lactoferrin during viral infection in pregnant women, analyzes its role in the pathogenicity of pandemic virus particles, and describes the potential evidence for placental blocking/limiting of the transmission of the virus.


Assuntos
Anti-Infecciosos/farmacologia , COVID-19/imunologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Lactoferrina/farmacologia , Placenta/imunologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/imunologia , COVID-19/complicações , Feminino , Humanos , Recém-Nascido , Lactoferrina/metabolismo , Placenta/patologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-34073422

RESUMO

There are reports that pregnant women infected with SARS-CoV-2 not only have increased morbidity but also increased complications and evidence of maternal and fetal vascular malperfusion on placental pathology. This was a retrospective study of pregnant women diagnosed with SARS-CoV-2 infection after March 2020. The results of reverse transcription polymerase chain reaction testing and IgM and IgG antibody testing of the amniotic fluid, cord blood, placenta, and maternal blood were confirmed at delivery. Placentas were evaluated histopathologically. The study included seven pregnant women diagnosed with SARS-CoV-2 infection during pregnancy at a mean gestational age of 14.5 weeks. Out of the seven women, five were infected during the first trimester. The mean gestational age at delivery was 38.4 weeks. The reverse transcription polymerase chain reaction results for maternal plasma, cord blood, placenta, and amniotic fluid were negative and IgG antibodies were detected in maternal plasma and cord blood. On placental pathology, maternal vascular malperfusion was found in only one case, fetal vascular malperfusion in four cases, and inflammatory changes were found in two cases. Pregnancy outcomes for women diagnosed with SARS-CoV-2 infection during early pregnancy are positive and it is likely that maternal antibodies are passed to the fetus, which results in a period of immunity.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Placenta , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , SARS-CoV-2
8.
Am J Case Rep ; 22: e931156, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34127641

RESUMO

BACKGROUND Gestational trophoblastic disease (GTD) is a spectrum of disorders consisting of premalignant (ie, complete [CHM] and partial hydatidiform moles [PHM]) and malignant conditions (ie, invasive moles, choriocarcinoma, placental site trophoblastic tumors, and epithelioid trophoblastic tumor). If GTD persists after initial treatment and has persistent elevated beta human chorionic gonadotropin (ß-hCG), it is referred to as post-molar gestational trophoblastic neoplasia (pGTN). To date, there is no detailed information regarding how fast invasive moles can develop from CHM. However, the risk of developing any pGTN from CHM is rare within 1 month and is greatest in the first 12 months after evacuation, with most cases presenting within 6 months. CASE REPORT We present a case of a 46-year-old primigravida woman with rapid transformation of an invasive mole. In the beginning, the patient had a chief concern of a uterus size greater than the gestational dates. Laboratory evaluation showed high ß-hCG serum level (>300 000 mIU/mL), and ultrasonography evaluation revealed a hydatidiform mole. Suction evacuation and curettage procedures were then performed. Pathology evaluation afterwards revealed a complete hydatidiform mole without any sign of malignancy. Twenty-two days afterwards, the patient came to the emergency room with vaginal bleeding. ß-hCG serum level was high (53 969 mIU/mL), and ultrasonography examination showed the presence of fluid filling the uterine cavity. The patient was then diagnosed with GTN, and hysterectomy was chosen as the treatment of choice. After the surgery, her ß-hCG serum level gradually reverted back to normal. CONCLUSIONS Invasive moles can develop less than 1 month after suction evacuation and curettage procedure for CHM. Serial ß-hCG serum level evaluation according to the guideline should be performed to prevent late diagnosis, which could lead to the development of metastasis and worsen the prognosis.


Assuntos
Mola Hidatiforme Invasiva , Mola Hidatiforme , Neoplasias Uterinas , Gonadotropina Coriônica , Feminino , Seguimentos , Humanos , Mola Hidatiforme/diagnóstico , Pessoa de Meia-Idade , Placenta , Gravidez , Neoplasias Uterinas/diagnóstico
9.
Braz J Med Biol Res ; 54(9): e9570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34133541

RESUMO

High proportions of placental lymphocytes expressing DX5+/CD25+/FOXP3+/CD45+/CD4+ are beneficial to maintain immune tolerance and improve pregnancy outcomes. This study aimed to compare and evaluate the therapeutic effects of aspirin, vitamin D3 (VitD3), and progesterone on the autoimmune recurrent spontaneous abortion (RSA) model. The autoimmune RSA mouse model was constructed, and the embryo loss rate was calculated for each group. Then, primary mouse placental lymphocytes were isolated, and the expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ was detected through flow cytometry. The serum levels of anti-cardiolipin antibody (ACA), ß2-GP1, CXCL6, IFN-γ, and IL-6 were measured by ELISA to evaluate the proportion of Th1 and Th2 cells. Autoimmune RSA significantly increased the embryo loss rate, which was improved by aspirin, VitD3, and progesterone treatment, and progesterone treatment had the best effect among the three treatments. The positive expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ in the VitD3 and progesterone groups was significantly higher than that in the autoimmune RSA group, and the expression was highest in the progesterone treatment group. In the plasma of autoimmune RSA mice, the ACA, ß2-GP1, CXCL6, and IFN-γ levels were significantly higher and the IL-6 level was lower than the levels in control mice. All these changes could be reversed by aspirin and progesterone treatment. In conclusion, aspirin, VitD3 and progesterone treatment improved pregnancy outcomes in autoimmune RSA mice by regulating the Th1/Th2 balance and cytokines, and progesterone had the best effect of the three treatments.


Assuntos
Aborto Habitual , Progesterona , Aborto Habitual/tratamento farmacológico , Aborto Habitual/prevenção & controle , Animais , Aspirina , Colecalciferol/uso terapêutico , Feminino , Humanos , Camundongos , Placenta , Gravidez , Resultado da Gravidez
10.
Nat Commun ; 12(1): 2639, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976128

RESUMO

The placenta is the interface between mother and fetus and inadequate function contributes to short and long-term ill-health. The placenta is absent from most large-scale RNA-Seq datasets. We therefore analyze long and small RNAs (~101 and 20 million reads per sample respectively) from 302 human placentas, including 94 cases of preeclampsia (PE) and 56 cases of fetal growth restriction (FGR). The placental transcriptome has the seventh lowest complexity of 50 human tissues: 271 genes account for 50% of all reads. We identify multiple circular RNAs and validate 6 of these by Sanger sequencing across the back-splice junction. Using large-scale mass spectrometry datasets, we find strong evidence of peptides produced by translation of two circular RNAs. We also identify novel piRNAs which are clustered on Chr1 and Chr14. PE and FGR are associated with multiple and overlapping differences in mRNA, lincRNA and circRNA but fewer consistent differences in small RNAs. Of the three protein coding genes differentially expressed in both PE and FGR, one encodes a secreted protein FSTL3 (follistatin-like 3). Elevated serum levels of FSTL3 in pregnant women are predictive of subsequent PE and FGR. To aid visualization of our placenta transcriptome data, we develop a web application ( https://www.obgyn.cam.ac.uk/placentome/ ).


Assuntos
Retardo do Crescimento Fetal/genética , Placenta/patologia , Pré-Eclâmpsia/genética , RNA/genética , Transcriptoma/genética , Biópsia , Conjuntos de Dados como Assunto , Feminino , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/patologia , Proteínas Relacionadas à Folistatina/sangue , Proteínas Relacionadas à Folistatina/genética , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/patologia , Gravidez , RNA/metabolismo , RNA-Seq
11.
BMC Ecol Evol ; 21(1): 76, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941077

RESUMO

BACKGROUND: There has been a rapid increase in the brain size relative to body size during mammalian evolutionary history. In particular, the enlarged and globular brain is the most distinctive anatomical feature of modern humans that set us apart from other extinct and extant primate species. Genetic basis of large brain size in modern humans has largely remained enigmatic. Genes associated with the pathological reduction of brain size (primary microcephaly-MCPH) have the characteristics and functions to be considered ideal candidates to unravel the genetic basis of evolutionary enlargement of human brain size. For instance, the brain size of microcephaly patients is similar to the brain size of Pan troglodyte and the very early hominids like the Sahelanthropus tchadensis and Australopithecus afarensis. RESULTS: The present study investigates the molecular evolutionary history of subset of autosomal recessive primary microcephaly (MCPH) genes; CEP135, ZNF335, PHC1, SASS6, CDK6, MFSD2A, CIT, and KIF14 across 48 mammalian species. Codon based substitutions site analysis indicated that ZNF335, SASS6, CIT, and KIF14 have experienced positive selection in eutherian evolutionary history. Estimation of divergent selection pressure revealed that almost all of the MCPH genes analyzed in the present study have maintained their functions throughout the history of placental mammals. Contrary to our expectations, human-specific adoptive evolution was not detected for any of the MCPH genes analyzed in the present study. CONCLUSION: Based on these data it can be inferred that protein-coding sequence of MCPH genes might not be the sole determinant of increase in relative brain size during primate evolutionary history.


Assuntos
Microcefalia , Animais , Encéfalo , Evolução Molecular , Feminino , Humanos , Microcefalia/genética , Placenta , Gravidez , Primatas/genética
12.
Clin Nutr ESPEN ; 43: 1-8, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34024500

RESUMO

BACKGROUND & AIMS: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders. Maternal immune activation in animals models this pathophysiology. SARS-CoV-2 produces maternal inflammatory responses during pregnancy similar to previously studied common respiratory viruses. METHOD: Choline, folic acid, Vitamin D, and n-3 polyunsaturated fatty acids are among the nutrients that have been studied as possible mitigating factors for effects of maternal infection and inflammation on fetal development. Clinical and animal studies relevant to their use in pregnant women who have been infected are reviewed. RESULTS: Higher maternal choline levels have positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy. No other nutrient has been studied in the context of viral inflammation. Vitamin D reduces pro-inflammatory cytokines in some, but not all, studies. Active folic acid metabolites decrease anti-inflammatory cytokines. N-3 polyunsaturated fatty acids have no effect. CONCLUSIONS: Vitamin D and folic acid are already supplemented in food additives and in prenatal vitamins. Despite recommendations by several public health agencies and medical societies, choline intake is often inadequate in early gestation when the brain is forming. A public health initiative for choline supplements during the pandemic could be helpful for women planning or already pregnant who also become exposed or infected with SARS-CoV-2.


Assuntos
Encéfalo , COVID-19/complicações , Colina/uso terapêutico , Desenvolvimento Fetal , Mães , Estado Nutricional , Complicações Infecciosas na Gravidez/virologia , Animais , Encéfalo/efeitos dos fármacos , COVID-19/metabolismo , COVID-19/virologia , Desenvolvimento Infantil/efeitos dos fármacos , Colina/farmacologia , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Feto/efeitos dos fármacos , Ácido Fólico/farmacologia , Ácido Fólico/uso terapêutico , Humanos , Lactente , Inflamação/complicações , Inflamação/metabolismo , Necessidades Nutricionais , Pandemias , Placenta/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , SARS-CoV-2 , Vitamina D/farmacologia , Vitamina D/uso terapêutico
13.
Braz J Med Biol Res ; 54(8): e11073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037098

RESUMO

The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eight PE women, and supernatants were obtained after incubation with or without hydrogen peroxide (H2O2) and/or VD. HUVEC were cultured for 24 h with supernatants, and the following parameters were analyzed in HUVEC cultures: NO, nitrate (NO3-), and nitrite (NO2-) levels, lipid peroxidation, and intracellular reactive oxygen species (ROS). Results showed that the production of NO3-, NO2-, malondialdehyde (MDA), and ROS were significantly higher in HUVEC treated with explant supernatant from PE compared to NT pregnant women, while the supernatant of PE explants treated with VD led to a decrease in these parameters. A significantly high production of NO was detected in HUVEC cultured with control supernatant of NT group, and in cultures treated with supernatant of PE explants treated with VD. Taken together, these results demonstrated that cultures of placental explants from PE women with VD treatment generated a supernatant that decreased oxidative stress and increased the bioavailability of NO in endothelial cells.


Assuntos
Óxido Nítrico , Pré-Eclâmpsia , Disponibilidade Biológica , Células Cultivadas , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio , Óxido Nítrico/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Vitamina D/metabolismo
14.
Klin Lab Diagn ; 66(5): 266-270, 2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34047511

RESUMO

The content of metal ions and proteins containing or binding these metals in amniotic fluid during different periods of physiological pregnancy and placental insufficiency (PI) was studied. The content of zinc, copper, magnesium, iron, zinc-α-2-glycoprotein, ferritin, ceruloplasmin and the activity of Ca2+, Mg2+-ATPase were estimated using spectrophotometric methods, immunoturbometric and enzyme immunoassay methods. It was found that in PI in both trimesters there is a decrease in the content of zinc, copper, iron and an increase in the level of copper. The indices of ceruloplasmin, ferritin, Ca2+, Mg2+-ATPase in PI are lower, and zinc-α-2-glycoprotein is higher than in similar periods of physiological gestation. A close correlation of different directions has been established between the level of metals and the corresponding proteins. The revealed violations obviously play a certain pathogenetic role in the development of PI, and the indicators of the ratio between metals can serve as markers for predicting the state of newborns.


Assuntos
Líquido Amniótico , Insuficiência Placentária , Cobre , Feminino , Humanos , Recém-Nascido , Metais , Placenta , Gravidez
15.
Nat Commun ; 12(1): 2956, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011972

RESUMO

Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of VAR2CSA in complex with placental CS, we identify the CS-binding groove, intersecting with the positively charged patch of the central VAR2CSA structure. We identify distinctive conserved structural features upholding the macro-molecular domain complex and CS binding capacity of VAR2CSA as well as divergent elements possibly allowing immune escape at or near the CS binding site. These observations will support rational design of second-generation placental malaria vaccines.


Assuntos
Antígenos de Protozoários/química , Antígenos de Protozoários/metabolismo , Sulfatos de Condroitina/metabolismo , Malária Falciparum/complicações , Placenta/parasitologia , Complicações Parasitárias na Gravidez/metabolismo , Complicações Parasitárias na Gravidez/parasitologia , Sequência de Aminoácidos , Antígenos de Protozoários/genética , Microscopia Crioeletrônica , Feminino , Humanos , Evasão da Resposta Imune , Malária Falciparum/metabolismo , Malária Falciparum/parasitologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutagênese , Placenta/imunologia , Placenta/metabolismo , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Plasmodium falciparum/patogenicidade , Gravidez , Ligação Proteica , Domínios Proteicos
17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 33(2): 177-187, 2021 Apr 16.
Artigo em Chinês | MEDLINE | ID: mdl-34008365

RESUMO

OBJECTIVE: To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). METHODS: A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. RESULTS: Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (rs = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (rs = 0.97, P < 0.01) and in placental (rs = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (rs = 0.81, P < 0.01). CONCLUSIONS: Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.


Assuntos
Toxoplasma , Animais , Antígeno B7-H1/genética , Feminino , Interferon gama/genética , Camundongos , Placenta , Gravidez , Receptor de Morte Celular Programada 1
18.
Placenta ; 109: 72-74, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34034016

RESUMO

Whether early SARS-CoV-2 definitively increases the risk of stillbirth is unknown, though studies have suggested possible trends of stillbirth increase during the pandemic. This study of third trimester stillbirth does not identify an increase in rates during the first wave of the pandemic period, however investigation of the placental pathology demonstrates trends towards more vascular placental abnormalities.


Assuntos
COVID-19/epidemiologia , Doenças Placentárias/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Terceiro Trimestre da Gravidez , Natimorto/epidemiologia , Adulto , COVID-19/complicações , COVID-19/mortalidade , Causas de Morte , Feminino , Morte Fetal/etiologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Pandemias , Placenta/patologia , Doenças Placentárias/etiologia , Doenças Placentárias/patologia , Doenças Placentárias/virologia , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , SARS-CoV-2/fisiologia , Estados Unidos/epidemiologia , Adulto Jovem
19.
Sci Total Environ ; 785: 147287, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933771

RESUMO

The placental transfer and congener composition of organic contaminants (OCs) in Indo-Pacific humpback dolphins have been little studied. In the present study, 16 polycyclic aromatic hydrocarbons (PAHs), 18 organochlorine pesticides (OCPs), and 28 polychlorinated biphenyl (PCB) congeners were analyzed in muscle, lung, liver, kidney, and blubber tissues from three mother-fetus pairs of this species stranded along the Pearl River Estuary, China. For PCBs, tetra-, penta-, hexa-, and hepta-chlorobenzene congeners were dominant in all the analyzed samples. Among them, hexachlorobenzene congeners showed the highest level in most dolphin mother-fetus tissue samples. The concentrations of PCBs and OCPs in adult females were higher in the detoxification organs (liver and kidneys) than in the muscles and lungs, whereas muscle tissues in fetuses generally exhibited higher PCBs and OCPs levels than the livers and kidneys. The most abundant PAHs in the four tissues were those with lower molecular weights, which were also the most water-soluble and bioavailable. Negative correlations between the octanol/water partition coefficients (log KOW) and the fetus/mother ratios for PCB congeners revealed that the transfer of PCBs may be determined by their lipid solubility. OCPs and PCBs with low molecular weights and low log KOW values would be more likely to accumulate in the dolphin liver, lung, kidney and muscle tissues. Furthermore, OCs with low molecular weights and low log KOW values were more concentrated in the fetal blubber, lung, and liver tissues than in their respective mothers. The ubiquitous existence of OCs in the mother-fetus pairs strongly suggested that these contaminants could pass through the placenta and partition in fetal tissue. The high transfer efficiency of PAHs and PCBs indicated that the placenta might not be an efficient barrier for these pollutants. PCBs levels in both mother and fetus dolphins could cause immunosuppression.


Assuntos
Golfinhos , Hidrocarbonetos Clorados , Bifenilos Policlorados , Poluentes Químicos da Água , Animais , Bioacumulação , China , Feminino , Hidrocarbonetos Clorados/análise , Placenta/química , Bifenilos Policlorados/análise , Gravidez , Poluentes Químicos da Água/análise
20.
BMJ Case Rep ; 14(5)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039542

RESUMO

Mixed gestational trophoblastic neoplasias (GTNs) are rare placental tumours that arise from abnormal fertilisation events. To date, only 34 patients with mixed GTNs have been reported in the literature. As such, the management of such cases remains challenging. This report presents a case of a mixed GTN that was further complicated by a synchronous primary lung adenocarcinoma. Our patient was initially treated with hysterectomy, with surveillance labwork showing persistence of her malignancy. She then began combination chemotherapy, at the end of which she appeared to be in remission clinically. Unfortunately, subsequent imaging showed the persistence of pulmonary nodules that were ultimately resected, demonstrating a new primary lung adenocarcinoma. At present, she remains free of both cancers 2 years after her initial diagnosis. The complexity of this case underscores the importance of patient-centred treatment for rare tumours and the role of a multidisciplinary team in the effort to provide holistic care.


Assuntos
Doença Trofoblástica Gestacional , Neoplasias Pulmonares , Neoplasias Uterinas , Feminino , Doença Trofoblástica Gestacional/diagnóstico por imagem , Doença Trofoblástica Gestacional/terapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Placenta , Gravidez , Estudos Retrospectivos
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