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1.
Eur J Obstet Gynecol Reprod Biol ; 259: 7-11, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33556768

RESUMO

BACKGROUND: The pandemic of the severe acute respiratory distress syndrome-associated Coronavirus-2 (SARS-CoV-2) has affected millions around the world. In pregnancy the dangers to the mother and fetus are still being explored. SARS-CoV2 can potentially compromise maternal and neonatal outcomes and this may be dependent on the pregnancy stage during which the infection occurs. OBJECTIVE: The present study was done to find the histopathological alterations in the placenta of SARS-CoV-2 positive pregnancies with either no symptoms or mild coronavirus disease (COVID)-19 related symptoms and its association with neonatal outcomes. STUDY DESIGN: This was a prospective analytical study. Twenty seven asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women with a singleton pregnancy delivered between 1st July 2020 and 15th September 2020, were included as cases. An equal number of SARS-CoV-2 negative singleton pregnancies matched for maternal and gestational age during the same period were included as controls. After delivery the histopathological examination of the placenta of these women was done and the findings recorded on a predesigned proforma based on the Amsterdam consensus criteria for evidence of maternal and fetal vascular malperfusion changes. RESULTS: The baseline characteristics were comparable between the cases and controls. The following features of maternal vascular malperfusion (MVM) were significantly higher in the placentae of COVID-19 positive pregnancies: retroplacental hematomas (RPH), accelerated villous maturation (AVM), distal villous hyperplasia (DVH), atherosis, fibrinoid necrosis, mural hypertrophy of membrane arterioles (MHMA), vessel ectasia and persistence of intramural endovascular trophoblast (PIEVT). Fetal vascular malperfusion (FVM) significantly associated with the positive pregnancies were chorioangiosis, thrombosis of the fetal chorionic plate (TFCP), intramural fibrin deposition (IMFD) and vascular ectasia. Additionally, perivillous fibrin deposition was also significantly higher in the placentae of cases. The percentage of spontaneously delivered women was comparable in the two groups. The sex and weight of the newborn and the number of live births were comparable between the two groups. CONCLUSIONS: Asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women, with otherwise uncomplicated pregnancies, show evidence of placental injury at a microscopic level. Similar findings have been demonstrated in other studies too. This placental injury apparently does not lead to poor pregnancy outcomes. The extent of this injury in symptomatic cases of COVID-19 pregnancies and its consequences on the outcomes need to be analysed.


Assuntos
/patologia , Doenças Placentárias/patologia , Placenta/patologia , Complicações Infecciosas na Gravidez/patologia , Adulto , Peso ao Nascer , /fisiopatologia , Portador Sadio , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Masculino , Placenta/irrigação sanguínea , Doenças Placentárias/etiologia , Doenças Placentárias/fisiopatologia , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Resultado da Gravidez , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
2.
Cells ; 10(2)2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578631

RESUMO

Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases; (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.


Assuntos
/complicações , Placenta/irrigação sanguínea , Placenta/patologia , Complicações Cardiovasculares na Gravidez/etiologia , Complicações Infecciosas na Gravidez/etiologia , Trombose/etiologia , Adulto , Antígenos CD/análise , /virologia , Caderinas/análise , Claudina-5/análise , Endotélio/irrigação sanguínea , Endotélio/patologia , Endotélio/virologia , Feminino , Humanos , Recém-Nascido , Microvasos/patologia , Microvasos/virologia , Gravidez , Complicações Cardiovasculares na Gravidez/patologia , Complicações Cardiovasculares na Gravidez/virologia , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Trombose/patologia , Trombose/virologia , Adulto Jovem , Fator de von Willebrand/análise
3.
Am J Physiol Regul Integr Comp Physiol ; 320(5): R653-R662, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33621475

RESUMO

Currently, there is no effective treatment for placental dysfunction in utero. In a ligated mouse model of fetal growth restriction (FGR), nanoparticle-mediated human insulin-like 1 growth factor (hIGF1) gene delivery (NP-Plac1-hIGF1) increased hIGF1 expression and maintained fetal growth. However, whether it can restore fetal growth remains to be determined. Using the endothelial nitric oxide synthase knockout (eNOS-/-) mouse model, a genetic model of FGR, we found that despite inducing expression of hIGF1 in the placentas treated with NP-Plac1-hIGF1 (P = 0.0425), FGR did not resolve. This was associated with no change to the number of fetal capillaries in the placental labyrinth; an outcome which was increased with NP-Plac1-hIGF1 treatment in the ligated mouse model, despite increased expression of angiopoietin 1 (P = 0.05), and suggested IGF1 signaling in the placenta requires eNOS to modulate placenta angiogenesis. To further assess this hypothesis, BeWo choriocarcinoma cell line and human placental explant cultures were treated with NP-Plac1-hIGF1, oxidative stress was induced with hydrogen peroxide (H2O2), and NOS activity was inhibited using the inhibitor NG-monomethyl-l-arginine (l-NMMA). In both BeWo cells and explants, the protective effect of NP-Plac1-hIGF1 treatment against H2O2-induced cell death/lactate dehydrogenase release was prevented by eNOS inhibition (P = 0.003 and P < 0.0001, respectively). This was associated with an increase in mRNA expression of oxidative stress markers hypoxia inducing factor 1α (HIF1α; P < 0.0001) and ADAM10 (P = 0.0002) in the NP-Plac1-hIGF1 + H2O2 + l-NMMA-treated BeWo cells. These findings show for the first time the requirement of eNOS/NOS in IGF1 signaling in placenta cells that may have implications for placental angiogenesis and fetal growth.


Assuntos
Retardo do Crescimento Fetal/terapia , Feto/irrigação sanguínea , Terapia Genética , Fator de Crescimento Insulin-Like I/metabolismo , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo III/metabolismo , Placenta/irrigação sanguínea , Trofoblastos/enzimologia , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Desenvolvimento Fetal , Retardo do Crescimento Fetal/enzimologia , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/fisiopatologia , Técnicas de Transferência de Genes , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator de Crescimento Insulin-Like I/genética , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanopartículas , Óxido Nítrico Sintase Tipo III/genética , Estresse Oxidativo , Gravidez , Transdução de Sinais , Técnicas de Cultura de Tecidos , Trofoblastos/patologia
4.
BMJ Case Rep ; 14(2)2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558383

RESUMO

Subinvolution of placental sites (SPSs) is a rare but severe cause of secondary postpartum haemorrhage (PPH). SPS is characterised by the abnormal persistence of large, dilated, superficially modified spiral arteries in the absence of retained products of conception. It is an important cause of morbidity and mortality of young women. In this study, we present a case of secondary PPH in a young woman after uncomplicated caesarean delivery who was deemed clinically unstable, and finally, underwent emergent total abdominal hysterectomy. We reviewed the literature with an emphasis on the pathophysiology of this situation. Treatment of patients with SPS includes conservative medical therapy, hysterectomy and fertility-sparing percutaneous embolotherapy.


Assuntos
Histerectomia , Placenta/irrigação sanguínea , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/cirurgia , Adulto , Cesárea/efeitos adversos , Feminino , Humanos , Placenta/patologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/cirurgia , Hemorragia Pós-Parto/patologia , Gravidez
5.
Am J Physiol Regul Integr Comp Physiol ; 320(4): R508-R518, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33501896

RESUMO

The endothelial glycocalyx is a specialized extracellular matrix that covers the apical side of vascular endothelial cells, projecting into the lumen of blood vessels. The composition of the glycocalyx has been studied in great detail, and it is known to be composed of a mixture of proteoglycans, glycosaminoglycans, and glycoproteins. Although this structure was once believed to be a passive physical barrier, it is now recognized as a multifunctional and dynamic structure that participates in many vascular processes, including but not limited to vascular permeability, inflammation, thrombosis, mechanotransduction, and cytokine signaling. Because of its participation in many physiological and pathophysiological states, comprehensive knowledge of the glycocalyx will aid future vascular biologists in their research. With that in mind, this review discusses the biochemical structure of the glycocalyx and its function in many vascular physiological processes. We also briefly review a more recent discovery in glycocalyx biology, the placental glycocalyx.


Assuntos
Vasos Sanguíneos/metabolismo , Células Endoteliais/metabolismo , Glicocálix/metabolismo , Placenta/irrigação sanguínea , Animais , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Células Endoteliais/patologia , Feminino , Glicocálix/patologia , Humanos , Permeabilidade , Circulação Placentária , Gravidez , Transdução de Sinais
6.
Placenta ; 101: 13-29, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32911234

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, was first identified after a cluster of cases in Wuhan, China in December 2019. Whether vertical transmission or placental pathology might occur following maternal infection during pregnancy remains unknown. This review aimed to summarise all studies that examined the placenta or neonates following infection with SARS-CoV-2, or closely related highly pathogenic coronavirus (SARS-CoV-1, or the Middle East respiratory syndrome coronavirus (MERS-CoV)). Structured literature searches found 50 studies that met the inclusion criteria. Twenty studies reported placental histopathology findings in third trimester placentas following maternal SARS-CoV-2 infection. Using the Amsterdam Consensus criteria to categorise the histopathology results, evidence of both fetal vascular malperfusion (35.3% of cases; 95% Confidence Interval (CI) 27.7-43.0%) and maternal vascular malperfusion (46% of cases; 95% CI 38.0-54.0%) were reported, along with evidence of inflammation in the placentas (villitis 8.7% cases, intervillositis 5.3% of cases, chorioamnionitis 6% of cases). The placental pathologies observed in SARS-CoV-2 were consistent with findings following maternal SARS-CoV-1 infection. Of those tested, a minority of neonates (2%) and placental samples tested positive for SARS-CoV-2 infection (21%). Limited conclusions can be drawn about the effect of maternal SARS-CoV-2 infection on placental pathology as most lack control groups and the majority of reports followed third trimester infection. Collaboration to maximise the number of samples examined will increase the reliability and generalisability of findings. A better understanding of the association between maternal SARS-CoV-2 infection and placental pathology will inform maternity care during the coronavirus pandemic.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Transmissão Vertical de Doença Infecciosa , Placenta/patologia , Pneumonia Viral/patologia , Complicações Infecciosas na Gravidez/patologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Feminino , Humanos , Recém-Nascido , Pandemias , Placenta/irrigação sanguínea , Placenta/virologia , Circulação Placentária/fisiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/virologia , Vírus da SARS/patogenicidade , Vírus da SARS/fisiologia
7.
Proc Natl Acad Sci U S A ; 117(40): 24964-24973, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32958663

RESUMO

Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infection of nonpregnant mice, the local lung inflammatory response was contained to the lungs and was self-resolving, whereas in pregnant mice, virus dissemination to major maternal blood vessels, including the aorta, resulted in a peripheral "vascular storm," with elevated proinflammatory and antiviral mediators and the influx of Ly6Clow and Ly6Chigh monocytes, plus neutrophils and T cells. This vascular storm was associated with elevated levels of the adhesion molecules ICAM and VCAM and the pattern-recognition receptors TLR7 and TLR9 in the vascular wall, resulting in profound vascular dysfunction. The sequalae of this IAV-driven vascular storm included placental growth retardation and intrauterine growth restriction, evidence of placental and fetal brain hypoxia, and increased circulating cell free fetal DNA and soluble Flt1. In contrast, IAV infection in nonpregnant mice caused no obvious alterations in endothelial function or vascular inflammation. Therefore, IAV infection during pregnancy drives a significant systemic vascular alteration in pregnant dams, which likely suppresses critical blood flow to the placenta and fetus. This study in mice provides a fundamental mechanistic insight and a paradigm into how an immune response to a respiratory virus, such as IAV, is likely to specifically drive maternal and fetal pathologies during pregnancy.


Assuntos
Imunidade Adaptativa/genética , Imunidade Inata/genética , Inflamação/genética , Vírus da Influenza A/genética , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Feminino , Feto/imunologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/virologia , Vírus da Influenza A/patogenicidade , Influenza Humana/genética , Influenza Humana/imunologia , Influenza Humana/virologia , Glicoproteínas de Membrana/genética , Camundongos , Monócitos/metabolismo , Monócitos/patologia , Placenta/irrigação sanguínea , Placenta/imunologia , Placenta/virologia , Gravidez , Linfócitos T/imunologia , Linfócitos T/virologia , Receptor 7 Toll-Like/genética , Receptor Toll-Like 9/genética
8.
Am J Physiol Heart Circ Physiol ; 319(3): H661-H681, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32762557

RESUMO

Preeclampsia is a major complication of pregnancy manifested as hypertension and often intrauterine growth restriction, but the underlying pathophysiological mechanisms are unclear. Predisposing genetic and environmental factors cause placental maladaptations leading to defective placentation, apoptosis of invasive cytotrophoblasts, inadequate expansive remodeling of the spiral arteries, reduced uteroplacental perfusion pressure, and placental ischemia. Placental ischemia promotes the release of bioactive factors into the maternal circulation, causing an imbalance between antiangiogenic soluble fms-like tyrosine kinase-1 and soluble endoglin and proangiogenic vascular endothelial growth factor, placental growth factor, and transforming growth factor-ß. Placental ischemia also stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin type 1 receptor agonistic autoantibodies. These circulating factors target the vascular endothelium, causing generalized endotheliosis in systemic, renal, cerebral, and hepatic vessels, leading to decreases in endothelium-derived vasodilators such as nitric oxide, prostacyclin, and hyperpolarization factor and increases in vasoconstrictors such as endothelin-1 and thromboxane A2. The bioactive factors also target vascular smooth muscle and enhance the mechanisms of vascular contraction, including cytosolic Ca2+, protein kinase C, and Rho-kinase. The bioactive factors could also target matrix metalloproteinases and the extracellular matrix, causing inadequate vascular remodeling, increased arterial stiffening, and further increases in vascular resistance and hypertension. As therapeutic options are limited, understanding the underlying vascular mechanisms and molecular targets should help design new tools for the detection and management of hypertension in pregnancy and preeclampsia.


Assuntos
Pressão Arterial , Hipertensão Induzida pela Gravidez/metabolismo , Placenta/irrigação sanguínea , Pré-Eclâmpsia/metabolismo , Artéria Uterina/metabolismo , Animais , Feminino , Humanos , Hipertensão Induzida pela Gravidez/etiologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Isquemia/metabolismo , Isquemia/fisiopatologia , Placentação , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Fatores de Risco , Transdução de Sinais , Artéria Uterina/fisiopatologia , Remodelação Vascular , Rigidez Vascular
10.
Placenta ; 99: 45-49, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32755724

RESUMO

Vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and possible induction of pregnancy complications, including miscarriage, fetal malformations, fetal growth restriction and/or stillbirth, are serious concerns for pregnant individuals with COVID-19. According to clinical information, the incidence of vertical transmission of SARS-CoV-2 is limited to date. However, even if a neonate tests negative for SARS-CoV-2, frequent abnormal findings, including fetal and maternal vascular malperfusion, have been reported in cases of COVID-19-positive mothers. Primary receptor of SARS-CoV-2 is estimated as angiotensin-converting enzyme 2 (ACE2). It is highly expressed in maternal-fetal interface cells, such as syncytiotrophoblasts, cytotrophoblasts, endothelial cells, and the vascular smooth muscle cells of primary and secondary villi. However other route of transplacental infection cannot be ruled out. Pathological examinations have demonstrated that syncytiotrophoblasts are often infected with SARS-CoV-2, but fetuses are not always infected. These findings suggest the presence of a placental barrier, even if it is not completely effective. As the frequency and molecular mechanisms of intrauterine vertical transmission of SARS-CoV-2 have not been determined to date, intensive clinical examinations by repeated ultrasound and fetal heart rate monitoring are strongly recommended for pregnant women infected with COVID-19. In addition, careful investigation of placental samples after delivery by both morphological and molecular methods is also strongly recommended.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Placenta , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez/virologia , Antígenos Virais/análise , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Feminino , Doenças Fetais/epidemiologia , Doenças Fetais/virologia , Humanos , Recém-Nascido , Troca Materno-Fetal , Pandemias , Peptidil Dipeptidase A/análise , Placenta/irrigação sanguínea , Placenta/enzimologia , Placenta/virologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Trofoblastos/virologia
11.
Nat Rev Endocrinol ; 16(9): 479-494, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32601352

RESUMO

Pre-eclampsia and fetal growth restriction arise from disorders of placental development and have some shared mechanistic features. Initiation is often rooted in the maldevelopment of a maternal-placental blood supply capable of providing for the growth requirements of the fetus in later pregnancy, without exerting undue stress on maternal body systems. Here, we review normal development of a placental bed with a safe and adequate blood supply and a villous placenta-blood interface from which nutrients and oxygen can be extracted for the growing fetus. We consider disease mechanisms that are intrinsic to the maternal environment, the placenta or the interaction between the two. Systemic signalling from the endocrine placenta targets the maternal endothelium and multiple organs to adjust metabolism for an optimal pregnancy and later lactation. This signalling capacity is skewed when placental damage occurs and can deliver a dangerous pathogenic stimulus. We discuss the placental secretome including glycoproteins, microRNAs and extracellular vesicles as potential biomarkers of disease. Angiomodulatory mediators, currently the only effective biomarkers, are discussed alongside non-invasive imaging approaches to the prediction of disease risk. Identifying the signs of impending pathology early enough to intervene and ameliorate disease in later pregnancy remains a complex and challenging objective.


Assuntos
Retardo do Crescimento Fetal/fisiopatologia , Placentação/fisiologia , Pré-Eclâmpsia/fisiopatologia , Complicações na Gravidez/fisiopatologia , Biomarcadores , Decídua/fisiopatologia , Desenvolvimento Embrionário , Endométrio/fisiopatologia , Feminino , Desenvolvimento Fetal , Feto/irrigação sanguínea , Humanos , Placenta/irrigação sanguínea , Doenças Placentárias/fisiopatologia , Gravidez , Transdução de Sinais , Trofoblastos/fisiologia
12.
Am J Obstet Gynecol ; 223(5): 749.e1-749.e16, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32437666

RESUMO

BACKGROUND: The underlying pathomechanism in placenta-related selective fetal growth restriction in monochorionic diamniotic twin pregnancy is not known. OBJECTIVE: This study aimed to investigate any differences in placental transcriptomic profile between the selectively growth-restricted twins and the normally grown cotwins in monochorionic diamniotic twin pregnancies. STUDY DESIGN: This was a prospective study of monochorionic diamniotic twin pregnancies complicated by selective fetal growth restriction. Placental biopsy specimens were obtained from the subjects in the delivery suite. The placental transcriptome of the selectively growth-restricted twin was compared with that of the normally grown cotwin. This study was divided into 2 stages: (1) gene discovery phase in which placental tissues from 5 monochorionic diamniotic twin pregnancies complicated by selective fetal growth restriction plus 2 control twin pregnancies underwent transcriptome profiling, and transcriptome profiling was carried out using whole-genome RNA sequencing; and (2) validation phase in which placental tissues from 13 monochorionic diamniotic twin pregnancies with selective fetal growth restriction underwent RNA and protein validation. RNA and protein expression levels of candidate genes were determined using quantitative real-time polymerase chain reaction and immunohistochemistry staining. RESULTS: A total of 1429 transcripts were differentially expressed in the placentae of selectively growth-restricted twin pairs, where 610 were up-regulated and 819 were down-regulated. Endoplasmic reticulum lectin and mannose 6-phosphate receptor were consistently differentially up-regulated in all placentae of selectively growth-restricted twins. Quantitative real-time polymerase chain reaction and immunohistochemistry staining were used to validate the results (P<.05). CONCLUSION: The expression of endoplasmic reticulum lectin and mannose 6-phosphate receptor, which are important for angiogenesis and fetal growth, was significantly increased in the placentae of selectively growth-restricted twin of a monochorionic twin pair.


Assuntos
Desenvolvimento Fetal/genética , Retardo do Crescimento Fetal/genética , Lectinas/genética , Proteínas de Neoplasias/genética , Placenta/metabolismo , Gravidez de Gêmeos , Adulto , Âmnio , Estudos de Casos e Controles , Córion , Feminino , Perfilação da Expressão Gênica , Humanos , Hipóxia/genética , Imuno-Histoquímica , Neovascularização Fisiológica/genética , Placenta/irrigação sanguínea , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Receptor IGF Tipo 2/genética , Regulação para Cima
14.
Am J Clin Pathol ; 154(1): 23-32, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32441303

RESUMO

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


Assuntos
Infecções por Coronavirus/patologia , Placenta/patologia , Pneumonia Viral/patologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Betacoronavirus , Estudos de Casos e Controles , Feminino , Humanos , Pandemias , Placenta/irrigação sanguínea , Placenta/virologia , Gravidez , Terceiro Trimestre da Gravidez
15.
Int J Gynaecol Obstet ; 150(2): 248-253, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32415985

RESUMO

OBJECTIVES: To assess the role of the cerebro-placental ratio (CPR) in predicting adverse fetal outcomes among women with sickle cell disease (SCD). METHODS: A prospective cohort study at Korle-Bu Teaching Hospital, Accra, Ghana, between January and June 2016. Pregnant women with SCD at 34 gestational weeks or more underwent weekly fetal umbilical and middle cerebral artery Doppler assessment until delivery. Participants were categorized into two study arms based on CPR (<1.1 or ≥1.1). The primary outcome, a composite of adverse perinatal outcomes including intrauterine growth restriction, stillbirth, low birthweight, and neonatal intensive care unit admission, was compared between groups. RESULTS: Overall, 48 pregnant women with SCD were enrolled, and 5 had a fetus with CPR less than 1.1. Low CPR (<1.1) had a sensitivity and specificity of 29.4% and 100%, respectively, for predicting composite adverse perinatal outcomes. Sensitivity and specificity were, respectively, 100% and 93.5% for predicting stillbirth, and 40.2% and 97.4% for predicting low birthweight. Perinatal outcomes did not differ between the two major sickle cell genotypes (hemoglobin SS and hemoglobin SC). CONCLUSIONS: Among women with SCD, CPR less than 1.1 was associated with adverse perinatal outcomes, particularly low birthweight and stillbirth.


Assuntos
Anemia Falciforme/complicações , Artéria Cerebral Média/diagnóstico por imagem , Complicações Hematológicas na Gravidez , Resultado da Gravidez , Artérias Umbilicais/diagnóstico por imagem , Adulto , Feminino , Gana , Humanos , Recém-Nascido , Artéria Cerebral Média/embriologia , Placenta/irrigação sanguínea , Gravidez , Estudos Prospectivos , Fluxo Pulsátil , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Adulto Jovem
16.
Am J Physiol Regul Integr Comp Physiol ; 318(6): R1047-R1057, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32374620

RESUMO

Preeclampsia is a spontaneously occurring, pregnancy-specific syndrome that is clinically diagnosed by new onset hypertension and proteinuria. Epidemiological evidence describes an association between a history of preeclampsia and increased risk for cardiovascular disease in later life; however, the mechanism(s) driving this relationship are unclear. Our study aims to leverage a novel preeclampsia-like mouse model, the C1q-/- model, to help elucidate the acute and persistent vascular changes during and following a preeclampsia-like pregnancy. Female C57BL/6J mice were mated to C1q-/- male mice to model a preeclampsia-like pregnancy ("PE-like"), and the maternal cardiovascular phenotype (blood pressure, renal function, systemic glycocalyx, and ex vivo vascular function) was assessed in late pregnancy and postpartum at 6 and 10 mo of age. Uncomplicated, normotensive pregnancies (female C57BL/6J bred to male C57BL/6J mice) served as age-matched controls. In pregnancy, PE-like dams exhibited increased systolic and diastolic pressure during mid- and late gestation, renal dysfunction, fetal growth restriction, and reduced placental efficiency. Ex vivo wire myography studies of mesenteric arteries revealed severe pregnancy-specific endothelial-dependent and -independent vascular dysfunction. At 3 and 7 mo postpartum (6 and 10 mo old, respectively), hypertension resolved in PE-like dams, whereas mild vascular dysfunction persisted at 3 mo postpartum. In conclusion, the female C57BL/6J-by-male C57BL/6J C1q-/- model recapitulates many aspects of the human preeclampsia syndrome in a low-risk, wild-type female mouse. The pregnancy-specific phenotype results in systemic maternal endothelial-dependent and -independent vascular dysfunction that persists postpartum.


Assuntos
Complemento C1q/metabolismo , Pré-Eclâmpsia/metabolismo , Animais , Pressão Sanguínea/fisiologia , Complemento C1q/genética , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Knockout , Placenta/irrigação sanguínea , Pré-Eclâmpsia/genética , Gravidez
17.
Curr Opin Anaesthesiol ; 33(3): 368-373, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32324666

RESUMO

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


Assuntos
Anestesia/métodos , Doenças Fetais/cirurgia , Transfusão Feto-Fetal/cirurgia , Fetoscopia/métodos , Hérnias Diafragmáticas Congênitas/terapia , Placenta/irrigação sanguínea , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/terapia , Fetoscopia/efeitos adversos , Feto/cirurgia , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Doenças Placentárias/cirurgia , Gravidez , Cuidado Pré-Natal , Diagnóstico Pré-Natal
18.
Am J Physiol Regul Integr Comp Physiol ; 318(6): R1036-R1046, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320265

RESUMO

T-helper (TH)17s, IL-17, and cytolytic natural killer cells (cNKs) are increased in preeclampsia and contribute to the hypertension, inflammation, and fetal growth restriction that occurs in response to placental ischemia in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. As IL-17 stimulates NK cytotoxicity in vitro, we tested the hypothesis that IL-17 inhibition in RUPP rats would decrease cNK activation as a mechanism to improve maternal and fetal outcomes. On gestation day (GD) 14, rats undergoing RUPP received a miniosmotic pump infusing IL-17RC (100 pg/day), a soluble IL-17 receptor (RUPP + IL-17RC). On GD19, mean arterial pressure (MAP) was measured in normal pregnant (NP), RUPP, and RUPP + IL-17RC rats (n = 10-12/group), animals were euthanized, and blood and tissues were collected for analysis. MAP was 30% higher in RUPP compared with NP (P < 0.0001) and was 12% lower in RUPP + IL-17RC (P = 0.0007 vs. RUPP). Placental cytolytic NK cells were 132% higher in RUPP than in NP (P = 0.04 vs. NP) and were normalized in RUPP + IL-17RC (P = 0.03 vs. RUPP). Placental levels of TNF-α, a cNK-secreted cytokine, and macrophage inflammatory protein-3α (MIP-3α), a cNK chemokine, were higher in RUPP vs. NP and lower after IL-17 blockade. Placental VEGF was lower in RUPP vs. NP and was normalized in RUPP + IL-17RC. In vitro cytolytic activity of RUPP placental NKs was higher compared with NP and was blunted in RUPP + IL-17RC NKs. Finally, both fetal weight and placental weight were lower in RUPP compared with NP, and were improved in RUPP + IL-17RC. These data identify IL-17 as a mediator of cNK activation in response to placental ischemia during pregnancy.


Assuntos
Interleucina-17/metabolismo , Isquemia/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Placenta/irrigação sanguínea , Receptores de Interleucina-17/administração & dosagem , Animais , Pressão Arterial/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Mediadores da Inflamação/metabolismo , Isquemia/metabolismo , Placenta/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/metabolismo
19.
Transfusion ; 60(5): 1069-1077, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32315090

RESUMO

BACKGROUND: Phlebotomy is among the main determinants of anemia of prematurity. Blood sparing policies endorsed umbilical cord blood (here called placental) as an alternative source for laboratory testing. Little is known on the suitability of placental blood to evaluate neonatal hemostasis of newborn infants. We aimed to compare the hemostatic profile of paired placental and infant venous blood, by means of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, protein C, thromboelastography (TEG) and thrombin generation assay (TGA). STUDY DESIGN: This was an observational single-center study. METHODS: We collected at birth venous citrated blood from both placental and infant venous source and performed PT, APTT, fibrinogen, antithrombin, protein C, TEG (reaction time-R; kinetics-K alpha angle-α, maximum amplitude-MA and lysis at 30 minutes-LY30), and TGA (endogenous thrombin potential-ETP). RESULTS: We enrolled 60 neonates with a median gestational age (range) of 37 weeks (28+1 -41) and birth-weight 2417 g (950-4170). Based on TEG and TGA, placental blood showed a procoagulant imbalance as indicated by lower median R (4.0 vs. 6.1 min; p < 0.001) and K (1.3 vs. 2.2 min; p < 0.001); higher α-angle (69.7 vs. 57.4°; p < 0.001) and ETP (1260 vs. 1078; p = 0.002) than those observed for infant venous blood. PT and APTT did not differ significantly between the two groups. CONCLUSIONS: While placental and neonatal blood samples are equally suitable to measure the standard coagulation tests PT and APTT, placental blood leads to a procoagulant imbalance when testing is performed with TEG or TGA. These effects should be considered when interpreting results stemming from investigation of neonatal hemostasis.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Hemostasia/fisiologia , Doenças do Recém-Nascido/diagnóstico , Triagem Neonatal/métodos , Placenta/irrigação sanguínea , Transtornos da Coagulação Sanguínea/sangue , Testes de Coagulação Sanguínea , Feminino , Sangue Fetal/fisiologia , Fibrinogênio/análise , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Recém-Nascido/sangue , Masculino , Tempo de Tromboplastina Parcial , Parto/sangue , Flebotomia/métodos , Flebotomia/normas , Gravidez , Tempo de Protrombina , Reprodutibilidade dos Testes , Trombina/análise
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