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1.
BMC Pregnancy Childbirth ; 21(1): 760, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758757

RESUMO

BACKGROUND: Infection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn. CASE PRESENTATION: We report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma. CONCLUSIONS: This case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women.


Assuntos
COVID-19/terapia , Oxigenação por Membrana Extracorpórea/métodos , Placenta/patologia , Complicações Infecciosas na Gravidez/terapia , Adulto , COVID-19/diagnóstico , Cesárea , Feminino , Humanos , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Segundo Trimestre da Gravidez , Resultado do Tratamento
2.
Diagn Pathol ; 16(1): 88, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602071

RESUMO

INTRODUCTION: COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, is a severe systemic thrombotic syndrome that emerged in 2019, with an ensuing pandemic. To evaluate the impact of this disease on placental tissue and perinatal outcome, histological, immunohistochemical and ultrastructural analyses of placental tissue were performed for five cases of pregnant women with COVID-19. CASE REPORTS: All five pregnant women in this series developed COVID-19 in late pregnancy. Two patients experienced respiratory distress, and computed tomography revealed signs of pneumonia, with bilateral involvement, multiple lobular and subsegmental areas of consolidation and ground-glass opacities. Histological studies of placental tissue revealed the presence of slight signs of maternal vascular underperfusion (MVUs) or foetal vascular underperfusion (FVUs) lesions and mild inflammatory lesions. CD15 immunoreactivity in the placental tissue was low in all cases, demonstrating that in these cases there was not severe foetal hypoxia/asphyxia risk for newborns or distal vascular immaturity. In all cases examined, ultrastructural analyses showed spherical-like coronavirus particles with an electron intermediate-density core as well as projections from the surface as spike-like structures in the syncytiotrophoblasts. At term, all of the women delivered newborns who were negative for SARS-CoV-2 by nasopharyngeal testing in their first day of life. All newborns were exclusively breastfed and were discharged on the 3rd day of life. CONCLUSIONS: In conclusion, placental patterns in pregnancy due to COVID-19 in the late stage of gestation indicate no evidence of vertical trans-placental SARS-CoV-2 transmission or a significant impact on the perinatal outcome of newborns, in both mild and more severe cases.


Assuntos
COVID-19/diagnóstico por imagem , Transmissão Vertical de Doenças Infecciosas , Pandemias , Complicações Infecciosas na Gravidez , SARS-CoV-2/fisiologia , Adulto , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Feminino , Humanos , Recém-Nascido , Placenta/diagnóstico por imagem , Placenta/patologia , Placenta/virologia , Gravidez , Resultado da Gravidez , Tomografia Computadorizada por Raios X , Trofoblastos/patologia , Trofoblastos/virologia
3.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34638542

RESUMO

Preeclampsia is a pregnancy disorder associated with shallow placentation, forcing placental cells to live in hypoxic conditions. This activates the transcription factor kappa B (NFκB) in maternal and placental cells. Although the role of NFκB in preeclampsia is well documented, its mechanism of activation in trophoblastic cells has been never studied. This study investigates the mechanism of NFκB activation in a first trimester trophoblastic cell line (HTR8/SVneo) stimulated by a medium containing serum from preeclamptic (PE) or normotensive (C) women in hypoxic (2% O2) or normoxic (8% O2) conditions. The results indicate that in HTR8/SVneo cells, the most widely studied NFκB pathways, i.e., canonical, non-canonical and atypical, are downregulated in environment PE 2% O2 in comparison to C 8% O2. Therefore, other pathways may be responsible for NFκB activation. One such pathway depends on the activation of NFκB by the p53/RSK1 complex through its phosphorylation at Serine 536 (pNFκB Ser536). The data generated by our study show that inhibition of the p53/RSK1 pathway by p53-targeted siRNA results in a depletion of pNFκB Ser536 in the nucleus, but only in cells incubated with PE serum at 2% O2. Thus, the p53/RSK1 complex might play a critical role in the activation of NFκB in trophoblastic cells and preeclamptic placentas.


Assuntos
NF-kappa B/metabolismo , Pré-Eclâmpsia/patologia , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Trofoblastos/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Hipóxia Celular/fisiologia , Linhagem Celular , Ativação Enzimática/genética , Feminino , Humanos , Placenta/patologia , Gravidez , Interferência de RNA , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética
4.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638773

RESUMO

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-related condition characterized by increased maternal circulating bile acids (BAs) having adverse fetal effects. We investigated whether the human placenta expresses specific regulation patterns to prevent fetal exposition to harmful amounts of BAs during ICP. Using real-time quantitative PCR, we screened placentae from healthy pregnancies (n = 12) and corresponding trophoblast cells (n = 3) for the expression of 21 solute carriers and ATP-binding cassette transporter proteins, all acknowledged as BA- and/or cholestasis-related genes. The placental gene expression pattern was compared between healthy women and ICP patients (n = 12 each). Placental SLCO3A1 (OATP3A1) gene expression was significantly altered in ICP compared with controls. The other 20 genes, including SLC10A2 (ASBT) and EPHX1 (EPOX, mEH) reported for the first time in trophoblasts, were comparably abundant in healthy and ICP placentae. ABCG5 was undetectable in all placentae. Placental SLC10A2 (ASBT), SLCO4A1 (OATP4A1), and ABCC2 mRNA levels were positively correlated with BA concentrations in ICP. Placental SLC10A2 (ASBT) mRNA was also correlated with maternal body mass index. We conclude that at the transcriptional level only a limited response of BA transport systems is found under ICP conditions. However, the extent of the transcriptional response may also depend on the severity of the ICP condition and the magnitude by which the maternal BA levels are increased.


Assuntos
Proteínas de Transporte/biossíntese , Colestase Intra-Hepática/metabolismo , Regulação da Expressão Gênica , Glicoproteínas de Membrana/biossíntese , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Colestase Intra-Hepática/patologia , Feminino , Humanos , Placenta/patologia , Gravidez , Complicações na Gravidez/patologia
5.
Front Immunol ; 12: 743022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603330

RESUMO

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.


Assuntos
COVID-19/patologia , Placenta/patologia , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , Aborto Espontâneo/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Feminino , Retardo do Crescimento Fetal/virologia , Humanos , Troca Materno-Fetal/fisiologia , Gravidez , SARS-CoV-2/patogenicidade , Serina Endopeptidases/metabolismo , Natimorto
6.
Viruses ; 13(9)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34578466

RESUMO

(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/fisiologia , Adulto , Biópsia , COVID-19/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Transmissão Vertical de Doenças Infecciosas , Placenta/patologia , Placenta/virologia , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Resultado da Gravidez , Estudos Retrospectivos , Adulto Jovem
8.
Rev. méd. Urug ; 37(3): e37314, set. 2021. graf
Artigo em Espanhol | LILACS, BNUY | ID: biblio-1341562

RESUMO

Resumen: La secuencia de perfusión arterial reversa (TRAP) es una complicación muy poco frecuente y grave de los embarazos gemelares monocoriónicos. Generalmente ocurre cuando el corazón de un gemelo de apariencia normal sirve como bomba para uno o más gemelos dismórficos cuya cabeza, órganos torácicos y extremidades superiores no se desarrollan completamente o no se desarrollan en absoluto y, por lo tanto, carecen de actividad cardíaca. La arquitectura placentaria vascular anómala provoca un cambio en el flujo arterial hacia el gemelo acardíaco. Los mecanismos fisiopatológicos exactos que conducen a este fenómeno devastador no se conocen bien. Compartiremos el caso clínico de una paciente de 19 años, cursando un embarazo gemelar monocorial monoamniótico, en que realizamos diagnóstico de TRAPS, y realizamos la coagulación laser de la arteria nutricia del feto acárdico.


Abstract: Twin reversed arterial perfusion sequence (TRAPS) is rather an unusual and severe complication of monochorionic twin pregnancies. It usually occurs when the normal-appearance heart of a twin acts as a pump for one or more dysmorphic twins whose head, thoracic organs and upper limbs fail to totally develop or do not develop at all and thus, have no cardiac activity. The abnormal vascular architecture at the placenta changes the arterial flow towards the acardiac twin. The exact pathophysiological mechanisms that result in this devastating phenomenon are still unknown. The study presents the clinical case of a 19-year- old patient pregnant with monoamniotic, monochorionic twins and a diagnosis of TRAPS, treated by laser coagulation of the acardiac twin's umbilical cord.


Resumo: A seqüência reversa de perfusão arterial (TRAPS) é uma complicação muito rara e grave de gestações gemelares monocoriônicas. Geralmente ocorre quando o coração de um gêmeo de aparência normal serve como uma bomba para um ou mais gêmeos dismórficos cuja cabeça, órgãos torácicos e membros superiores não se desenvolvem totalmente ou não se desenvolvem e, portanto, não têm atividade cardíaca. A arquitetura vascular placentária anormal causa uma mudança no fluxo arterial para o gêmeo acardíaco. Os mecanismos fisiopatológicos exatos que levam a esse fenômeno devastador não são bem compreendidos. Descrevemos o caso clínico de uma paciente de 19 anos, portadora de gestação gemelar monocoriônica monoamniótica, na qual fizemos o diagnóstico de TRAPS e realizamos coagulação a laser da artéria nutritiva do feto acardíaco.


Assuntos
Humanos , Feminino , Gravidez , Adulto , Fotocoagulação a Laser , Coração Fetal/anormalidades , Transfusão Feto-Fetal , Placenta/patologia , Artérias Umbilicais/cirurgia , Gravidez de Gêmeos
9.
Placenta ; 115: 37-44, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34537470

RESUMO

INTRODUCTION: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology. METHODS: Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded. RESULTS: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index. DISCUSSION: Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes.


Assuntos
COVID-19 , Doenças Placentárias/etiologia , Complicações Infecciosas na Gravidez , Estresse Psicológico/complicações , Adolescente , Adulto , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/psicologia , Canadá/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Relações Materno-Fetais/psicologia , Pessoa de Meia-Idade , Pandemias , Placenta/patologia , Placenta/virologia , Doenças Placentárias/epidemiologia , Doenças Placentárias/patologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/psicologia , Resultado da Gravidez/epidemiologia , Resultado da Gravidez/psicologia , Angústia Psicológica , SARS-CoV-2/fisiologia , Estresse Psicológico/etiologia , Estresse Psicológico/patologia , Reino Unido/epidemiologia , Adulto Jovem
10.
Chem Biol Interact ; 347: 109618, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34364836

RESUMO

The toxicity of hybrid nanoparticles, consisting of non-toxic components, zirconium dioxide nanoparticles (ZrO2 NPs), and caffeic acid (CA), was examined against four different cell lines (HTR-8 SV/Neo, JEG-3, JAR, and HeLa). Stable aqueous ZrO2 sol, synthesized by forced hydrolysis, consists of 3-4 nm in size primary particles organized in 30-60 nm in size snowflake-like particles, as determined by transmission electron microscopy and direct light scattering measurements. The surface modification of ZrO2 NPs with CA leads to the formation of an interfacial charge transfer (ICT) complex followed by the appearance of absorption in the visible spectral range. The spectroscopic observations are complemented with the density functional theory calculations using a cluster model. The ZrO2 NPs and CA are non-toxic against four different cell lines in investigated concentration range. Also, ZrO2 NPs promote the proliferation of HTR-8 SV/Neo, JAR, and HeLa cells. On the other hand, hybrid ZrO2/CA NPs induced a significant reduction of the viability of the JEG-3 cells (39 %) for the high concentration of components (1.6 mM ZrO2 and 0.4 mM CA).


Assuntos
Ácidos Cafeicos/toxicidade , Nanopartículas Metálicas/toxicidade , Placenta/efeitos dos fármacos , Zircônio/toxicidade , Ácidos Cafeicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Feminino , Humanos , Nanopartículas Metálicas/química , Modelos Químicos , Tamanho da Partícula , Placenta/patologia , Gravidez , Testes de Toxicidade , Zircônio/química
11.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360662

RESUMO

A well-functioning placenta is crucial for normal gestation and regulates the nutrient, gas, and waste exchanges between the maternal and fetal circulations and is an important endocrine organ producing hormones that regulate both the maternal and fetal physiologies during pregnancy. Placental insufficiency is implicated in spontaneous preterm birth (SPTB). We proposed that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may ultimately result in SPTB. To explore our hypothesis, we performed a RNA-seq study in male and female placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation) to assess the alterations in the gene expression profiles. We focused exclusively on Black women (cases and controls), who are at the highest risk of SPTB. Six hundred and seventy differentially expressed genes were identified in male SPTB placentas. Among them, 313 and 357 transcripts were increased and decreased, respectively. In contrast, only 61 differentially expressed genes were identified in female SPTB placenta. The ingenuity pathway analysis showed alterations in the genes and canonical pathways critical for regulating inflammation, oxidative stress, detoxification, mitochondrial function, energy metabolism, and the extracellular matrix. Many upstream regulators and master regulators important for nutrient-sensing and metabolism were also altered in SPTB placentas, including the PI3K complex, TGFB1/SMADs, SMARCA4, TP63, CDKN2A, BRCA1, and NFAT. The transcriptome was integrated with published human placental metabolome to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the transcriptome were identified in SPTB placentas with fetal sex disparities. Altered energy metabolism, mitochondrial function, inflammation, and detoxification may underly the mechanisms of placental dysfunction in SPTB.


Assuntos
Metabolismo Energético , Inflamação/patologia , Doenças Placentárias/patologia , Placenta/patologia , Nascimento Prematuro/patologia , Transcriptoma , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Masculino , Placenta/imunologia , Placenta/metabolismo , Doenças Placentárias/genética , Doenças Placentárias/imunologia , Doenças Placentárias/metabolismo , Gravidez , Nascimento Prematuro/genética , Nascimento Prematuro/imunologia , Nascimento Prematuro/metabolismo , Fatores Sexuais
12.
Biomed Res Int ; 2021: 9933389, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368361

RESUMO

Khat (Catha edulis Forsk) is a plant consumed by many people in Eastern Africa, including Ethiopia, and Southern Arabia to be stimulated. There are several human and animal studies on khat that provide information about its toxic effects. However, the potential toxic effects of khat on embryos and fetuses have not been elucidated. The aim of the present study was to investigate the embryotoxic and fetotoxic effects of khat exposure during the earliest period of gestation in rats. Pregnant Wistar albino rats were treated with khat extract at 250, 500, and 750 mg/kg doses from day 6 through day 12 of gestation. The treatment was delivered by gavage. Embryos and fetuses were recovered on gestational day 12 or day 20, respectively, and were quantitatively and qualitatively assessed for developmental anomalies. Placentae from the treatment and control groups were investigated for histopathological effects. Results of the present study showed that khat exposure during pregnancy had dose-dependent toxic effects in rat embryos and fetuses. Prenatal growth retardation such as reduced fetal weight and crown-rump length was observed in near-term fetuses, especially, in animals treated with the highest dose of khat (p < 0.05). Growth retardation and developmental anomalies were also observed in day 12 embryos of khat-treated rats. Maternal weight gain of the khat-treated group was also significantly lower than the control group. Cytolysis, decidual hypoplasia, and atrophy were observed in the placenta of the khat-treated rats. Findings of the present study revealed, for the first time, that exposure of pregnant rat to crude extract of khat causes embryotoxic and fetotoxic effects.


Assuntos
Catha/química , Embrião de Mamíferos/patologia , Feto/patologia , Testes de Toxicidade , Animais , Desenvolvimento Embrionário , Feminino , Feto/embriologia , Placenta/patologia , Gravidez , Resultado da Gravidez , Ratos Wistar
13.
Ann Clin Lab Sci ; 51(4): 570-572, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452898

RESUMO

COVID-19 has affected patients of all ages and demographics, not excluding pregnant women. The effects of COVID-19 on pregnant women are still largely unknown. Several adverse perinatal outcomes have been reported in COVID-19-positive pregnant women, including pre-eclampsia, miscarriage, pre-term labor, and stillbirth. Histopathological examination of COVID-19 placentas can contribute significant data regarding maternal and fetal health and can elucidate more findings in this novel disease. A 23-year-old female with morbid obesity and scant antenatal care presented to the emergency department complaining of shortness of breath and fever; she was found to be positive for COVID-19. Grossly, her placenta showed no abnormalities. Histological examination of her placenta showed chronic lymphoplasmacytic deciduitis, villous fibrosis, loss of capillarization, extravasation of erythrocytes, chorangiosis, and thrombosis of upstream stem vessels, including large fetal vessels on the chorionic plate. These changes were deemed to be consistent with fetal thrombotic vasculopathy (FTV). In conclusion, this case of FTV in the placenta of a patient with COVID-19 is a significant finding, as it can be critical to clinicians in the management of prenatal care for expecting mothers during this pandemic.This case was presented at the annual meeting of the Association of Clinical Scientists (ACS) on May 13, 2021.


Assuntos
COVID-19/complicações , Doenças Fetais/patologia , Feto/patologia , Doenças Placentárias/patologia , Placenta/patologia , SARS-CoV-2/isolamento & purificação , Trombose/patologia , Adulto , COVID-19/transmissão , COVID-19/virologia , Feminino , Doenças Fetais/virologia , Feto/virologia , Humanos , Placenta/virologia , Doenças Placentárias/virologia , Gravidez , Prognóstico , Trombose/virologia , Adulto Jovem
14.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360849

RESUMO

Gestational Diabetes Mellitus (GDM) is a transitory metabolic condition caused by dysregulation triggered by intolerance to carbohydrates, dysfunction of beta-pancreatic and endothelial cells, and insulin resistance during pregnancy. However, this disease includes not only changes related to metabolic distress but also placental immunoendocrine adaptations, resulting in harmful effects to the mother and fetus. In this review, we focus on the placenta as an immuno-endocrine organ that can recognize and respond to the hyperglycemic environment. It synthesizes diverse chemicals that play a role in inflammation, innate defense, endocrine response, oxidative stress, and angiogenesis, all associated with different perinatal outcomes.


Assuntos
Diabetes Gestacional , Células Endoteliais , Feto , Hiperglicemia , Placenta , Diabetes Gestacional/imunologia , Diabetes Gestacional/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Feto/imunologia , Feto/metabolismo , Humanos , Hiperglicemia/imunologia , Hiperglicemia/metabolismo , Placenta/imunologia , Placenta/metabolismo , Placenta/patologia , Gravidez
15.
Nutrients ; 13(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34444747

RESUMO

Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.


Assuntos
Fertilização , Sangue Fetal/metabolismo , Nutrientes , Placenta/metabolismo , Terceiro Trimestre da Gravidez , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Sistema A de Transporte de Aminoácidos/metabolismo , Apoptose , Proliferação de Células , Feminino , Transportador de Glucose Tipo 1/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Placenta/patologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/etiologia , Técnicas de Reprodução Assistida/efeitos adversos , Injeções de Esperma Intracitoplásmicas/métodos
16.
Viruses ; 13(8)2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34452534

RESUMO

BACKGROUND: Although the risk for transplacental transmission of SARS-CoV-2 is rare, placental infections with adverse functional consequences have been reported. This study aims to analyse histological placental findings in pregnancies complicated by SARS-CoV-2 infection and investigate its correlation with clinical symptoms and perinatal outcomes. We want to determine which pregnancies are at-risk to prevent adverse pregnancy outcomes related to COVID-19 in the future. METHODS: A prospective, longitudinal, multicentre, cohort study. All pregnant women presenting between April 2020 and March 2021 with a nasopharyngeal RT-PCR-confirmed SARS-CoV-2 infection were included. Around delivery, maternal, foetal and placental PCR samples were collected. Placental pathology was correlated with clinical maternal characteristics of COVID-19. RESULTS: Thirty-six patients were included, 33 singleton pregnancies (n = 33, 92%) and three twin pregnancies (n = 3, 8%). Twenty-four (62%) placentas showed at least one abnormality. Four placentas (4/39, 10%) showed placental staining positive for the presence of SARS-CoV-2 accompanied by a unique combination of diffuse, severe inflammatory placental changes with massive perivillous fibrin depositions, necrosis of syncytiotrophoblast, diffuse chronic intervillositis, and a specific, unprecedented CD20+ B-cell infiltration. This SARS-CoV-2 placental signature seems to correlate with foetal distress (75% vs. 15.6%, p = 0.007) but not with the severity of maternal COVID-19 disease. CONCLUSION: We describe a unique placental signature in pregnant patients with COVID-19, which has not been reported in a historical cohort. We show that the foetal environment can be seriously compromised by disruption of placental function due to local, devastating SARS-CoV-2 infection. Maternal clinical symptoms did not predict the severity of the SARS-CoV-2-related placental signature, resulting in a lack of adequate identification of maternal criteria for pregnancies at risk. Close foetal monitoring and pregnancy termination in case of foetal distress can prevent adverse pregnancy outcomes due to COVID-19 related placental disease.


Assuntos
COVID-19/patologia , Doenças Placentárias/patologia , Placenta/patologia , Complicações Infecciosas na Gravidez/patologia , Adulto , COVID-19/fisiopatologia , COVID-19/virologia , Feminino , Sofrimento Fetal/fisiopatologia , Humanos , Estudos Longitudinais , Placenta/fisiopatologia , Placenta/virologia , Doenças Placentárias/fisiopatologia , Doenças Placentárias/virologia , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Trofoblastos/patologia
17.
Curr Issues Mol Biol ; 43(2): 831-844, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34449559

RESUMO

Previous studies assessed the involvement and impact of periodontal bacteria in preeclamptic women with chronic periodontitis. To explore further, the current study aimed to associate periodontal viruses and bacteria with mir155 levels in placental tissues of preeclamptic women with generalized chronic periodontitis. Four-hundred 45 pregnant women, 18-35 years of age, were selected and divided into four groups (controls, A, B, and C) where the Controls included 145 systemically and periodontally healthy pregnant women Group A-100 systemically healthy pregnant women with chronic periodontitis, Group B- 100 preeclamptic women with chronic periodontitis, Group C- 100 preeclamptic women without chronic periodontitis. Age, BMI, SES, and periodontal parameters such as PI, BOP, PPD, and CAL were noted. Periodontal pathogens such as Tf, Td, Pg, Pi, Fn, HSV, EBV, and HCMV were tested in subgingival plaque, placental tissues, and mir155. We observed that PI, BOP, PPD, CAL, Tf, and EBV were highly significant in Group B. We found a higher number of periodontal bacteria, viruses, and mir 155 in Group B showing a higher risk of preeclampsia. More genetic studies in this field are advised to ascertain the role of periodontopathogens and mir 155 in preeclampsia and periodontal inflammation. What is already known on this subject? Periodontal diseases pose an increased risk of developing preeclampsia and delivering preterm and/or low-birth-weight babies. What do the results of this study add? Periodontal variables such as PI, pocket depth, BOP, and clinical attachment levels, were found to be increased in the preeclamptic women with chronic periodontitis. The significant difference was seen in the relative fold expression of mir155 with higher gene expression of mir155 in groups B and A as compared to group C and controls. What are the implications of these findings for clinical practice and/or further research? In our study, mir155 correlation with the periodontal parameters and periodontal pathogens further strengthen the evidence of periodontal inflammation as a risk of preeclampsia in pregnant women especially when associated with chronic periodontitis. mir155 can be considered to be one of the genetic biomarkers and can be used as a diagnostic tool for the early detection of PE.


Assuntos
Bactérias/patogenicidade , Periodontite Crônica/genética , Periodontite Crônica/microbiologia , MicroRNAs/genética , Placenta/patologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/microbiologia , Vírus/patogenicidade , Adolescente , Adulto , Estudos de Casos e Controles , Periodontite Crônica/complicações , Feminino , Humanos , Recém-Nascido , Placenta/metabolismo , Pré-Eclâmpsia/etiologia , Gravidez , Adulto Jovem
18.
Sci Rep ; 11(1): 15743, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344912

RESUMO

Pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and neonatal health outcomes, with differences in risk observed between sexes. Given that the placenta is a sexually dimorphic organ and critical regulator of development, examining differences in placental mRNA and miRNA expression in relation to pre-pregnancy BMI may provide insight into responses to maternal BMI in utero. Here, genome-wide mRNA and miRNA expression levels were assessed in the placentas of infants born extremely preterm. Differences in expression were evaluated according to pre-pregnancy BMI status (1) overall and (2) in male and female placentas separately. Overall, 719 mRNAs were differentially expressed in relation to underweight status. Unexpectedly, no genes were differentially expressed in relation to overweight or obese status. In male placentas, 572 mRNAs were associated with underweight status, with 503 (70%) overlapping genes identified overall. Notably, 43/572 (8%) of the mRNAs associated with underweight status in male placentas were also gene targets of two miRNAs (miR-4057 and miR-128-1-5p) associated with underweight status in male placentas. Pathways regulating placental nutrient metabolism and angiogenesis were among those enriched in mRNAs associated with underweight status in males. This study is among the first to highlight a sexually dimorphic response to low pre-pregnancy BMI in the placenta.


Assuntos
Índice de Massa Corporal , MicroRNAs/genética , Obesidade/fisiopatologia , Placenta/patologia , RNA Mensageiro/metabolismo , Caracteres Sexuais , Magreza/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Placenta/metabolismo , Gravidez , RNA Mensageiro/genética , Adulto Jovem
19.
Arch Pathol Lab Med ; 145(11): 1341-1349, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34338723

RESUMO

CONTEXT.­: Case reports and rare case series have demonstrated variable placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In rare small studies demonstrating infection of the placental parenchyma, histologic manifestations have included variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and syncytiotrophoblast necrosis. OBJECTIVE.­: To characterize the placental pathologic features of SARS-CoV-2-infected placentas, irrespective of fetal-maternal transmission, and to examine the frequency of C4d activation in such cases. DESIGN.­: A retrospective study of 7 placentas from mothers with active SARS-CoV-2 infection and placental infection as demonstrated by RNA in situ hybridization was conducted. RESULTS.­: There were 6 placentas from live-born neonates (5 singletons, 1 nonfused diamniotic-dichorionic twin placenta), and 1 was from a stillbirth. A total of 5 of the 8 neonates (including the stillbirth) tested negative for SARS-CoV-2, and all were negative for neonatal infection. The remaining 3 neonates were well at time of discharge. All placentas were positive for SARS-CoV-2 infection by RNA in situ hybridization and demonstrated variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. Three cases demonstrated features of fetal vascular malperfusion. CD68 highlighted intervillous histiocytes. C4d expression was present along the villous borders in 6 of 7 cases. CONCLUSIONS.­: SARS-CoV-2 placentitis is defined by the triad of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. The features may occur in cases without confirmed transplacental transmission. The damage caused by SARS-CoV-2 placentitis is likely mediated by complement activation.


Assuntos
COVID-19/diagnóstico , Doenças Placentárias/diagnóstico , Placenta/patologia , Placenta/virologia , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/metabolismo , COVID-19/imunologia , COVID-19/patologia , COVID-19/transmissão , Teste para COVID-19 , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Ativação Linfocitária , Masculino , Doenças Placentárias/imunologia , Doenças Placentárias/patologia , Doenças Placentárias/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , Natimorto
20.
Indian J Pathol Microbiol ; 64(3): 568-570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34341275

RESUMO

In the case of single fetal demise in a twin gestation, the fate of the dead twin, surviving twin, and mother depend on the exact time of fetal demise. The dead twin may "vanish" in a first trimester death; form a mummified "fetus papyraceus" due to mechanical compression in the second trimester or show changes of maceration in the third trimester. Hematological complications in the mother and neurological complications in the surviving twin may ensue in later trimester deaths. We report a unique case of an undiagnosed fetus papyraceus incidentally detected in an otherwise normal placenta. Identification of such cases is essential due to the occurrence of severe complications in some of the cases, medicolegal implications for the caregivers, and to improve the understanding of embryological development and fetal demise in twin or multiple gestations.


Assuntos
Morte Fetal , Placenta/patologia , Gêmeos , Adulto , Feminino , Técnicas Histológicas , Humanos , Gravidez , Complicações na Gravidez
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