Utilização da Placenta Humana na Cicatrização de Úlceras nos Pés de Pessoas com Diabetes: Revisão Integrativa / Use of the Human Placenta in the Healing of Foot Ulcers in People With Diabetes: Integrative Review / Uso De la Placenta Humana en la Cicatrización de las Úlceras del Pie en Personas con Diabetes: Revisión Integradora

Objetivo:Identificar na literatura as contribuições da utilização da placenta humana na cicatrização de úlceras nos pés de pessoas com diabetes. Método: Estudo de revisão integrativa realizado por meio da busca de artigos na Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, National Library of Medicine (PubMed), Web of Science e Scopus, com a utilização das estratégias de busca: Placenta AND "Pé diabético" e Placenta AND "Diabetic foot". Resultados: A busca inicial resultou em 148 artigos. Após aplicação dos critérios de inclusão e exclusão, obteve-se amostra final de 12 artigos. Observou-se que a placenta tem potencial de promover a melhora do tecido de granulação e a circulação periférica, maior repitelização, redução na área da ferida, com uso majoritário de aloenxerto de membranas placentária e amniótica criopreservadas. Conclusão: A placenta humana é um material biológico rico em nutrientes que apresentou potencial para contribuir com o reparo tecidual de úlceras nos pés de pessoas com diabetes em menor período de tempo.

Objective:To identify in the literature the contributions of the use of the human placenta in the healing of foot ulcers in people with diabetes. Method: An integrative review study carried out by searching articles in Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, National Library of Medicine (PubMed), Web of Science and Scopus, using the search strategies: Placenta AND "Diabetic foot" and Placenta AND "Diabetic Foot". Results: The initial search resulted in 148 articles. After applying the inclusion and exclusion criteria, a final sample of 12 articles was obtained. It was observed that the placenta has the potential to promote the improvement of granulation tissue and peripheral circulation, greater epithelialization, and reduction in the wound area, with the majority use of cryopreserved placental and amniotic membrane allograft. Conclusion: The human placenta is a nutrient-rich biological material that has the potential to contribute to the tissue repair of foot ulcers in people with diabetes in a shorter period of time.

Objetivo:Identificar en la literatura las contribuciones del uso de la placenta humana en la cicatrización de las úlceras del pie en personas con diabetes. Método: Estudio de revisión integradora, realizado mediante búsqueda de artículos en LILACS, SCIELO, CINAHL, Cochrane Library, PubMed, Web of Science y Scopus, utilizando las estrategias de búsqueda: Placenta AND "Diabetic foot" y Placenta AND "Diabetic Foot". Resultados: La búsqueda inicial resultó en 148 artículos. Tras aplicar los criterios de inclusión y exclusión, se obtuvo una muestra final de 12 artículos. Se observó que la placenta tiene el potencial de promover la mejoría del tejido de granulación y circulación periférica, mayor reepitelización, reducción del área de la herida, con uso mayoritario de aloinjerto de placenta y membrana amniótica criopreservados. Conclusión: La placenta humana es un material biológico rico en nutrientes que tiene el potencial de contribuir a la reparación tisular de las úlceras del pie en personas con diabetes en un período de tiempo más corto.

Whole-transcriptome sequencing analysis of placental differential miRNA expression profile in Down syndrome / 南方医科大学学报

OBJECTIVE@#To identify new biomarkers and molecular pathogenesis of Down syndrome (DS) by analyzing differentially expressed miRNAs in the placentas and their biological pathways.@*METHODS@#Whole transcriptome sequencing was used to identify the differentially expressed miRNAs in DS (n=3) and normal placental samples (n=3) diagnosed by prenatal diagnosis. The target genes were predicted using miRWalk, Targetscan and miRDB, and GO and KEGG pathway analyses were performed for gene enrichment studies.@*RESULTS@#We identified a total of 82 differentially expressed miRNAs in the placental tissues of DS, including 29 up-regulated miRNAs (fold change ≥2, P < 0.05) and 15 down-regulated miRNAs (fold change ≥2, P < 0.05), among which 10 miRNAs with relatively high expression abundance were selected for further analysis, including 4 up-regulated and 6 down-regulated miRNAs. These selected miRNAs shared the common target genes BTBD3 and AUTS2, both of which were associated with neurodevelopment. GO analysis showed that the target genes of the selected miRNAs were mainly enriched in protein binding, hydrolytic enzymes, metal ion binding protein combining, transferase activity, nucleotide, cytoplasmic constituents, nucleus composition, transcriptional regulation, RNA metabolism regulation, DNA-dependent RNA polymerase Ⅱ promoter transcriptional regulation, eye development, and sensory organ development. KEGG enrichment analysis showed that the target genes of these differentially expressed miRNAs were involved in the signaling pathways including tumor-related signaling pathway, PI3K-Akt signaling pathway, Ras signaling pathway, Rap1 signaling pathway, cytoskeletal regulatory signaling pathway, purine metabolization-related signaling pathway and P53 signaling pathway.@*CONCLUSION@#The differentially expressed miRNAs may play important roles in placental damage and pregnancy pathology in DS and provide clues for the prevention and treatment of mental retardation-related diseases.

Autopsies and placental examinations of perinatal fetal deaths: a clinicopathological analysis of 105 cases / 中华病理学杂志

Objective: To summarize the clinicopathological factors related to perinatal fetal death and to evaluate importance of fetal autopsy and placental pathology. Methods: The clinicopathological data of 105 perinatal fetal deaths in Beijing Haidian Maternal and Child Health Hospital from November 2012 to December 2020 were retrospectively analyzed. Relevant literature was also reviewed. Results: The maternal age of the deceased fetuses ranged from 22 to 43 years with the average (31.35±4.04 years), and the gestational weeks were 28-40+6 weeks. Among them, 101 were singleton cases and 4 twin cases. 103 fetuses died in uterus and 2 died during delivery. Relevant factors analysis of the 105 perinatal fetal deaths showed that 86 cases (81.9%, 86/105) were related to umbilical cord/placental abnormality, 10 cases (9.5%, 10/105) uterine infection, 6 cases (5.7%, 6/105) fetal factors, 1 case was fetal maternal blood transfusion syndrome, 1 case twin blood transfusion syndrome, and 1 case died of complete uterine rupture. Among the 86 cases related to umbilical cord/placental abnormality, the diagnosis was most often based on the gross examination of placenta. The most common cause of death was umbilical cord torsion with thin root, followed by placental abruption, tight umbilical cord winding, vascular rupture and umbilical cord true knot. The morphology of placenta revealed mainly functional changes. Among the 10 cases related to intrauterine infections, the placenta generally showed lobular placental edema. The morphological characteristics of ascending infection were mainly acute chorioamnionitis, and the morphological characteristics of blood-borne infection were mainly acute or chronic villitis, as well as villous interstitial inflammation. Identification of viral inclusions suggested viral etiology, while the final diagnosis was relied on laboratory testing. Among the 6 cases related to fetal abnormality, the diagnostic value of placenta was limited and the diagnosis could be made with fetal autopsy. Conclusion: The causes of perinatal fetal death are complex, diverse, and often the synergistic result of multiple factors. Fetal autopsy and placental pathology are the key technical means to identify the cause of death and deserve more attention and utilization.

Singleton placentas with abnormal shape: a clinicopathological analysis of 130 cases / 中华病理学杂志

Objective: To investigate the pathological characteristics of singleton placenta with abnormal shape and its influence on the outcome of maternal-fetal pregnancy. Methods: The clinicopathological data of singleton placentas with abnormal shape from January 2014 to December 2020 in the Department of Pathology, Haidian Maternal and Children Health Hospital were analyzed retrospectively. Results: There were 130 singleton placentas with abnormal shape in this cohort, including 48 succenturiate placentas, 12 bilobed placentas, 50 marginate placentas, 13 circumvallate placentas, 3 annular placentas, 2 membranous placentas and 2 fenestrated placentas. Gestational age ranged from 29+5 to 40+4 weeks. There were 51 cases of premature rupture of membranes, 11 cases of placenta previa, 5 cases of placental abruption, 15 cases of placental adhesion/implantation and 27 cases of postpartum hemorrhage. There were 46 preterm fetuses,28 fetuses with fetal growth restriction, 22 fetuses with intrauterine distress, and 1 fetus with intrauterine death. Grossly, the placental lobules of succenturiate placentas had apparent size difference, while two lobules of bilobate placenta were more consistent. The chorionic plate size was smaller than the bottom plate of circumvallate placenta, the folded fetal membrane in the rim of placenta was thickened (termed marginate placenta if there was no thickening). The membranous placenta was characterized by a thin, large membrane-like shape. Annular placenta showed characteristic hollow cylinder, ring or horseshoe-shape. Fenestrated placenta was characterized by tissue defects near central area. Microscopically, functional/morphologic changes were the main manifestations of inadequate maternal-fetal perfusion, including villous infarction, distal villous dysplasia and excessive villous maturation. Conclusions: The abnormal shaped singleton placentas showed variable extent of inadequate maternal-fetal perfusion, which may lead to adverse pregnancy outcomes such as premature delivery, fetal growth restriction, intrauterine distress or fetal death.

Genetic testing and analysis of 2 cases of trisomy 11 mosaicism / 南方医科大学学报

Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management.

Expression and role of anti-oxidative damage factors in the placenta of preterm infants with premature rupture of membranes / 中国当代儿科杂志

OBJECTIVES@#To study the association of the anti-oxidative damage factors nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO1) with preterm premature rupture of membranes (PPROM).@*METHODS@#A prospective study was conducted. The neonates who were hospitalized in Yanbian Hospital from 2019 to 2020 were enrolled as subjects, among whom there were 30 infants with PPROM, 32 infants with term premature rupture of membranes (TPROM), and 35 full-term infants without premature rupture of membranes (PROM). Hematoxylin and eosin staining was used to observe the inflammatory changes of placental tissue. Immunohistochemical staining was used to measure the expression of Nrf2, HO-1, and NQO1 in placental tissue. Western blot was used to measure the protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue.@*RESULTS@#Compared with the PPROM group, the TPROM group and the non-PROM full-term group had significantly higher positive expression rates and relative protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue (P<0.05). There were no significant differences in the positive expression rates and relative protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue between the TPROM and non-PROM full-term groups (P>0.05).@*CONCLUSIONS@#The low expression levels of Nrf2, HO-1, and NQO1 in placental tissue may be associated with PPROM, suggesting that anti-oxidative damage is one of the directions to prevent PPROM.

Comparison of biological characteristics of placenta mesenchymal stem cells derived from fetus / 生物工程学报

Mesenchymal stem cells (MSCs) have broad application potentials in regenerative medicine and translational medicine. Obtaining large quantities of primary-cultured MSCs and select the most suitable cell origin for targeted diseases are critical to research. To select the most suitable seed cells of MSCs from different origins for clinical treatment and research, biological characteristics of MSCs from human umbilical cord and placenta were compared. These include cell morphology, surface marker expression, differentiation and karyotype. Transcriptome sequencing of four MSCs from fetus were performed and the results were analyzed from the perspective of proliferation and cytokine secretion. The results revealed that MSCs from umbilical cord (UC), amniotic membrane (AM), chorionic membrane (CM), chorionic villi (CV) and deciduae (DC) met the minimum standards of the International Society of Cell Therapy (ISCT) in 2006 and had the general characteristics of stem cells. Karyotype analysis showed that MSCs derived from UC, AM, CM and CV were all from fetus except that the DC-MSCs were from mother. Transcriptome sequencing analysis showed that hMSCs from umbilical cord and placenta had similar gene expression patterns, while different expression patterns were observed in specific genes involved in cell cycle, cell division, cell death, cell growth and development. These genes play important roles in transcriptional regulation, DNA repair, DNA replication and chromosome stability, which were momentous components of cellular or subcellular fraction movement, cell communication, cell tissue protrusions, cytokine secretion and hormone metabolism. Transcriptome sequencing analysis explained the differences in biological characteristics among MSCs from different sources, while verification experiments based on the transcriptome sequencing results showed that the proliferation and cytokine secretion capabilities of MSCs from different sources were significantly different. In all, UC-MSCs and CV-MSCs with stronger proliferation and higher levels of paracrine factors secretion may show their respective advantages in treating diseases.

Advances on human amniotic epithelial cells and its clinical application potential / 生理学报

Human amniotic epithelial cells (hAECs) are epithelial cells located on the placental amnion near the fetus. Different from other placental-derived stem cells, hAECs are derived from embryonic epiblast, and have been considered as seed cells for regenerative medicine. hAECs possess embryonic stem cell-like multi-differentiation capabilities and adult stem cell-like immunomodulatory properties. Compared with other types of stem cells, special properties of hAECs make them unique, including easy isolation, abundant cell numbers, non-tumorigenicity after transplantation, and the obviation of ethical debates. During the past two decades, the therapeutic potential of hAECs has been extensively investigated in various diseases. Accumulating evidence has demonstrated that hAECs contribute to repairing and remodeling the function of damaged tissues and organs through different molecular mechanisms. This article provides an in-depth review of the biological characteristics of hAECs, summarizes the research status of hAECs, and discusses the clinical application prospects of hAEC-based cell therapy.

Comparative analysis of trophoblasts and angiogenesis in human placental compartments / Análisis comparativo de trofoblastos y angiogénesis en compartimentos placentarios humanos

SUMMARY: Trophoblasts perform different functions depending on their location. This study aimed to obtain structural clues about the functions of villous and extravillous trophoblasts by using light and electron microscopy. Term placenta samples were obtained from 10 healthy pregnant women following cesarean sections. Frozen sections were stained with hematoxylin-eosin, semi- thin sections were stained with toluidine blue and examined with a light microscope, while thin sections were contrasted using uranyl acetate-lead citrate and evaluated under an electron microscope. Fine structural features of villous trophoblasts overlapped some villous stromal cells. In addition to the usual appearance of mature capillaries in villous stroma, we demonstrated and reported maturational stages of angiogenetic sprouts in term placenta. Extravillous trophoblasts were classified according to their location: fibrinoid, chorion, trophoblastic, column, maternal vascular endothelium, or decidua. All of these trophoblasts shared some ultrastructural features but also were distinct from each other. In decidua, it was noted that the endothelial lining of some vessels was invaded by a few endovascular trophoblasts with irregular microvilli. These cells shared some ultrastructural properties with both villous trophoblasts and stromal cells. Examination showed that angiogenesis was still present in term placentas and that trophoblasts, endothelial and stromal cells have very similar properties ultrastructurally, suggesting they represent transformational forms.

RESUMEN: Los trofoblastos dependiendo de su ubicación realizan diferentes funciones. Este estudio tuvo como objetivo obtener pistas estructurales sobre las funciones de los trofoblastos vellosos y extravellosos mediante el uso de microscopía óptica y electrónica. Se obtuvieron muestras de placenta a término de 10 mujeres embarazadas sanas después de cesáreas. Las secciones congeladas se tiñeron con hematoxilina-eosina, las secciones semidelgadas se tiñeron con azul de toluidina y se examinaron con un microscopio óptico, mientras que las secciones delgadas se contrastaron con acetato de uranilo-citrato de plomo y se evaluaron con un microscopio electrónico. Las finas características estructurales de los trofoblastos vellosos se superponen a algunas células estromales vellosas. Además de la apariencia habitual de capilares maduros en el estroma velloso, demostramos e informamos etapas de maduración de brotes angiogenéticos en la placenta a término. Los trofoblastos extravellosos se clasificaron según su localización: fibrinoide, corion, trofoblástico, columna, endotelio vascular materno o decidua. Todos estos trofoblastos compartían algunas características ultraestructurales, pero también eran distintos entre sí. En decidua se observó que el revestimiento endotelial de algunos vasos estaba invadido por unos pocos trofoblastos endovasculares con microvellosidades irregulares. Estas células compartían algunas propiedades ultraestructurales tanto con los trofoblastos vellosos como con las células del estroma. El examen mostró que la angiogénesis todavía estaba presente en las placentas a término y que los trofoblastos, las células endoteliales y estromales tienen propiedades ultraestructurales muy similares, lo que sugiere que representan formas de transformación.

Equine abortion associated with placentitis caused by Pasteurella pneumotropica / Aborto equino associado a placentite por Pasteurella pneumotropica

Pasteurella pneumotropica is a bacterium that has so far not been described as a cause of placentitis in animals. Two cases of aborted equine fetuses were sent to the Department of Veterinary Pathology of the "Universidade Federal do Rio Grande do Sul" (SPV-UFRGS) for anatomopathological examination. Both cases presented suppurative placentitis associated with multiple basophilic bacterial cells. After bacterial isolation and biochemical analysis, P. pneumotropica was identified.(AU)

Pasteurella pneumotropica é uma bactéria que até o momento não foi descrita como causa de placentite em animais. Dois casos de fetos equinos abortados foram enviados ao Setor de Patologia Veterinária da Universidade Federal do Rio Grande do Sul (SPV-UFRGS) para exame anatomopatológico. Em ambos os casos se observou placentite supurativa associada a múltiplas colônias bacterianas basofílicas. Após o isolamento bacteriano e análise bioquímica, indentificou-se P. pneumotropica.(AU)

Investigation of FAS and IL-6 expression in placentas with HELLP syndrome / Investigación de la expresión de FAS e IL-6 en placentas con síndrome de HELLP

SUMMARY: The aim of our study was to investigate the effect of inflammation in the placenta on the pro-apoptotic development after severe preeclampsia. Placenta tissue samples of 15 HELLP syndrome and 15 healthy 35-38th week-pregnant women were involved in the study. Tissue samples were taken only from the maternal side of the placenta and fixed in 10 % formaldehyde, then blocked in paraffin wax and 4-6 mm-thick sections were cut and stained with Harris Hematoxylene-Eosin. Antigen retrieval was performed for sections, incubated with FAS antibody and anti-IL-6 antibody. After the application of streptavidin peroxidase followed by AEC chromogen solution, sections were counterstained with Harris hematoxylin. Significant thickening of the fibrinoid layer, degeneration and apoptotic change in decidua cells, marked increase in the hyalinized area, degenerative changes in the syncytial regions of the chorionic villus and an increase in syncytial nodes and bridges and IL- expression were observed as positive. FAS expression was positive in the pycnotic nuclei of decidual cells in the maternal region and in the syncytial regions. It was observed that the proapoptotic process increased as a result of severe preeclampsia. It was concluded that the control of cytokine activity and reduction of pro-apoptotic signal during the inflammation process will slow down the development of HELLP syndrome.

RESUMEN: El objetivo de nuestro estudio fue investigar el efecto de la inflamación en la placenta sobre el desarrollo proapoptótico después de la preeclampsia severa. Se recogieron muestras de tejido de placenta de 15 mujeres con síndrome de HELLP y 15 mujeres sanas con un embarazo de 35 a 38 semanas. Se tomaron muestras de tejido solo del lado materno de la placenta y se fijaron en formaldehído al 10 %, luego se bloquearon en parafina y se cortaron secciones de 4-6 mm de espesor y se tiñeron con hematoxilena-eosina de Harris. La recuperación del antígeno se realizó para secciones, incubadas con anticuerpo FAS y anticuerpo anti-IL-6. Después de la aplicación de estreptavidina peroxidasa seguida de solución de cromógeno AEC, las secciones se contrastaron con hematoxilina de Harris. Se observó como positivo un engrosamiento significativo de la capa fibrinoide, degeneración y cambio apoptótico en las células de la decidua, aumento marcado en el área hialinizada, cambios degenerativos en las regiones sincitiales de la vellosidad coriónica y un aumento en los nódulos y puentes sincitiales y la expresión de IL-6. La expresión de FAS fue positiva en los núcleos picnóticos de las células deciduales en la región materna y en las regiones sincitiales. Se observó que el proceso proapoptótico se incrementó como consecuencia de la preeclampsia severa. Se concluyó que el control de la actividad de las citocinas y la reducción de la señal proapoptótica durante el proceso de inflamación ralentizarán el desarrollo del síndrome de HELLP.

Participação dos neutrófilos durante a implantação embrionária no desenvolvimento da placenta em camundongos / Participation of neutrophils during embryonic implantation in the placental development in mice

A implantação do embrião na parede uterina é um processo complexo que consiste na interação do blastocisto com as células epiteliais do útero, e depende de diferentes tipos celulares do microambiente uterino. Embora a literatura mostre a participação de neutrófilos neste processo, os dados ainda são incipientes para proposição da função exata destas células nos períodos iniciais da gestação. Dados do nosso grupo de pesquisa mostraram que neutrófilos pró-angiogênicos induzem a tolerância gestacional, e que a depleção de neutrófilos durante as fases iniciais da gestação prejudica a implantação do blastocisto e a progressão da gestação. Com base nestes resultados, o presente estudo visou investigar se a depleção de neutrófilos na fase pré-receptiva da janela de implantação do blastocisto altera a morfologia placentária. Para tanto, foi utilizado o modelo de gestação alogênica, onde camundongos fêmeas C57BL/6, após cruzamento com machos Balb/C foram tratadas com anticorpo anti-Ly6G ou isotipo no dia 1,5 da gestação (24 horas após a detecção do plug vaginal) em dose suficiente para manter a depleção de neutrófilos circulantes por 48 horas (200µg/ 500µL; i.p). No final da gestação (dia 18,5), o sangue periférico foi coletado e, em seguida, os animais foram submetidos a laparotomia para retirada da placenta, a qual foi submetida à análise histológica. As análises dos leucócitos circulantes evidenciaram a efetividade do tratamento para depleção de neutrófilos periféricos. A análise histológica mostrou alterações significativas na morfologia da placenta nos animais tratados com anti-Ly6G. Foram detectadas a redução da zona juncional, de células trofoblásticas e de fatores angiogênicos, como fator de crescimento do endotélio vascular (VEGF), e das moléculas de adesão intracelular-1 (ICAM-1) e de plaqueta e endotélio (PECAM-1). Esses dados evidenciam a importância dos neutrófilos nos primeiros dias de gestação para o desenvolvimento da placenta

Blastocyst implantation is a complex process, consisting of the interaction between blastocyst and uterine epithelial cells. Also, it is well known that the implantation site resembles an inflammatory response, with a profusion of recruited immune cells into the endometrial stroma and lumen from the blood. The role of macrophages, natural killers, and dendritic cells have been extensively studied, however, the participation of neutrophils in this process remains unclear. Data from our research group showed that pro-angiogenic neutrophils induced gestation tolerance, also peripheral neutrophils depletion at the time of active placental development led to smaller embryo sizes and abnormal placentation in mice. In this context, the present study aimed to investigate whether pharmacological depletion of neutrophils in mice in the blastocyst implantation phase alters placental morphology. Therefore, C7/BL/6 female mice, after mating with Balb/C males, were treated with an anti-Ly6G antibody or isotype on day 1 of gestation (after detection of the vaginal plug) at a dose sufficient to maintain the depletion of circulating neutrophils for 48 hours (200 µg/500µL; i.p). At the end of the gestational day (day 18), peripheral blood was collected, and then the animals were submitted to laparotomy for the placenta removal and subsequent histological analysis. The analysis of circulating leukocytes from neutrophils depleted mice showed a reduction of peripheral neutrophils up to 48 hours after antibody injection. The histological analysis showed significant alterations in the placenta morphology of the animals treated with anti-Ly6G. The morphometric analyses showed a reduction in the size of neutrophils depleted placenta due to diminished junctional zone and reduction of trophoblast cells. Also, it was observed a reduction of vascular endothelial growth factors (VEGF), reduction of adhesion molecules intracell-1 (ICAM-1), and platelets and endothelium (PECAM-1) positive cells in the junctional zone. In conclusion, these data show the importance of neutrophils on the first days of pregnancy for the development of the placenta

Dyspnea and COVID-19: A Review of Confounding Diagnoses during the Postpartum Period / Dispneia e COVID-19: uma revisão de diagnósticos confundidores no período pós-parto

Abstract The puerperium is a complex period that begins with placental delivery and lasts for 6 weeks, during which readaptation of the female organism and redistribution of blood volume occur. This period is conducive to the occurrence of thromboembolic events. In the context of the SARS-CoV-2 pandemic, the virus responsible for COVID-19, the attention of the scientific community and health professionals has been focused on obtaining insights on different aspects of this disease, including etiology, transmission, diagnosis, and treatment. Regarding the pregnancy-postpartum cycle, it is opportune to review the clinical conditions that can occur during this period and to investigate dyspnea as a postpartum symptom in order to avoid its immediate association with COVID-19 without further investigation, which can lead to overlooking the diagnosis of other important and occasionally fatal conditions.

Resumo O puerpério é um período complexo que se inicia com a dequitação placentária e dura por 6 semanas, no qual a readaptação do organismo materno e a redistribuição do volume sanguíneo ocorrem, além de ser também um cenário propício para eventos pró-trombóticos. No contexto da pandemia de SARS-CoV-2, vírus responsável pela COVID-19, a atenção da comunidade científica e dos profissionais da saúde está voltada a elucidar os aspectos da doença, como a etiologia, a transmissão, o diagnóstico e o tratamento. Considerando o ciclo gravídico-puerperal, é oportuna a revisão de condições clínicas que ocorrem durante este período e que apresentam a dispneia como sintoma, a fimde evitar que ela seja automaticamente associada à COVID-19 sem investigações aprofundadas, o que pode levar à negligência do diagnóstico de outras condições importantes e que podem ser, por vezes, fatais.

Determination of the relationship among cell proliferation, metabolic activity and stage of pregnancy by AgNORs as markers in bovine placenta / Determinación de la relación entre la proliferación celular, la actividad metabólica y la etapa de preñez por los AgNOR como marcadores en la placenta bovina

SUMMARY: Nucleolus Organizer Regions (NORs) are defined as nucleolar components containing argyrophilic proteins selectively stained by silver methods (AgNORs). Several investigations have shown the AgNOR quantity and area represent a valuable parameter of cell kinetics, since they reflect the level of activity and cellular proliferation. This article addresses an evaluation of the functional activity and relation between days of pregnancy and proliferative capacity of trophoblastic mononucleate and binucleate cells from bovine placentomes. Both the number and size of AgNORs were determined in different phases of gestation by silver nitrate staining in conventional histological slides. The results showed a significant increase (from 1 to 12 AgNORs) in the number of AgNORS per trophoblastic mononucleate cell in the 3rd trimester, with predominance of 4-6 AgNORs/cell. In the 1st and 2nd trimesters, the number ranged between 1 and 9 AgNORs/cell, with predominance of 1-3 AgNORs. No significant differences were observed between the 2nd and 3rd trimesters, but in the first, in binucleate cells (19-27 and 10-18 AgNORs/cell, respectively) - this number was higher than the one registered in trophoblastic mononucleate cells in the same period. Thus, AgNORs can be used as markers of the proliferative placental cell cycle and established a relation between number of AgNORs and days of gestation. This relation can be used for diagnoses and prognoses of several placental pathologies, including pregnancy losses from manipulated embryos.

RESUMEN: Las Regiones Organizadoras de Nucléolos (NOR) se definen como componentes nucleolares que contienen proteínas argirofílicas teñidas selectivamente por métodos de plata (AgNOR). Varias investigaciones han demostrado que la cantidad y el área de AgNOR representan un parámetro importante de la cinética celular, ya que reflejan el nivel de actividad y proliferación celular. Este trabajo analiza la actividad funcional y la relación entre los días de preñez y la capacidad proliferativa de las células trofoblásticas mononucleadas y binucleadas de placentomas bovinos. Tanto el número como el tamaño de los AgNOR se determinaron en diferentes fases de la gestación mediante tinción con nitrato de plata en portaobjetos histológicos convencionales. Los resultados mostraron un aumento significativo (de 1 a 12 AgNOR) en el número de AgNORS por célula mononucleada trofoblástica en el tercer trimestre, con predominio de 4-6 AgNOR / célula. En el primer y segundo trimestre, el número osciló entre 1 y 9 AgNOR / célula, con predominio de 1-3 AgNOR. No se observaron diferencias significativas entre el 2do y 3er trimester; en el primer trimestre, en células binucleadas (19-27 y 10-18 AgNORs / célula, respectivamente) - este número fue superior a la cantidad registrada en células mononucleadas trofoblásticas en el mismo período. Por tanto, los AgNOR se pueden utilizar como marcadores del ciclo celular placentario proliferativo y se establece una relación entre el número de AgNOR y los días de gestación. Esta relación puede ser útil en el diagnóstico y pronóstico de varias patologías placentarias, incluidas las pérdidas de preñeces de embriones manipulados.

Secuencia de perfusión arterial reversa en embarazo gemelar; coagulación de arteria nutricia. Reporte del primer caso en el país / Twin reversed arterial perfusion sequence; coagulation of the umbilical cord. A report on the first case in Uruguay / Seqüência reversa de perfusão arterial na gravidez gemelar; coagulação da artéria nutritiva. Relato do primeiro caso no país

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.

SARS-CoV-2 (COVID-19) en gestación y placenta: una revisión narrativa sobre el estado del arte / SARS-CoV-2 (COVID-19) in pregnancy and placenta: a narrative review on state of the art

Resumen La crisis sanitaria por la pandemia de COVID-19, enfermedad generada por la infección con el SARS-CoV-2, ha llevado a la pérdida de más de 25,000 vidas en Chile, con más de 370,000 mujeres entre 15 y 44 años con infección confirmada. Se ha reportado una mayor vulnerabilidad de las mujeres gestantes en cuanto a desarrollar cuadros de COVID-19 graves o críticos, con un aumento de la incidencia de resultados obstétricos y perinatales adversos. Es relevante considerar que un alto porcentaje de las gestantes infectadas con SARS-CoV-2 son asintomáticas, lo cual nos pone en alerta en cuanto a que ciertos efectos del virus durante la gestación podrían no ser evidentes para la observación clínica. Se ha demostrado la presencia de SARS-CoV-2 en la placenta, asociándose la infección placentaria con alteraciones vasculares que podrían afectar el flujo útero-placentario. Por otro lado, la transmisión vertical al feto parece que es poco frecuente, pero factible. Se resumen las evidencias disponibles hasta el momento sobre los principales efectos de la COVID-19 en la gestación, con énfasis en los estudios sobre los efectos de la infección por SARS-CoV-2 en la placenta. El objetivo es relevar el tema, destacando que son diversas las preguntas que necesitan ser abordadas, considerando el impacto que esta pandemia podría tener sobre la salud gestacional.

Abstract In Chile, the COVID-19 pandemic, a disease induced by infection with SARS-CoV-2, has caused more than 25,000 deaths. More than 370,000 women between 15 and 44 years have been detected with the infection. The greater vulnerability of pregnant women has been reported, mainly related to a higher risk for severe or critical COVID-19, with an increased incidence of adverse obstetrics and perinatal outcomes. It is relevant to consider that a high percentage of pregnant women infected with SARS-CoV-2 are asymptomatic for COVID-19, which indicates that specific effects of the virus during pregnancy may not be evident from clinical observation. The presence of SARS-CoV-2 in the placenta has been demonstrated, associating placental infection with vascular alterations that could affect utero-placental flow. On the other hand, vertical transmission to the fetus is rare but feasible. This manuscript summarizes the evidence available to date on the main effects of COVID-19 in pregnancy, emphasizing studies about the impact of SARS-CoV-2 in the placenta. This review aims to promote this issue, highlighting that several questions need to be addressed, considering the effect this pandemic could have on gestational health.

Placental Findings in Preterm and Term Preeclampsia: An Integrative Review of the Literature / Achados placentários na pré-eclâmpsia pré-termo e a termo: Uma revisão integrativa da literatura

Abstract Introduction Preeclampsia (PE) is a pregnancy complication associated with increased maternal and perinatal morbidity and mortality. The disease presents with recent onset hypertension (after 20 weeks of gestation) and proteinuria, and can progress to multiple organ dysfunction, with worse outcomes among early onset preeclampsia (EOP) cases (<34 weeks). The placenta is considered the root cause of PE; it represents the interface between the mother and the fetus, and acts as a macromembrane between the two circulations, due to its villous and vascular structures. Therefore, in pathological conditions, macroscopic and microscopic evaluation can provide clinically useful information that can confirm diagnosis and enlighten about outcomes and future therapeutic benefit. Objective To perform an integrative review of the literature on pathological placental findings associated to preeclampsia (comparing EOP and late onset preeclampsia [LOP]) and its impacts on clinical manifestations. Results: Cases of EOP presented worse maternal and perinatal outcomes, and pathophysiological and anatomopathological findings were different between EOP and LOP placentas, with less placental perfusion, greater placental pathological changes with less villous volume (villous hypoplasia), greater amount of trophoblastic debris, syncytial nodules, microcalcification, villous infarcts, decidual arteriolopathy in EOP placentas when compared with LOP placentas. Clinically, the use of low doses of aspirin has been shown to be effective in preventing PE, as well asmagnesium sulfate in preventing seizures in cases of severe features. Conclusion The anatomopathological characteristics between EOP and LOP are significantly different, with large morphological changes in cases of EOP, such as

Resumo Introdução A pré-eclâmpsia (PE) é uma complicação da gravidez associada ao aumento da morbidade e mortalidade materna e perinatal. A doença se apresenta com hipertensão de início recente (após 20 semanas de gestação) e proteinúria, que pode progredir para disfunção de múltiplos órgãos, com resultados piores entre os casos de início precoce (<34 semanas). A placenta é considerada a principal causa da PE, representando a interface entre a mãe e o feto, e atuando como uma macromembrana entre as duas circulações, devido às suas estruturas vilosas e vasculares, demodo que, em condições patológicas, avaliações macroscópicas e microscópicas podem fornecer informações clinicamente úteis, que podem fornecer diagnóstico, prognóstico e benefício terapêutico. Objetivo Realizar uma revisão integrativa da literatura para compreender e descrever os achados placentários patológicos associados à pré-eclâmpsia e seus impactos nas manifestações clínicas. Resultados Os casos de início precoce apresentaram piores desfechos maternos e perinatais, e os achados fisiopatológicos e anatomopatológicos foram diferentes entre as placentas de início precoce e início tardio, commenor perfusão placentária, maiores alterações patológicas placentárias commenor volume viloso (hipoplasia vilosa), maior quantidade de debris trofoblásticos, nódulos sinciciais, microcalcificação, infartos vilosos, arteriolopatia decidual em placentas de início precoce quando comparadas com placentas de início tardio. Clinicamente, o uso de baixas doses de aspirina tem se mostrado significativo na prevenção da PE, assim como o sulfato de magnésio na prevenção de convulsões na doença com manifestações de gravidade. Conclusão As características anatomopatológicas entre a pré-eclâmpsia precoce e tardia são significativamente diferentes, com grandes alterações morfológicas nos casos de início precoce, como hipóxia, infartos vilosos e hipoplasia, entre outros, na tentativa de estabilizar o fluxo sanguíneo para o feto. Portanto, um entendimento comum do exame macroscópico básico e dos padrões histológicos da lesão é importante para maximizar o benefício diagnóstico, prognóstico e terapêutico do exame da placenta e, consequentemente, reduzir os riscos para a mãe e o feto.

Prenatal Ultrasound Diagnosis of Biometric changes in the Brain of Growth Restricted Fetuses. A Systematic Review of Literature / Diagnóstico ecográfico de alterações biométricas no cérebro de fetos comrestrição do crescimento fetal. Uma revisão sistemática da literatura

Abstract Fetal growth restriction (FGR) occurswhen the fetus does not reach its intrauterine potential for growth and development as a result of compromise in placental function. It is a condition that affects 5 to 10% of pregnancies and is the second most common cause of perinatal morbidity and mortality. Children born with FGR are at risk of impaired neurological and cognitive development and cardiovascular or endocrine diseases in adulthood. The purpose of the present revision is to perform a literature search for evidence on the detection and assessment by ultrasound of brain injury linked to FGR during fetal life. Using a systematic approach and quantitative evaluation as study methodology, we reviewed ultrasound studies of the fetal brain structure of growth-restricted fetuses with objective quality measures. A total of eight studies were identified. High quality studies were identified for measurement of brain volumes; corpus callosum; brain fissure depth measurements, and cavum septi pellucidi width measurement. A low-quality study was available for transverse cerebellar diameter measurement in FGR. Further prospective randomized studies are needed to understand the changes that occur in the brain of fetuseswith restricted growth, as well as their correlation with the changes in cognitive development observed.

Resumo A restrição do crescimento fetal (RCF) ocorre quando umfeto não consegue atingir seu potencial de crescimento intrauterino, na maioria das vezes por compromisso da função placentária. É uma condição que afeta de 5 a 10% das gravidezes e é a segunda causa mais comum de morbidade e mortalidade perinatal. Crianças nascidas com RCF incorrem em maior risco de atraso no desenvolvimento neurológico e cognitivo, bem como de doenças cardiovasculares e/ou endócrinas, na idade adulta. O objetivo desta revisão foi o de pesquisar na literatura evidência sobre o diagnóstico pré-natal por ecografia de lesões cerebrais relacionadas com a RCF. Utilizando uma abordagem sistemática, avaliamos de forma quantitativa a metodologia dos oito estudos que preencheram os critérios de inclusão e foram, assim, incluídos nesta revisão. Foram identificados estudos de alta qualidade para a medição dos volumes cerebrais;medição do corpo caloso; medição da profundidade das incisuras cerebrais emedição do cavum do septo pelúcido. Os autores identificaram um estudo de qualidade inferior sobre a medição transversal do diâmetro transcerebelar em fetos com RCF. Mais estudos prospectivos randomizados são necessários para perceber quais as alterações que ocorrem no cerébro dos fetos com restrição do seu crescimento, bem como, a sua correlação com as alterações do desenvolvimento cognitivo observadas.

Muerte fetal por infección bacteriana ascendente: método diagnóstico, una revisión narrativa. ¿Por qué el método que incluye estudio placentario, evaluación de datos clínicos y de laboratorio es eficiente en identificar la infección bacteriana ascendente como causa de muerte fetal? / Fetal death from ascending bacterial infection: diagnostic method, a narrative review. Why is the method that includes placental study, evaluation of clinical and laboratory data efficient in identifying ascending bacterial infection as the cause of fetal death?

Resumen Esta revisión narrativa incluye estudios publicados sobre métodos de clasificación de mortinatos y su eficiencia para identificar la infección bacteriana ascendente (IBA) como causa de muerte fetal (MF), mediante búsqueda en PubMed, Cochrane, Embase, ScienceDirect, Wiley Online Library, Scielo. Muchos niños mueren antes de nacer en todo el mundo y no se ha logrado reducir la MF porque los métodos empleados no han sido los adecuados y porque no se diagnostica la IBA, la causa más frecuente de MF en un hospital público de Chile. Los sistemas que utilizan los datos clínicos, de laboratorio y estudio placentarios, INCODE, CORM, son los más eficientes para identificar la IBA como origen de la MF. Se ha demostrado que los marcadores específicos de infección/inflamación placentaria, corioamnionitis histológica/funisitis aguda son de mayor eficiencia para diagnosticar la IBA que la autopsia fetal, que el cultivo de líquido amniótico es más eficiente que el cultivo de la placenta para detectar invasión microbiana de la cavidad amniótica y que la muestra de sangre de cordón es eficiente para el diagnóstico etiológico de la infección. El conocimiento de la IBA como causa inicial de MF, ayuda a elaborar guías y normas de prevención de la MF por esta condición.

Abstract This narrative review includes published studies of stillbirth classification methods and their efficiency in identifying ascending bacterial infection (ABI), as a cause of fetal death (FD), by searching PubMed, Cochrane, Embase, ScienceDirect, Wiley Online Library, Scielo. Many children die before birth around the world and it has not been possible to reduce FD because the methods used have not been adequate and because ABI, the most frequent cause of FD in a public hospital in Chile, is not diagnosed. Systems using clinical, laboratory and placental study data, INCODE, CORM, are more efficient in identifying ABI as the origin of FD. Specific markers of infection/placental inflammation, histologic chorioamnionitis/acute funitis have been shown to be more efficient in diagnosing ABI than fetal autopsy, that amniotic fluid culture is more efficient than placental culture for detect microbial invasion of the amniotic cavity and that the cord blood sample is efficient for the etiological diagnosis of the infection. The knowledge of the ABI as the initial cause of FD helps to develop guidelines and norms for preventing FD due to this condition.