Endometrial mesenchymal stromal/stem cells improve regeneration of injured endometrium in mice

BACKGROUND: The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. METHODS: Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. RESULTS: Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. CONCLUSIONS: Our findings suggest eMSC improves regeneration of injured endometrium in mice.

Morfometría en placentas procedentes de embarazos gemelares / Morphometry in placentas from twin pregnancies

Introducción: La disfunción de la placenta puede originar complicaciones fetales, restricción del crecimiento intrauterino y complicaciones maternas, como la preeclampsia. Objetivo: Identificar el patrón morfométrico de las placentas gemelares y su relación con la corionicidad, el peso del recién nacido y las malformaciones plancentarias. Método: Se realizó un estudio descriptivo en una muestra de 16 gestantes con embarazo gemelar, 25 placentas y los 32 recién nacidos. Se estudiaron las variables malformaciones placentarias, tipo de placenta, presencia de calcificaciones, peso del recién nacido, peso de la placenta, volumen placentario, diámetro placentario y espesor placentario; se determinó la asociación del peso del recién nacido, con el tipo de placenta y la presencia de calcificaciones, las malformaciones placentarias, así como espesor, diámetro, volumen y peso, con el tipo de placenta. Resultados: Hubo mayor frecuencia de recién nacidos de placentas monocoriónicas (60 por ciento) sin que la asociación fuera estadísticamente significativa; las malformaciones placentarias se relacionaron de forma significativa con el tipo de placenta, así como el peso del recién nacido y la presencia de calcificaciones placentarias, y el espesor, diámetro, volumen y peso de la placenta, con el tipo de plancenta (p< 0,01). Conclusiones: Son más frecuentes las placentas dicoriónicas y estas tienen menos malformaciones; existe relación entre el bajo peso del recién nacido y la presencia de calcificaciones placentarias, así como entre el espesor, diámetro, volumen y peso de la placenta, con el tipo de placenta(AU)

Introduction: Placental dysfunction can originate fetal complications, intrauterine growth restriction and maternal complications, such as preeclampsia. Objective: To identify the morphometric pattern of twin placentas and its relationship with chorionicity, newborn weight and placental malformations. Methods: A descriptive study was carried out in a sample of 16 pregnant women with twin pregnancy, 25 placentas and 32 newborns. The variables placental malformations, type of placenta, presence of calcifications, newborn weight, placental weight, placental volume, placental diameter and placental thickness were studied; the association of newborn weight with the type of placenta and the presence of calcifications, placental malformations, as well as thickness, diameter, volume and weight, with the type of placenta was determined. Results: There was a higher frequency of newborns with monochorionic placentas (60 percent) without the association being statistically significant; placental malformations were significantly related to placenta type, as well as newborn weight and the presence of placental calcifications, and placental thickness, diameter, volume and weight, with placenta type (p< 0.01). Conclusions: Dichorionic placentas are more frequent and these have fewer malformations; there is a relationship between low newborn weight and the presence of placental calcifications, as well as between placental thickness, diameter, volume and weight, with the type of placenta(AU)

Corioamnionitis Histológica Asociada a Muerte Fetal / Histological Chorioamnionitis Associated with Fetal Death

INTRODUCCIÓN. Anualmente ocurren más de 2 millones de muertes fetales a nivel mundial, siendo fundamental el estudio anatomopatológico placentario para disminuir el número de muertes inexplicadas. OBJETIVO. Revisar la literatura existente acerca de corioamnionitis histológica, los criterios para establecer su diagnóstico, su presencia y posible asociación en estudios de causas de muerte fetal. METODOLOGÍA. Se realizaron búsquedas en bases de datos electrónicas para recopilar estudios de causas de muerte fetal que incluyeron corioamnionitis histológica. RESULTADOS. Se encontraron 13 estudios que evaluaron mortalidad fetal y que entre sus causas incluyeron corioamnionitis histológica. DESARROLLO. El estudio microscópico placentario en muertes fetales es esencial al investigar una muerte fetal. Las anomalías placentarias son la causa más común de muerte fetal, la corioamnionitis aguda es la lesión inflamatoria más frecuente. Se detallaron los criterios más relevantes para definir corioamnionitis aguda histológica pero aún no se establece un consenso. Estudios de causas de muerte fetal en años recientes han reportado corioamnionitis histológica entre 6,3% y 41,3% de casos. Las alteraciones inflamatorias del líquido amniótico son una causa importante de muerte fetal, siendo la corioamnionitis la más frecuente en este grupo. CONCLUSIÓN. En estudios para determinar las causas de muerte fetal se evidenció corioamnionitis aguda histológica en hasta el 41,3% de casos, por lo que podría estar asociada a dicho evento. Sin embargo, es necesario establecer un sistema de estadiaje de corioamnionitis histológica mediante un panel de expertos a nivel mundial.

INTRODUCTION. Annually more than 2 million fetal deaths occur worldwide, being fundamental the placental anatomopathological study to reduce the number of unexplained deaths. OBJECTIVE. To review the existing literature on histological chorioamnionitis, the criteria to establish its diagnosis, its presence and possible association in studies of causes of fetal death. METHODOLOGY. Electronic databases were searched to collect studies of causes of fetal death that included histologic chorioamnionitis. RESULTS. Thirteen studies were found that evaluated fetal mortality and that included histologic chorioamnionitis among their causes. DEVELOPMENT: Placental microscopic study in fetal deaths is essential when investigating a fetal death. Placental abnormalities are the most common cause of fetal death, acute chorioamnionitis being the most frequent inflammatory lesion. The most relevant criteria for defining histologic acute chorioamnionitis have been detailed but consensus has not yet been established. Studies of causes of fetal death in recent years have reported histologic chorioamnionitis in between 6,3% and 41,3% of cases. Inflammatory changes in the amniotic fluid are an important cause of fetal death, with chorioamnionitis being the most frequent in this group. CONCLUSIONS. In studies to determine the causes of fetal death, histological acute chorioamnionitis was evidenced in up to 41,3% of cases, so it could be associated with this event. However, it is necessary to establish a histological chorioamnionitis staging system by means of a worldwide panel of experts.

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)

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.

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.

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 Infection and Placental Pathology Infecção por SARS-CoV-2 e patologia placentária

Abstract Placental pathophysiology in SARS-CoV-2 infection can help researchers understand more about the infection and its impact on thematernal/neonatal outcomes. This brief review provides an overview about some aspects of the placental pathology in SARSCoV- 2 infection. In total, 11 papers were included. The current literature suggests that there are no specific histopathological characteristics in the placenta related to SARSCoV- 2 infection, but placentas frominfected women aremore likely to show findings of maternal and/or fetal malperfusion. The most common findings in placentas from infected women were fibrin deposition and intense recruitment of inflammatory infiltrates. The transplacental transmission of this virus is unlikely to occur, probably due to low expression of the receptor for SARS-CoV-2 in placental cell types. Further studies are needed to improve our knowledge about the interaction between the virus and the mother-fetus dyad and the impact on maternal and neonatal/fetal outcomes.

Resumo A fisiopatologia da placenta na infecção por SARS-CoV-2 pode ajudar os pesquisadores a entender mais sobre a infecção e seu impacto nos resultados maternos/neonatais. Esta revisão breve fornece uma visão geral sobre alguns aspectos da patologia placentária na infecção por SARS-CoV-2. Ao todo, 11 artigos foram incluídos. A literatura atual sugere que não há características histopatológicas específicas nas placentas relacionadas à infecção por SARS-CoV-2, mas as placentas de mulheres infectadas têm maior probabilidade de apresentar achados de má perfusão materna e/ou fetal. Os achados mais comuns em placentas de mulheres infectadas foram deposição de fibrina e intenso recrutamento de infiltrado inflamatório. A transmissão transplacentária deste vírus é improvável, devido à baixa expressão do receptor para SARS-CoV-2 em tipos de células da placenta. Mais estudos são necessários para melhorar nosso conhecimento sobre a interação entre o vírus e a díade mãe-feto e o impacto nos resultados maternos e neonatais/fetais.

Malaria placentaria submicroscópica: histopatología y expresión de mediadores de procesos fisiológicos / Submicroscopic placental malaria: histopathology and expression of physiological process mediators

RESUMEN Objetivos: Relacionar entre sí los eventos histopatológicos de malaria placentaria (MP), el comportamiento de células inmunitarias y la expresión de genes asociados a citoquinas, hipoxia, inflamación y angiogénesis en placentas con o sin infección plasmodial. Materiales y métodos: Diseño transversal, con tres grupos independientes. Las mujeres y sus placentas fueron captadas en 2009-2016, en los hospitales de Puerto Libertador y Tierralta, noroccidente de Colombia. El tamaño muestral se definió por conveniencia. El diagnóstico malárico se basó en PCR cuantitativa en tiempo real. Resultados: Se estudiaron 20 casos con MP por P. vivax (MP-V), 20 casos de MP por P. falciparum (MP-F) y 19 sin MP; 95% de los casos de MP son infección plasmodial placentaria submicroscópica (IPPS). Los tres grupos difieren en frecuencia y cantidad de eventos histopatológicos. Los mediadores de procesos fisiológicos presentaron diferencia significativa entre grupos, excepto IL-2, VEGF, VEGFR-1 y C5a. Conclusiones: Las placentas con infección difieren claramente de las no infectadas. P. vivax se comporta tan patógeno como P. falciparum. Se resalta la aproximación al abordaje integral del problema de MP. La infección plasmodial placentaria submicroscópica causa alteraciones tisulares y en mediadores fisiológicos como lo hace la infección microscópica, aunque probablemente en menor grado.

ABSTRACT Objetives: To relate histopathological events of placental malaria (PM), immune cell behavior and gene expression associated with cytokines, hypoxia, inflammation and angiogenesis in placentas with or without plasmodial infection. Materials and methods: Transversal design, with three independent groups. Women were recruited, and their placentas were collected in 2009-2016, in the hospitals of Puerto Libertador and Tierralta, northwestern Colombia. The sample size was defined by convenience. The malaria diagnosis was based on real-time quantitative PCR. Results: We studied 20 cases of PM by P. vivax (PM-V), 20 cases of PM by P. falciparum (PM-F) and 19 without PM; 95% of the cases of PM are submicroscopic placental plasmodial infection (SPPI). The three groups differ in frequency and number of histopathological events. Physiological process mediators showed significant difference between groups, except IL-2, VEGF, VEGFR-1 and C5a. Conclusions: Infected placentas are clearly different from uninfected ones. P. vivax behaves as pathogenic as P. falciparum. The approximation to the integral approach of the problem of PM is underlined. Submicroscopic placental plasmodial infection causes tissue and physiological mediator alterations as does microscopic infection, although probably to a lesser degree.

Relationship between inflammatory markers, glycated hemoglobin and placental weight on fetal outcomes in women with gestational diabetes

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

Histopatologia placentária na infecção vertical por Zika Vírus e o comprometimento clínico no primeiro ano de vida / Placental histopathology in vertical Zika virus infection and clinical involvement in the first year of life

INTRODUÇÃO: Desde sua entrada no Brasil, o Zika vírus (ZIKV) foi relacionado a uma gama de alterações clínicas em fetos de gestantes infectadas. Além das alterações neurológicas, foram descritas as osteoarticulares, auditivas e oculares, constituindo atualmente o amplo espectro da Síndrome da Zika Congênita. O motivo pelo qual alguns lactentes nascem gravemente acometidos enquanto outros se apresentam assintomáticos ainda está sob investigação. Por ser uma infecção congênita, a análise da placenta pode contribuir para responder a esta questão. OBJETIVO: Estudar a histopatologia placentária na infecção vertical pelo ZIKV e sua relação com as alterações clínicas no primeiro ano de vida. METODOLOGIA: Estudo prospectivo de 60 binômios mãe-bebê com infecção por ZIKV comprovada na gestação ou período perinatal por RT-qPCR, cujos partos foram realizados em um hospital terciário no Rio de Janeiro, Brasil, em que a análise histopatológica da placenta e o acompanhamento clínico dos bebês até 12 meses de vida ocorreram no mesmo hospital. RESULTADOS: ZIKV foi mais diagnosticado no primeiro trimestre de gestação (48%). Quase 80% das 60 placentas analisadas apresentaram células inflamatórias: vilosite grau 1 foi o achado mais frequentemente encontrado (55%), seguido de vilosite grau 2 (15%) e vilosite de alto grau (8%). Em 22% não identificamos vilosite. O retardo da maturação vilosa (graus 2 e 3) foi o achado estromal mais frequente (62%), seguido de fibrose (45%), presença de células de Hofbauer (37%) e espessamento perivascular (30%). Classificamos as placentas em 4 grupos para análise estatística: com inflamação e alteração estromal (63% dos casos), com inflamação sem alteração estromal (15%), com alteração estromal sem inflamação (10%), e com alterações mínimas (12%). Dos 60 recém-nascidos (RN), 13% foram prematuros e 20% nasceram pequenos para idade gestacional (PIG). Microcefalia ao nascimento foi encontrada em 32% dos RN, sendo 28% microcefalia grave. Nós avaliamos 52 pelo menos mais uma vez entre 6 e 12 meses de vida. Alteração neurológica clínica foi observada em 22 bebês (22/59, 37%), e detectada ao exame de imagem de sistema nervoso central em 41% (24/59). Além disso, 36% (21/59) foram diagnosticados com epilepsia. Encontramos em 20% (12/60) pelo menos uma deformidade osteoarticular já presente ao nascimento ou diagnosticada ao longo do ano. Potencial Evocado Auditivo de Tronco Encefálico (PEATE) esteve alterado em 18% (10/55). Também 32% (19/60) tiveram alteração ao exame de fundoscopia. Dos 33 lactentes nascidos assintomáticos e submetidos ao Teste de Bayley III, 18% (6/33) tiveram alteração em pelo menos um domínio. As variáveis estatisticamente significativas em relação aos grupos de acometimento placentário foram peso ao nascimento (p≤0,05) e perímetro cefálico (PC) entre seis e 12 meses (p<0,05). CONCLUSÃO: Em fetos expostos ao ZIKV, placentas com inflamação e alteração estromal estão associadas a baixo peso para idade gestacional ao nascer e reduzido PC após seis meses de vida. De modo inverso, fetos com placentas de alterações mínimas parecem ter menos alterações no desenvolvimento clínico em seu primeiro ano de vida.

INTRODUCTION: Since its entry, Zika virus (ZIKV) has been related to a range of clinical abnormalities in fetuses of infected pregnant women, in Brazil. In addition to the neurological abnormalities, there were also osteoarticular, auditory and ocular alterations described, constituting the current broad spectrum of the Congenital Zika Syndrome. The reason why some infants are severely affected while others are asymptomatic throughout the nursing period is still under investigation. Because it is a congenital infection, some clues to this answer may lie in the analysis of the placenta. OBJECTIVE: To study placental histopathology in vertical infection by ZIKV and its relationship with clinical changes in the first year of life. METHODS: A prospective study of 60 mother-infant binomials with proven ZIKV infection during gestation or perinatal period by RT-qPCR, whose deliveries were performed in a tertiary hospital in Rio de Janeiro, Brazil, where the histopathological analysis of the placenta and the clinical follow-up of the infants up to 12 months of age occurred in the same hospital. RESULTS: ZIKV was more diagnosed in the first trimester of gestation (48%). Almost 80% of the 60 analyzed placentas had inflammatory cells: grade 1 villitis was most frequently found (55%), followed by grade 2 villitis (15%) and high grade villitis (8%). In 22% of the placentas we did not identify villitis. The retardation of the villous maturation (grades 2 and 3) was the most frequent stromal finding (62%), followed by fibrosis (45%), presence of Hofbauer cells (37%) and perivascular thickening (30%). We classified all the placentas in 4 groups for statistical analysis: with inflammation and stromal alteration (63% of all cases), with inflammation without stromal alteration (15%), with stromal alteration without inflammation (10%), and with minimal alterations (12%). Of 60 newborns (NB), 13% were premature and 20% were born small for gestational age. Microcephaly at birth was found in 32% (19/60) of all NB, with 28% of them being severe microcephaly. We could evaluate 52 babies at least once again between 6 and 12 months of life. Clinical neurological abnormalities were observed in 22 infants (22/59, 37%), and abnormalities in CNS imaging test were detected in 41% (24/59). Epilepsy was diagnosed in 36% (21/59). We found that 20% (12/60) presented at least one osteoarticular deformity already present at birth or diagnosed throughout the year. Also, 18% (10/55) presented abnormal BERA examination and 32% (19/60) had ocular fundoscopy exam abnormalities. Of the 33 infants born asymptomatic and submitted to the Bayley III Test, 18% (6/33) had alteration in at least one domain. The variables that were statistically significant in relation to the groups of placental involvement were birth weight (p≤0.05) and CP between six and 12 months (p<0.05). CONCLUSION: Fetuses exposed to ZIKV that present placentas with inflammation and stromal alterations are more likely to develop low birth weight for gestational age and low cephalic perimeter after six months of life. Conversely, fetuses with placentas with minimal alterations appear to have fewer abnormalities in the clinical development during the course of their first year of life.

Morphological features of the human placenta and its free chorionic villi in normal pregnancies and those with diabetes and high blood pressure: literature review / Características morfológicas de la placenta humana y sus vellosidades coriales libres en gestas normales y con diabetes e hipertensión arterial: revisión de la literatura

The most prevalent pathologies during pregnancy, such as hypertension, gestational diabetes mellitus (GDM), and intrauterine growth restriction (IUGR), can determine modifications in macro- and microscopic morphological features of the placenta and its free chorionic villi. In the fetus it may be accompanied by pathological manifestations, with the embryo's future quality of life, and even its viability, at risk. The aim of this work is to perform a review of the morphological alterations that the placenta exhibits in pregnancies with GDM. A search on the topic in the scientific literature and specialized textbooks was carried out. The terms "placenta", "diabetes mellitus gestational" and "gestational diabetes mellitus" were used to define the search. Among the morphological modifications it was found that the placental weight/fetal weight ratio is higher in GDM and is associated mainly with histological changes. The distance between maternal and fetal circulation is increased because of an increase in the chorionic villi on the surface as well as greater thickness of the syncytiotrophoblast basal membrane due to an increased type IV collagen deposition. The stroma between the villi is edematous, which modifies the metabolic and endocrinal function of these placentas. Moreover, the capillary surface is enlarged due to the phenomena of vascular neoformation and a greater penetration of these vessels within the villi. Low oxygen partial pressure (pO2) was detected, which would produce a compensatory hyperplasia of terminal chorionic villi. In GDM the placenta undergoes alterations in its formation, structure, and function. According to the review, these alterations are related to an oxygenation deficiency in the fetus and changes in the transplacental transport of nutrients and other alterations, causing fetal overgrowth by increasing their availability in addition to other consequences to the developing fetus. In the case of high blood pressure during pregnancy, this produces accelerated maturation and rapid aging of the chorionic villi, with the risk of inducing a placental abruption. In addition, placental circulation is reduced by a third, decreasing oxygen saturation in the umbilical vessels and placing the health of the fetus at risk.

Las patologías de la gestación más prevalentes, como hipertensión, diabetes mellitus gestacional (DMG) y restricción del crecimiento uterino, pueden determinar modificaciones en las características morfológicas macro y microscópicas de la placenta y sus vellosidades coriales libres,y en el feto se puede acompañar de manifestaciones patológicas, con riesgo para su calidad de vida futura, e incluso su viabilidad. El objetivo de este trabajo consiste en realizar una revisión acerca de las alteraciones morfológicas que presenta la placenta en gestaciones con DMG. Se llevó a cabo una búsqueda sobre la temática en literatura científica y libros de texto especializados. Se utilizaron los términos "placenta", "diabetes mellitus gestacional" y "gestational diabetes mellitus" para orientar la búsqueda. Entre las modificaciones morfológicas se encontró que la relación peso placentario/peso fetal está aumentado en la DMG y se asocia principalmente a cambios histológicos. La distancia entre la circulación materna y la fetal está aumentada debido a un aumento de la superficie entre las vellosidades coriales, así como al mayor grosor de la membrana basal del sincitiotrofoblasto por un depósito elevado de colágeno tipo IV. El estroma entre las vellosidades se encuentra edematoso lo que va a modificar la función metabólica y endocrina de estas placentas. También hay aumento de la superficie capilar por fenómenos de neoformación vascular y una mayor penetración de estos vasos dentro de las vellosidades. Se detectó baja presión parcial de oxígeno (pO2), que produciría una hiperplasia compensatoria de vellosidades coriónicas terminales. En la DMG la placenta experimenta alteraciones en su formación, estructura y función. Según lo revisado, estas alteraciones están relacionadas con déficit en la oxigenación del feto, cambios en el transporte transplacentario de los nutrientes y otras alteraciones, ocasionando sobrecrecimiento fetal por aumento de su disponibilidad, entre otras consecuencias al feto en desarrollo. Y en el caso de la hipertensión arterial durante la gestación produce una maduración acelerada y envejecimiento rápido de las vellosidades coriales, con el riesgo de inducir un desprendimiento prematuro de placenta. Además se reduce la circulación placentaria en un tercio, disminuyendo la saturación de oxígeno en los vasos umbilicales del, poniendo en riesgo la salud del feto.

Corangioleiomioma placentario / Placentary chorangio-leiomyoma

Los corangiomas son los tumores placentarios no trofoblásticos más frecuentes; generalmente aparecen como hallazgos al momento del alumbramiento. La presencia de leiomiomas en las placentas también ha sido descripta esporádicamente, siendo por lo general tumores maternos uterinos incorporados a la placenta durante la gestación. En este trabajo se informa un caso muy inusual de lesión mesenquimática, localizada en la cara fetal placentaria, caracterizada por la combinación de rasgos histopatológicos e inmunohistoquímicos de corangioma y leiomioma. Se encontró un solo caso informado en la bibliografía científica internacional con estas características, denominado "corangioleiomioma". En nuestro conocimiento, el caso aquí expuesto es el primero comunicado en nuestro país.

Chorangiomas are the most common non-trophoblastic tumors, generally appearing as incidental findings at the moment of delivery. The presence of leiomyomas inside placental parenchyma has been also described sporadically. In these cases, leiomyomas were primary maternal uterine neoplasms incorporated into the placenta during pregnancy. This case report presents a very unusual case of mesenchymal lesion, located in the fetal surface of the placenta, characterized by combined histopathologic and immunohistochemical features of chorangioma and leiomyoma. A single case reported with these characteristics was found in the international scientific literature, named as "chorangioleiomyoma". To our knowledge, this is the first case reported in our country.

Aspectos morfocuantitativos de las vellosidades coriales libres en gestas normales, con diabetes, hipertensión arterial y restricción del crecimiento intrauterino / Morphoquantitative characteristics of free corial vellosities in normal births, with diabetes, hypertension and restriction of intrauterine growth

Las patologías de la gestación como la hipertensión, diabetes mellitus gestacional, o restricción del crecimiento intrauterino, pueden determinar modificaciones en las características morfológicas macro y microscópicas de la placenta y sus vellosidades coriales libres, y en el feto se puede acompañar de manifestaciones patológicas, con riesgo para su calidad de vida futura, e incluso su viabilidad. El objetivo de este trabajo consistió en describir aspectos morfométricos e histológicos de las vellosidades coriales libres en gestas normales, con diabetes e hipertensión arterial. Se utilizaron 30 placentas humanas y fueron separadas, según presencia o ausencia de patologías en el embarazo, en tres grupos: Normal (N), Síndrome Hipertensivo del Embarazo (SHE), Diabetes (D) y Restricción del Crecimiento Intrauterino (RCIU). Se usó ficha para registrar peso placentario y del recién nacido Todas las muestras fueron fijadas en formalina tamponada al 10 %. De cada una fueron extraídas 5 muestras, obteniendo 25 cortes por cada placenta. Posteriormente, fueron teñidas con H&E, Azul Alcián y Tricrómico de Masson. Además, se efectuó el análisis histológico y morfométrico (ImageJ®) de las vellosidades coriales. El análisis estadístico fue realizado utilizando ANOVA. Entre los cambios morfológicos, se encontró una relación peso placentario/peso del recién nacido aumentada en la Diabetes Mellitus Gestacional asociada a cambios histológicos. No hubo cambios morfométricos significativos entre placentas N, SHE y D. Hubo un aumento en el número de vasos coriales en placentas del grupo D (P < 0,05) y de la superficie entre las vellosidades coriales. En el grupo SHE hubo aumento moderado de nudos sinciciales y presencia de fibrina en el estroma. Las placentas con Diabetes Mellitus Gestacional experimentan alteraciones histológicas, como consecuencia de cambios estructurales y funcionales. Además, el aumento de vasos sanguíneos en placentas con diabetes se produce por neoformación vascular y mayor penetración de vasos sanguíneos dentro de las vellosidades. En el caso del SHE las alteraciones placentarias se relacionan con la gravedad de la enfermedad.

Gestational pathologies such as hypertension, gestational diabetes mellitus and restriction of intrauterine growth can determine changes in the macro and microscopic morphological characteristics of the placenta and its free chorionic villi. In the fetus it can be accompanied by pathological manifestations with risk to its viability and future quality of life. The aim of this work was to describe morphometric and histological aspects of free chorionic villi in normal pregnancies associated with diabetes, hypertension and restriction of intrauterine growth. Thirty human placentas were used and were separated into three groups: Normal (N), Hypertensive Pregnancy Syndrome (SHE), Diabetes (D), and Restriction of Intrauterine Growth (RIG) according to evident pathologies or absence thereof during pregnancy. Tab was used to record placental and newborn weight. All samples were fixed in 10 % buffered formalin. From each, 5 samples were extracted, obtaining 25 cuts for each placenta. Subsequently, they were stained with H & E, Alcian Blue and Masson's Trichrome. In addition, histological and morphometric analysis (ImageJ®) of the chorion villus was carried out. Statistical analysis was performed using ANOVA. Among the morphological changes, an increased placental weight / weight ratio of the newborn was found in Gestational Diabetes Mellitus associated with histological changes. There were no significant morphometric changes between placentas N, SHE and D. There was an increase in the number of corial vessels in placentas of group D (P <0.05) and of the surface between the chorion villi. In the SHE group there was a moderate increase in syncytial nodes and presence of fibrin in the stroma. Placentas with Gestational Diabetes Mellitus experience histological alterations, as a consequence of structural and functional changes. In addition, the increase of blood vessels in placentas D is produced by vascular neoformation and increased penetration of blood vessels into the villi. In the case of SHE, placental alterations are related to the severity of the disease.

Histomorphological study of placenta in gestational diabetes mellitus / Estudio histomorfológico de la placenta en diabetes mellitus gestacional

Evidence from the literature shows that well-controlled glucose levels during pregnancy are usually associated with normal placental morphology. The aim of this study was to identify the lacental changes attributed to maternal hyperglycemia. A total of 20 placentae were selected for study from a tertiary care medical center in Makkah city, Saudi Arabia. Out of 20, 10 placentae were from patients diagnosed with GDM based on IADSPG criteria, and 10 placentae were from patients with normal pregnancies without GDM. The morphometric measurements were recorded. The mean weight of GDM placentae were more than the normal placentae. Upon histopathology, significant changes such as syncytial knots, cytotrophoblastic cell proliferation, fibrinoid necrosis, stromal fibrosis, and hyalinized villi were observed in GDM placentae. GDM produces significant morphological alterations in the placentae, which might affect the developing fetus.

La evidencia de la literatura muestra que niveles de glucosa bien controlados durante el embarazo generalmente se asocian con una morfología placentaria normal. El objetivo de este estudio fue identificar los cambios placentarios atribuidos a la hiperglucemia materna. Un total de 20 placentas fueron seleccionadas para un estudio en un centro médico de atención terciaria en la ciudad de La Meca, Arabia Saudita. De 20 placentas, 10 de estas fueron de pacientes diagnosticadas con diabetes mellitus gestacional (DMG) según los criterios de IADSPG, y 10 placentas fueron de pacientes con embarazos normales sin DMG. Las mediciones morfométricas fueron registradas. El peso medio de las placentas GDM fue mayor que la placenta normal. Tras la histopatología, se observaron cambios significativos tales como nudos sincitiales, proliferación celular citotrofoblástica, necrosis fibrinoide, fibrosis estromal y vellosidades hialinizadas en placenta con DMG. La DMG produce alteraciones morfológicas significativas en las placentas, que pueden afectar al desarrollo del feto.

Expression of endothelin-1 and Ki-67 in normotensive and severe preeclamptic placentas / Expresión de endotelina-1 y Ki-67 en placentas normotensas y preeclampsia severa

SUMMARY: Severe preeclampsia (HELLP syndrome) is a life-threatening pregnancy complication, usually a severe form of preeclampsia. In this study, we aimed to examine histopathologic changes and Endothelin-1 and KI-67 expression levels by immunohistochemical methods in severe preeclamptic placentas. Severe preeclampsia and obstetric characteristics and biochemical and hematological characteristics of healthy subjects were compared. Placenta sections were stained with hematoxylin-eosin for histopathological examination. In the histopathological examination of severe preeclamptic placenta, degeneration in synaptic and cytotrophoblastic cells, increase in insidious knots, fibrinoid necrosis, degeneration in endothelial cells, calcification and hyaline villous stains were observed. In the severe preeclampsia group, Ki-67 expression increased in decidua cells and inflammatory cells, while endothelial cells in the vessel wall and inflammatory cells in the villus and intervillous spaces increased. It is thought that angiogenetic and cellular proliferation is induced in a co-ordinated manner and significantly influences fetal development.

RESUMEN: La preeclampsia severa (síndrome de HELLP) es una complicación del embarazo potencialmente mortal, generalmente una forma grave de preeclampsia. En este estudio, nuestro objetivo fue examinar los cambios histopatológicos y los niveles de expresión de Endotelina-1 y Ki-67 mediante métodos inmunohistoquímicos en placentas preeclámpsicas graves. Se compararon la preeclampsia grave y las características obstétricas, además de las características bioquímicas y hematológicas de pacientes sanas. Las secciones de placenta se tiñeron con hematoxilina-eosina para examen histopatológico. En el examen histopatológico de placenta preeclampsia severa, se observó la degeneración en células sinápticas y citotrofoblásticas, un aumento de nudos insidiosos, necrosis fibrinoide, degeneración en las células endoteliales,calcificación y manchas vellosas hialinas. En el grupo de preeclampsia grave, la expresión de Ki-67 aumentó en células deciduas y células inflamatorias, mientras que las células endoteliales en la pared del vaso, y las células inflamatorias en las vellosidades y los espacios intervellosos aumentaron. Se cree que la proliferación angiogenética y celular se induce de forma coordinada y que influye significativamente en el desarrollo fetal.

Placental weight and birth weight to placental weight ratio in monochorionic and dichorionic growth-restricted and non-growth-restricted twins

OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65) and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162) placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022) and dichorionic (p<0.001) twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36) or dichorionic (p=0.68) twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions. CONCLUSION: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies.

Morfología de la placenta en recién nacidos con defecto congénito / Morphology of the placenta in newborns with congenital defects

El objetivo del estudio fue comparar el índice de madurez placentaria y las alteraciones histopatológicas en placentas de recién nacidos/óbitos con y sin defecto congénito (DC). Se realizó un estudio tipo casos y controles. Se incluyeron n=25 casos yn=50 controles sin DC. Los casos se clasificaron de acuerdo a la presencia de DC aislado (n=17) omúltiple (n=8). Se incluyeron recién nacidos/óbitos (RN) con una edad gestacional (EG) > 20 semanas. Se excluyeron embarazos gemelares. Se recolectó información sobre las características clínicas del producto y de la madre, antropometría del RN y su evaluación de APGAR. Se examinó la placenta, macroscópica y microscópicamente, para determinar la presencia y extensión de alteraciones histopatológicas. Se determinó el índice de madurez placentaria (IMP), calculado dividiendo el número de membranas vásculo sinciciales en 1 mm2 entre el grosor de las mismas (µ). El IMP (media ±DE) fue de 27.77±14 en el grupo de controles, 30.31±12 en el grupo de casos aislados y 16.76± 1 en el grupo de DC múltiple (p<0.05).El resto de las variables evaluadas no mostraron diferencias significativas entre grupos. En conclusión este trabajo muestra una menor madurez placentaria asociada con la presencia de DC múltiple.

The objective of the study was to compare the placental maturity index (PMI) and pathohistological alterations of placentas from newborn/stillborns (NB) with or without congenital defects (CD). A case control study was carried out. N=25 CD cases and n=50 controls without CD were included. Cases were classified according to the presence of simple (n=17) or multiple (n=8) CD. Newborn/stillborns with gestational age >20 weeks were included. Twin pregnancies were excluded. We collected information on clinical characteristics of the NB and the mother, NB anthropometry and APGAR score. The placenta was macro and microscopically examined to determine the presence and extension of histological alterations. The PMI was obtained by dividing the number of vasculo-syncytial membranes in 1 mm2, by their thickness (µ). The PMI (Mean ± SD) was 27.77 ± 14 in the control group, 30.31 ± 12 in the group diagnosed with simple CD, and 16.76 ± 1 in the group diagnosed with multiple CD (p<0.05. The rest of the assessed variables did not show significant difference between groups. In conclusion, this work shows a lower placental maturity associated with the presence of multiple CD.

Fetal thrombotic vasculopathy: A case report and literature review / Vasculopatia trombótica fetal: relato de caso e revisão da literatura

Summary Introduction: Fetal thrombotic vasculopathy is a recently described placental alteration with varying degrees of involvement and often associated with adverse perinatal outcomes. The diagnosis is made histologically and therefore is postnatal, which makes it a challenge in clinical practice. Method: Case report and review of literature on the subject. Results: The present case refers to a pregnant woman presenting fetal growth restriction, with poor obstetrical past, and sent late to our service. Even with weekly assessments of fetal vitality (fetal biophysical profile and Doppler velocimetry) and prenatal care, the patient progressed with fetal death at 36 weeks and 1 day. There was no association with inherited and acquired thrombophilia. Pathological examination of the placenta revealed fetal thrombotic vasculopathy. Conclusion: The fetal thrombotic vasculopathy may be associated with adverse perinatal outcomes including fetal death, but much remains to be studied regarding its pathogenesis. Diagnosis during pregnancy is not possible and there is still no proven treatment for this condition. Future studies are needed so that strategies can be developed to minimize the impact of fetal thrombotic vasculopathy.

Resumo Introdução: a vasculopatia trombótica fetal é uma alteração placentária recentemente descrita, com espectro variado de acometimento e, muitas vezes, associada a resultado perinatal adverso. Trata-se de diagnóstico histopatológico e, portanto, pós-natal, o que a torna um desafio para a prática clínica. Método: apresentação de um relato de caso e revisão da literatura. Resultados: o caso apresentado é de uma gestante com restrição do crescimento fetal, encaminhada tardiamente ao serviço, com histórico obstétrico ruim. Apesar da avaliação semanal da vitalidade fetal (perfil biofísico fetal e dopplervelocimetria) e dos cuidados pré-natais, o caso evoluiu a óbito fetal com 36 semanas e 1 dia. Não houve associação com trombofilias hereditárias e adquiridas. O anatomopatológico da placenta revelou vasculopatia trombótica fetal. Conclusão: sabe-se que a vasculopatia trombótica fetal pode estar associada a resultado perinatal adverso, incluindo óbito fetal. Ainda há muito a ser estudado acerca de sua etiopatogenia. Não é possível o diagnóstico durante a gestação e não existe ainda qualquer tratamento comprovado para essa condição. Estudos futuros são necessários para que estratégias que minimizem o impacto da vasculopatia trombótica fetal sejam desenvolvidas.

Frequency and risk factors for the birth of small-for-gestational-age newborns in a public maternity hospital / Frequência e fatores de risco para o nascimento de recém-nascidos pequenos para idade gestacional em maternidade pública

ABSTRACT Objective: To determine the frequency and risk factors of small-for-gestational-age newborns in a high-risk maternity. Methods: This is an observational, cross-sectional, and case-control study, conducted in a public tertiary care maternity hospital. Data from 998 newborns and their mothers were collected through interviews and review of medical records and prenatal care cards. Some placentas underwent histopathological analysis. The variables of small-for-gestational-age and non-small-for-gestational-age newborns and of their mothers were statistically compared by means of Student's t test, Fisher's exact test, and odds ratio. The significance level used was 0.050. Results: There was a 17.9% frequency of small-for-gestational-age newborns. The statistically significant factors associated with the birth of these babies were female sex (p=0.012); positive history of another small-for-gestational-age child (p=0.006); inadequate prenatal care (p=0.019); smoking (p=0.003); hypertensive disorders of pregnancy (p=0.007); placental bleeding (p=0.009) and infarction (p=0.001). Conclusion: In the population studied, the frequency of small-for-gestational-age newborns was high and associated with sex, inappropriate prenatal care, presence of maternal diseases and addictions, and placental abnormalities.

RESUMO Objetivo: Determinar a frequência e os fatores de risco de recém-nascidos pequenos para idade gestacional em uma maternidade de alto risco. Métodos: Trata-se de um estudo observacional, transversal e caso-controle, realizado em maternidade pública de nível terciário. Foram levantados dados de 998 recém-nascidos e de suas respectivas mães por meio de entrevista e análise de prontuários e de cartões do pré-natal. Algumas placentas foram submetidas à análise anatomopatológica. As variáveis dos recém-nascidos pequenos e não pequenos para idade gestacional e de suas respectivas mães foram comparadas estatisticamente pelo teste paramétrico t de Student, pelo teste exato de Fisher e por odds ratio. O nível de significância adotado foi de 0,050. Resultados: A frequência de recém-nascidos pequenos para idade gestacional foi de 17,9%. Os fatores com significado estatístico associados ao nascimento desses bebês foram sexo feminino (p=0,012); história positiva para filho anterior pequeno para idade gestacional (p=0,006); realização de pré-natal inadequado (p=0,019); tabagismo (p=0,003); doença hipertensiva específica da gestação (p=0,007); hemorragia (p=0,009) e infarto (p=0,001) placentários. Conclusão: Na população estudada, a frequência de recém-nascidos pequenos para idade gestacional foi elevada e relacionada ao sexo, à inadequação do pré-natal, à presença de doenças e vícios maternos e às alterações placentárias.

Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature

We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.