WD repeat domain 5 promotes the development of late-onset preeclampsia by activating nuclear factor kappa B

Purpose: Over-activation of nuclear factor kappa B (NF-κB) was proven to be involved in the pathogenesis of preeclampsia. However, its regulation mechanism is not clear yet. This paper explored the role of WD repeat domain 5 (WDR5) in the development of late-onset preeclampsia and its relationship with NF-κB. Methods: WDR5 expression was detected in normal placentas and placentas from late-onset preeclampsia patients. CCK-8 and colony formation assays were conducted to appraise the proliferative ability of trophoblast. Migration and invasion were observed by wound healing and transwell assays. The interaction between WDR5 and NF-κB inhibitor I-kappa-B-alpha (IkBa) was verified by Co-immunoprecipitation analysis. Immunofluorescence was used to analyze the activation of NF-κB. Finally, we tested the role of WDR5 using the mice late-onset preeclampsia model. Results: WDR5 was highly expressed in the placentas of late-onset preeclampsia patients. WDR5 overexpression suppressed cell proliferation, migration, and invasion in trophoblast. WDR5 could interact with IkBa to activate NF-κB. Knockdown of NF-κB counteracted the anti-proliferative and anti-metastatic effects of WDR5 overexpression in trophoblast. In-vivo studies suggested that targeting WDR5 combated late-onset preeclampsia development. Conclusions: Our finding provides new insights into the role of WDR5 in late-onset preeclampsia development.

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.

The role of circular RNA circ_0008285 in gestational diabetes mellitus by regulating the biological functions of trophoblasts

BACKGROUND: Circular RNAs (circRNAs) has emerged as vital regulator involved in various diseases. In this study, we identified and investigated the potential circRNAs involved in gestational diabetes mellitus (GDM). METHODS: High-throughput sequencing was used to collect the plasma circRNAs expression profiles of GDM patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to measure the expressions of circ_0008285 and circ_0001173 in the plasma specimens. The Pearson's correlation test was employed to assess the correlation between 2 circRNAs expression and the clinicopathologic data. Two circRNAs expression was verified in high glucose (HG)-induced HTR-8/SVneo cells. MTS, transwell assay was used to evaluate the effects of circ_0008285 expression on HG-induced HTR-8/SVneo cells. The network of circ_0008285 was constructed using cytocape. RESULTS: In GDM patients, the expression of circ_0008285 was significantly upregulated, while that of circ_0001173 was decreased. Circ_0008285 was significantly correlated with the total cholesterol and LDL-C levels. Circ_0001173 was significantly correlated with glycated hemoglobin. HG promoted the proliferation, invasion, and migration in HTR-8/SVneo cells, while the knockdown of circ_0008285 exerted reverse effects. In addition, network construction exhibited that circ_0008285 had 45 miRNA binding sites, which correlated with 444 mRNA. CONCLUSIONS: circ_0008285 plays an important role and provides a clue for the usage of therapeutic targets in the development of GDM.

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

OBJECTIVE: This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). METHODS: Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. RESULTS: Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. CONCLUSION: miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

Long non-coding RNA FAM99A modulated YAP1 to affect trophoblast cell behaviors in preeclampsia by sponging miR-134-5p

Preeclampsia (PE) is a complex pregnancy syndrome. Convincing evidence indicates that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of PE. This research mainly investigated the mechanism of family with sequence similarity 99 member A (FAM99A) in PE. The expressions of FAM99A, miR-134-5p, and YAP1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis, migration, and invasion were detected by flow cytometry or transwell assay. The interaction between miR-134-5p and FAM99A or YAP1 was confirmed by dual-luciferase reporter assay. The protein expression of YAP1 was determined by western blot assay. FAM99A and YAP1 were significantly up-regulated, and miR-134-5p was significantly down-regulated in PE tissues (n=30). miR-134-5p was verified as a candidate of FAM99A and YAP1. FAM99A promoted cell metastasis, but reduced apoptosis in HTR8/SVneo cells by regulating miR-134-5p. miR-134-5p down-regulated YAP1 expression to suppress cell metastasis, while it induced apoptosis in HTR8/SVneo cells. FAM99A positively modulated YAP1 expression by sponging miR-134-5p. FAM99A modulated YAP1 to accelerate cell migration and invasion, and inhibited cell apoptosis in PE cells by sponging miR-134-5p. The novel regulatory network may shed light on the pathogenesis of PE.

Expresión de calreticulina en placenta canina / Calreticulin expression in canine placenta

La placenta es un anexo embrionario de los mamíferos que tiene por función principal el intercambio de nutrientes y gases y proteger al concepto de un potencial daño inmune provocado por diferencias alogénicas en los Complejos Principales de Histocompatibilidad paternos. Se han descrito diversas proteínas asociadas a su función, siendo Calreticulina una de ellas. Si bien existen estudios de la presencia de Calreticulina en placenta humana, no existen reportes de esta proteína en la placenta canina. Se obtuvieron muestras de placenta canina de las que se extrajo el contenido proteico total y se determinó la presencia de Calreticulina por western blot e inmunohistoquímica. Los resultados mostraron presencia de Calreticulina en placenta canina con un peso molecular aparente de 60 kDa, concordante con lo descrito para la molécula por otros autores. El análisis inmunohistoquímico mostró que Calreticulina canina está presente principalmente en el trofoblasto de las vellosidades, no existiendo diferencias en cuanto a su localización al compararla con placenta humana, pese a sus diferencias morfológicas e histológicas. Esta información permitirá establecer un protocolo estandarizado de extracción de Calreticulina desde placenta, así como orientar acerca de los posibles roles de esta molécula en la placenta.

The placenta is an embryonic organ present in mammals, whose main functions are the exchange of nutrients and gases and to protect the fetus from potential immune damage mediated by paternal and maternal allogeneic differences in the Major Histocompatibility Complex. Several proteins associated with its function have been described, being Calreticulin one of them. Although there are studies on the presence of Calreticulin in human placenta, there are no reports of this protein in canine placenta. Samples from canine placenta were obtained, proteins extracted and Calreticulin was subsequently detected by western blot and immunohistochemistry. The results showed the presence of Calreticulin in canine placenta with an apparent molecular weight of 60 kDa, in agreement with the results from other authors. The immunohistochemical analysis showed that canine Calreticulin is present mainly in the trophoblast of the villi, and there is no difference in its localization when compared with a blood-filled placenta such as human one, despite its morphological and histological differences. We also propose a standardized protocol for the extraction of Calreticulin from placenta, given its abundant expression in this organ. Future studies are aimed at elucidating possible roles of this protein in placenta.

Factores de riesgo de la enfermedad trofoblástica gestacional: Hospital Central Universitario Dr. Antonio María Pineda / Risk factors of gestational trofoblastic disease: Hospital Central Universitario Dr. Antonio María Pineda

La Enfermedad Trofoblástica Gestacional (ETG) es una patología de la primera mitad del embarazo caracterizada por una degeneración hidrópica de las vellosidades coriales que abarca la placenta y el resto del complejo ovular; es generalmente benigna pero puede malignizarse y distribuirse hacia otros tejidos. Se realizó un estudio descriptivo transversal con recolección retrospectiva de datos cuyo objetivo fue determinar los factores de riesgo de la ETG en pacientes que acudieron al Servicio de Emergencia Gineco-Obstétrica del Hospital Dr. Antonio María Pineda durante el período enero-agosto 2018. Dentro de la muestra se incluyeron las historias clínicas de 55 pacientes siendo la mayor parte mujeres menores de 28 años, de procedencia urbana, multigestas, sin antecedentes de aborto espontáneo o embarazo molar y sin uso de dispositivos intrauterinos o uso prolongado de anticonceptivas orales. En conclusión, se hace necesario un mayor seguimiento a mujeres embarazadas jóvenes con las características anteriormente expuestas con la finalidad de realizar un diagnóstico temprano de la enfermedad y de esta manera implementar medidas que garanticen su salud y vida(AU)

Gestational Trophoblastic Disease (TSG) is a pathology of the first half of pregnancy characterized by a hydropic degeneration of the chorionic villi that spans the placenta and the rest of the ovular complex; it is usually benign, but it can become malignant and spread to other tissues. A descriptive transversal study with retrospective review of medical charts was performed in order to determine the risk factors for TSG of patients evaluated at the Servicio de Emergencia Gineco-Obstétrica of the Hospital Dr. Antonio Maria Pineda during the January-August 2018 period. Fifty-five medical charts were reviewed. Results show that TSG was more common in women < 28 years old that lived in urban areas, which had several pregnancies, with no prior history of spontaneous abortion, molar pregnancy, use of intrauterine devices or prolonged use of contraceptive pills. In conclusion, a follow-up of young pregnant women is necessary in order to have an on time diagnosis of this disease as well as promote measures that guarantee the patients' health as well as her life(AU)

Interacción endometrio trofoblasto, en la implantación humana: revisión de la literatura / Endometrium-trophoblast interaction in human implantation: review of literature

Un embarazo exitoso requiere de una serie de interacciones mediadas por factores hormonales, moleculares y fenómenos de inmunomodulación. Una de estas interacciones es la que ocurre entre el endometrio y el blastocito, previo y durante el proceso de implantación. El objetivo de esta revisión bibliográfica es complementar lo descrito en la literatura clásica de embriología humana sobre interacción de endometrio-blastocito. La búsqueda bibliográfica se realizó en la base de datos MEDLINE usando los términos en inglés "implantation", "endometrium" y "embryo"; además se realizó una búsqueda manual, que incluyó artículos de revistas no indexadas, libros de texto y atlas. Se consideraron criterios de inclusión y exclusión para la selección de los artículos y otros recursos bibliográficos. Entre los criterios de inclusión se consideraron estudios realizados en humanos, artículos de revisión y experimentación, publicados en los últimos 5 años. Como criterios de exclusión se consideraron artículos que utilizaran animales, estudios sobre fertilidad in vitro, patologías asociadas y artículos no relacionados al tema. Una vez completada la selección, se examinaron los textos completos, en los cuales se aplicaron nuevamente los criterios de exclusión. La búsqueda arrojó un total de 560 artículos, cuyo análisis de los títulos y resúmenes resultó en 475 trabajos excluidos, a partir de los diferentes criterios de exclusión antes descritos. Por lo tanto, se obtuvieron 85 artículos, en los cuales se realizó el análisis del texto completo. De estos artículos, se obtuvieron un total de 34 estudios y los contenidos seleccionados en esta revisión fueron: Endometrio, Interacción endometrio trofoblasto, Aposición, Adhesión y Migración-Invasión. Durante la implantación se genera una interacción entre el endometrio y el trofoblasto, con la participación de moléculas reguladoras de proliferación y diferenciación, como factores hormonales, moleculares y de expresión génica. Sin embargo, los mecanismos específicos de acción e interacción deben continuar siendo investigados, para responder interrogantes en el ámbito del crecimiento y desarrollo humano.

A successful pregnancy requires a series of interactions, mediated by hormonal, molecular and immunomodulation phenomena. One of these interactions is between the endometrium and the blastocyst, before and during the implantation process. The objective of this literature review is to complement what is described in the classic human embryology literature on endometrial-blastocyst interaction. The bibliographic search was carried out in the MEDLINE database using the terms "implantation", "endometrium" and "embryo", and a manual search was carried out, which included articles from non-indexed journals, textbooks and atlases. Inclusion and exclusion criteria were considered for the selection of articles and other bibliographic resources, including human studies, review and experimentation articles, published in the last 5 years. Articles with animals as experimental subjects, in vitro fertility studies, associated pathologies and articles not related to the subject were excluded. When the selection was completed, the complete texts were examined, in which the exclusion criteria were applied again The search yielded a total of 560 articles, whose analysis of titles and abstracts resulted in 475 excluded works, in relation to different exclusion criteria described above. Therefore, 85 articles were obtained, in which the complete text analysis was performed. From these articles, a total of 34 studies were obtained and the contents selected in this review were: Endometrium, Endometrium trophoblast, Aposition, Adhesion and Migration-Invasion. During the implantation, aninteraction between the endometrium and the trophoblast is generated, with the participation of regulatory molecules of proliferation and differentiation, such as hormonal, molecular and gene expression factors. However, the specific mechanisms of action and interaction must continue to be investigated, to answer questions in the field of human growth and development.

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.

O feto é um ser alogênico de sucesso / The fetus is a successful allogeneic being

O feto é um ser alogênico de sucesso. O feto é um aloenxerto natural bem tolerado pelo organismo materno. Vários fatores contribuem para a tolerância materna ao feto: 1. O útero é um local do corpo imunologicamente privilegiado, protegido por uma barreira tecidual não imunogênica; 2. A promoção de uma resposta imunossupressora local pela mãe: a. A molécula HLA-G do MHC de classe Ib, expressa nas células da placenta, impede que as células NK matem a placenta; b. A catabolização do aminoácido essencial triptofano pela placenta impede que as células T da mãe tenham acesso ao feto; c. A secreção das citocinas TGF-ß, IL-4 e IL-10, pelo epitélio uterino e trofoblasto, tende a suprimir as respostas das células T da mãe; d. A secreção das citocinas TGF-ß e IL-10, pelas células T reguladoras, também inibe as respostas de células T maternas.(AU)

The fetus is a successful allogeneic being. The fetus is a natural allograft well tolerated by the maternal organism. Several factors contribute to maternal fetal tolerance: 1. The uterus is an immunologically privileged body site, protected by a non-immunogenic tissue barrier. 2. Promoting a local immunosuppressive response by the mother: a. The MHC class Ib HLA-G molecule, expressed on placental cells, prevents NK cells from killing the placenta; b. The catabolization of the essential amino acid tryptophan by the placenta prevents the mother's T cells from accessing the fetus; c. Secretion of TGF-ß, IL-4 and IL-10 cytokines by the uterine and trophoblast epithelium tends to suppress the T-cell responses of the mother; d. Secretion of TGF-ß and IL-10 cytokines by regulatory T cells also inhibits maternal T cell responses.(AU)

Enfermedad trofoblastica gestacional / Gestational trophoblastic disease

Resumen La enfermedad trofoblástica gestacional engloba un conjunto de patologías con potencial maligno y neoplásicas propiamente, las cuales pueden ser adquiridas tras la gestación. Aunque estos tumores abarcan menos del 1% de los tumores ginecológicos, representan una amenaza para la vida de las mujeres en edad reproductiva. Es importante que los médicos comprendan su etiología, evolución natural y manejo, debido a su alto potencial de curación con la posibilidad de preservar la función reproductiva si se diagnostica a tiempo y se trata adecuadamente según sus criterios de riesgo y pronóstico.

Abstract The gestational trophoblastic disease englobes a set of neoplastic pathologies and pathologies with malignant potential, which can be acquired after gestation. Even though these tumors include less than 1% of gynecological tumors, they represent a threat to the life of women in reproductive age. It is important that physicians understand its etiology, natural evolution and control. If it is diagnosed on time and treated appropriately according to its risk and prognosis criteria, there's a high healing potential including the ability of preserving reproductive function.

Papel da Apoptose em Obstetrícia / Role of Apoptosis in Obstetrics

Apoptose, ou morte celular programada, é um mecanismo fisiológico universal entre mamíferos que regula o equilíbrio entre proliferação e morte celular a fim de manter a homeostase tecidual. Nesse processo, a apoptose poderá ser iniciada intrinsicamente por via mitocondrial ou, extrinsecamente, mediada por sinalização via receptor de morte ou em resposta a elementos exógenos como citocinas e processos não excludentes, complementares e com ativação cruzada. As moléculas envolvidas no controle das vias de ativação da apoptose são as proteínas anti, pró-apoptóticas e caspases. Esse fenômeno biológico, além de desempenhar um papel importante no controle de diversos processos vitais, está associado a inúmeras complicações da gravidez como toxemia, crescimento intrauterino restrito, parto pré-termo, diabetes gestacional, abortamento, gravidez ectópica e a transformação maligna da mola hidatiforme. No denominador comum dessas doenças está o desconhecimento de sua etiopatogenia e o desenvolvimento/funcionamento placentário anormal. Compreender todas essas alterações deverá interessar não apenas ao pesquisador dessas moléstias, mas também aos clínicos que tratam essas doenças no intuito de se incorporar novas tecnologias na rotina médica e na melhoria das perspectivas prognósticas e terapêuticas dentro da obstetrícia.(AU)

Apoptosis, or programmed cell death, is a universal physiological mechanism in mammals, which regulates the balance between cell proliferation and death in order to maintain tissue homeostasis. In this process, apoptosis can be initiated intrinsically or extrinsically by mitochondrial pathway, mediated by death receptor signaling or in response to exogenous factors such as cytokines and processes not mutually exclusive, complementary and cross-activation. The molecules involved in the control of apoptosis activation pathways are anti and pro-apoptotic proteins as well as caspases. This biological phenomenon, besides play an important role in the control of many vital processes, is associated with many complications of pregnancy such as toxemia, intrauterine growth, preterm birth, gestational diabetes, miscarriage, ectopic pregnancy and malignant in transformation hydatiform mole. The common denominator of these diseases is the lack of knowledge about its pathogenesis and development/abnormal placental function. Understand all these changes should interest not only to the researchers, but also for clinicians who treat these diseases in order to incorporate new technologies in the medical routine and in improving prognostic and therapeutic perspectives in obstetrics.(AU)

Serum concentration of vascular endothelial growth factor and depth of trophoblastic invasion in ampullary ectopic pregnancy

OBJECTIVE: To evaluate the association between the depth of trophoblastic infiltration and serum vascular endothelial growth factorconcentration in patients with an ampullary pregnancy. METHODS: This prospective cross-sectionalstudy involved 34 patients with an ampullary ectopic pregnancy who underwent salpingectomy between 2012 and 2013. Maternal serum vascular endothelial growth factor concentrations were measured using Luminex technology. Trophoblastic invasion was classified histologically as follows: stage I, limited to the tubal mucosa; stage II, reaching the muscle layer; and stage III,involving the full thickness. The qualitative data were compared using Fisher's exact test. The nonparametric Kruskal-Wallis and Mann-Whitney tests were used to evaluate differences in serum vascular endothelial growth factor among the degrees of trophoblastic invasion. ROC curves were constructed to determine vascular endothelial growth factor cut-off values that predict the degree of tubal invasion based on the best sensitivity and specificity. RESULTS: Eight patients had stage I trophoblastic invasion, seven had stage II, and 19 had stage III. The median serum vascular endothelial growth factorconcentration was 69.88 pg/mL for stage I, 14.53 pg/mL for stage II and 9.08 pg/mL for stage III, with a significant difference between stages I and III. Based on the ROC curve, a serum vascular endothelial growth factor concentration of 25.9 pg/mL best differentiated stage I from stages II and III with asensitivity of 75.0%, specificity of 76.9%, and area under the curve of 0.798. CONCLUSIONS: The depth of trophoblastic penetration into the tubal wall isassociated with serum vascular endothelial growth factor concentration in ampullary pregnancies.

Glicanos de la vellosidad trofoblástica en la anemia ferropénica y la preeclampsia grave / Glycans in villus trophoblast in iron deficiency anemia and early-onset severe preeclampsia

Glycoproteins attached to cell membrane of syncytiotrophoblast are in close contact with maternal blood, thus these molecules could participate in cell-to-cell communication and biological functions involving ligand-receptors in the maternal-fetal interphase. The attached glycans are involved in the stability, folding and exportation of the protein towards the cell membrane. The objective of this study was to characterize the glycan profile of third trimester placental villi obtained from pregnant women with early-onset severe preeclampsia and gestational anemia compared with normal pregnant women. Protein extracts from placental villi were used in lectin blot assays. -2,3 N- and O-linked sialic acid was over-expressed in villous of severe preeclamptic placentas measured by MAA lectin staining. High mannose glycans and Gal-GlcNAc patterns were also increased in severe preeclampsia compared with the other groups. These findings can explain changes in the cell membrane expression of glycoproteins.

Introducción: Las glicoproteínas de la membrana del sincitiotrofoblasto (STB) se encuentran en contacto con la sangre materna, por lo que pueden participar en la comunicación en la interface materno-fetal. Objetivo: caracterizar patrones de glicanos de la vellosidad trofoblástica de mujeres sanas, anémicas por deficiencia de hierro y preeclámpticas graves de inicio temprano. Materiales y métodos: se obtuvieron extractos proteínicos de vellosidad placentaria de tercer trimestre y se determinó la expresión de patrones de glicanos, usando lectinas. Para la comparación de los grupos se utilizó la prueba de Kruskal-Wallis. Resultados: Se encontró una sobreexpresión en los patrones de glicosilación Gal-GlcNAc, manosa y ácido siálico α2-3 en el grupo con preeclampsia. Conclusiones: El aumento en los patrones Gal-GlcNAc, alta manosilación y ácido siálico α2-3, en proteínas de vellosidad placentaria en los pesos moleculares encontrados, pudiera explicar cambios en la expresión de proteínas de membrana del STB.

Expression of human chorionic gonadotropin (ßhCG) in pre-eclamptic placenta / Expresión de gonadotropina coriónica humana (ßhCG) en placenta preeclámptica

This study aimed to assess association between preeclampsia with trophoblast cells and serum level of b-human chorionic gonadotropin (ß-hCG). Were compared 20 patients with preeclampsia and 20 control patients with respect to demographics, hematological parameters and the presence of trophopblast in placental samples. Patchy necrosis with loss of microvilli and gross thinning of the syncytium with distorted microvilli were seen in terminal villi of placentae of women with pre-eclampsia Syncytial cells at the molecular level crossings, especially at the level of ßhCG in conjunction with the changes in the preeclampsia was made on the histopathological changes to clarify the villi.

El objetivo fue evaluar la asociación entre la preeclampsia con células trofoblásticas y concentración sérica de la gonadotropina coriónica humana b (ß-hCG). Se compararon 20 pacientes con preeclampsia y 20 pacientes de control con respecto a datos demográficos, parámetros hematológicos y la presencia de trofoblasto en muestras de placenta. Se observaron áreas dispersadas de necrosis, con pérdida de microvellosidades y adelgazamiento del sincitio con microvellosidades distorsionadas en las vellosidades terminales de placentas en mujeres con células sincitiales preeclámticas a nivel molecular, junto a altos niveles de ßhCG asociados a los cambios generados por la preeclampsia sobre los parámetros histopatológicos.

Trofoblasto, impronta y conflicto genómico en gineco-obstetricia / Trophoblast, imprinting and genomic conflict in gynecology-obstetrics

La teoría del Conflicto Genómico es parte de la biología evolutiva y actúa en los mamíferos a través del mecanismo de impronta genética, estos genes cumplen un rol central en el desarrollo fetal y del trofoblasto contribuyendo a un balance entre los requerimientos nutricionales fetales (genes con impronta paterna) y el aporte materno (genes con impronta materna). El desbalance de estos genes tiene implicancias en la etiopatogenia de diversas patologías en Gineco-Obstetricia: en Medicina Fetal (preeclampsia, diabetes gestacional, síndrome de Beckwith-Wiedemann), oncología (mola completa, mola incompleta, teratomas) y fertilidad. Se presenta un caso de displasia mesenquimática placentaria asociado a Beckwith-Wiedemann.

The theory of Genomic Conflict is part of evolutionary biology and acts in mammals through the mechanism of genetic imprinting, these genes play a central role in fetal and trophoblastic development producing a balance between fetal nutritional requirements (genes with paternal imprinting) and maternal supply (genes with maternal imprinting). The imbalance of these genes has implications in the pathogenesis of various diseases in Obstetrics and Gynecology: in Fetal Medicine (preeclampsia, gestational diabetes, Beckwith-Wiedemann syndrome), oncology (complete and partial hydatiform mole, teratomas) and fertility. A case of placental mesenchymal dysplasia associated with Beckwith-Wiedemann is presented.

Morphological alterations in mouse placenta induced by diazepam / Alteraciones morfológicas inducidas en la placenta de ratón por diazepam

Diazepam (DZ) is a benzodiazepine that belongs to the group of minor tranquilizers with myo-relaxing and anticonvulsant properties. DZ and its metabolites cross the placental barrier in human, monkey, hamster, and mouse, and accumulate in the placenta. Our aim was to investigate, through histological techniques, and semifine sections if DZ induces morphological changes in the placenta. Twenty female mice of the ICR strain were distributed randomly in two groups. One group (DZ) was treated from days 6 to 17 of gestation with a single daily subcutaneous (sc) dose of DZ of 2.7 mg/kg/ (bw); the second, control group (C) was treated with saline solution. All females (10 DZ and 10 C) were killed by decapitation. Placentas were extracted and fixed in phosphates-buffered 10% formaldehyde, pH 7.3, dehydrated, and embedded in paraffin to obtain 3 µm thick sections or fixed in 2.5% glutaraldehyde, post-fixed in 1% OsO4, embedded in epoxy resin. Histological sections were stained with hematoxylin-eosin or Weigert´s iron hematoxylin. Semifine sections were stained with toluidine blue. All sections were observed under comparative light microscopy. The DZ-group showed thinned placental barrier with multiple vacuoles. Nuclei of trophoblast cells (TCs) and trophoblast giant cells (TGCs) presented heterochromatin in coarse granules, atypically distributed in the karyolymph and conspicuous nucleoli. The cytoplasm of the TGCs was vacuolated and chromatin had a similar appearance to that observed in TCs. The total area of the placental barrier was measured in µm2/µm2; the area in the DZ group was reduced as compared with the C group (P<0.001). Alterations of TGCs could be due to an interaction of DZ with peripheral type benzodiazepine receptors involved in progesterone biosynthesis. Administration of DZ in mice alters the placental barrier and TGCs which could affect their physiology and causes teratogenic effects on the ovary and testis involved in steroid hormones biosynthesis.

El diazepam (DZ) es una benzodiazepina que forma parte de los tranquilizantes menores con propiedades miorrelajantes y anticonvulsivantes. El DZ y sus metabolitos atraviesan la barrera placentaria en el humano, mono, hámster y ratón, y se acumula en ésta. Nuestro propósito fue investigar a través de técnicas histológicas y en cortes semifinos si el DZ induce cambios morfológicos en la placenta de ratón. Hembras de ratón de la cepa ICR se distribuyeron al azar en dos grupos. Un grupo (DZ) fue tratado del día 6 al 17 de la gestación con dosis únicas diarias subcutáneas (sc) de DZ de 2.7 mg/kg (pc); el segundo grupo control (C) se trató con solución salina. Todas las hembras (10 DZ y 10 C), se sacrificaron por decapitación. Se extrajeron las placentas y se fijaron en formaldehido al 10% amortiguado con fosfatos pH 7.3, se deshidrataron y se incluyeron en parafina para obtener cortes de 3 µm, o se fijaron en glutaraldehido al 2.5%, se posfijaron en OsO4 al 1% y se embebieron en resina epóxica. Los cortes histológicos se tiñeron con hematoxilina-eosina o con hematoxilina férrica de Weigert. Los cortes semifinos se tiñeron con azul de toluidina. Todos los cortes se observaron en un microscopio óptico de comparación. El grupo DZ presentó en la barrera placentaria múltiples vacuolas. Los núcleos de las células del trofoblasto y las células trofoblásticas gigantes (TGCs) presentaron heterocromatina en grumos gruesos, distribuidos atípicamente en la cariolinfa y nucléolos conspicuos. El citoplasma de las TGCs estaba vacuolizado y la cromatina tenía una apariencia similar a la observada en las células trofoblásticas. El área total de la barrera placentaria se midió en µm2/mm2; el área en el grupo DZ era reducida en comparación del grupo C (P<0.001). Las alteraciones de las células trofoblásticas y de las TGCs podrían deberse a la interacción del DZ con los receptores benzodiazepínicos de tipo periférico involucrados en la biosíntesis de progesterona. La administración de DZ en el ratón altera la barrera placentaria y las TGCs que podrían afectar su fisiología y causar efectos teratogénicos en el ovario y el testículo involucrados en la biosíntesis de las hormonas esteroides.

Mola hidatiforme completa y feto vivo a término coexistente: reporte de caso / Complete hydatidiform mole and alive fetus to term coexistent. case report

Se presenta el caso de una mola hidatiforme completa y feto vivo a término coexistente en una paciente de 30 años, II gestas I para, con embarazo de 29 semanas y elevación de la presión arterial. La imagen ecográfica al ingreso de la placenta sugirió la presencia de mola hidatiforme junto a un feto normal. Se realizó seguimiento expectante hasta las 37 semanas, cuando presentó un episodio de sangrado genital por lo que se realizó una cesárea y se obtuvo un recién nacido vivo masculino normal, placenta y una tumoración de un tejido vesicular. El examen de anatomía patológica del tejido vesicular reportó mola hidatiforme completa.

A case of complete hydatiform mole with live term coexisting fetus in a 30-year-old patient, II gravida, 1 para, with a pregnancy of 29 weeks and rise of blood pressure is presented. Ultrasound image at admission suggested the presence of hydatiform mole together a live fetus. Patient was followed until 37 weeks, when presented an episode of vaginal bleeding cause a cesarean section was done and a live normal male newborn, placenta and a vesicular tissue tumor were obtained. Pathology exam of vesicular tissue reported complete hydatiform mole.

Pré-eclâmpsia: o que há de anômalo na placentação? / Preeclampsia: what is wrong with placentation

A pré-eclâmpsia (PE) constitui a principal causa de morte materna em diversos países do mundo e contribui significativamente para a prematuridade, o baixo peso fetal e o aumento da mortalidade neonatal. A placenta constitui o substrato anatômico etiopatogênico principal para a doença, inclusive em ambiente extra-uterino ou na ausência de embrião. O único tratamento efetivo para a PE consiste na interrupção da gravidez e remoção completa da placenta. Em muitos casos, esta medida precisa ser tomada prematuramente, visando garantir a vida da mãe, do bebê ou de ambos. Estudos clínicos, histológicos e laboratoriais demonstram alterações hemodinâmicas, histológicas, imunológicas e bioquímicas na placentação de mulheres portadoras de PE. Entender como essas alterações assumem proporções sistêmicas no organismo materno pode ser a chave para impedir a progressão abrupta e violenta da doença. Certamente, o entendimento de todo o processo fisiopatológico é necessário para qualquer proposta de predição, prevenção ou terapia que possa diminuir as altíssimas taxas de mortalidade atribuídas à PE.

Preeclampsia (PE) is the leading cause of maternal death in many countries worldwide and contributes significantly to prematurity, low fetal weight and increased neonatal mortality. The placenta seems to be the main etiopathogenic anatomical substrate for the disease even in extra-uterine environment or in the absence of the embryo. The only effective treatment for PE is the pregnancy interruption and complete placenta removal. In many cases, this action needs to be taken prematurely in order to ensure the life of the mother, baby or both. Clinical, histological and laboratory have shown hemodynamic, histological, immunological and biochemical abnormalities in placentation in women with PE. Understanding how these changes take on systemic proportions in the mother may be the key to prevent the abrupt progression of the disease. Indeed, an understanding of all physiological and the alterations in PE process is required for any action of prediction, prevention or therapy that can reduce the extremely high rates of mortality associated to PE.