Résumé
Animal models are essential to understand healthy human placentation. Guinea pig related rodents became on focus for such purposes. In particular, processes of trophoblast invasion are similar. The latter is associated with a specialized area, the subplacenta. Since previous results showed differences between the guinea pig and its close relative Galea spixii, we aimed to study subplacental development with more detail. We investigated 16 pregnant females of 14 to 55 days of gestation by means of histology, morphometrics, immunohistochemistry and electron microscopy. The overlap between the fetomaternal blood systems resulted as intimate, suggesting some exchange processes. Proliferation was revealed by three independent methods, being most active in early and mid-gestation, which was in accordance to former results. Though degeneration of tissues took place, the subplacenta was maintained towards term with access to the fetal vascularization, supporting a hypothesis about the release of substances to the fetal unit in advanced gestation. In contrast to other species, the extraplacental trophoblast showed a shift from syncytial streamers to giant cells during mid-gestation. Views on placentation in caviomorphs were influenced by the guinea pig, but our data supported recent studies that the subplacenta had a much greater placidity. In regard to subplacental grow, degeneration and likely also exchange processes, Galea and other species showed a more basal pattern of caviomorphs than the guinea pig. Such differences should be considered, when choosing most adequate animal models for special purposes in comparison to human placentation.(AU)
Modelos animais são essenciais para entender a placenta humana sadia. Neste sentido os roedores relacionados ao porquinho da índia tornaram-se foco para tal entendimento. Em particular, os processos de invasão trofoblástica são semelhantes. O último está associado a uma área especializada, a subplacenta. Uma vez que os resultados anteriores mostraram diferenças entre o porquinho da índia e seu relativo o preá, buscamos estudar o desenvolvimento subplacentário com mais detalhes. Pesquisamos 16 fêmeas gestantes de 14 a 55 dias de gestação por meio de histologia, morfometria, imuno-histoquímica e microscopia eletrônica. A sobreposição entre os sistemas sanguíneos materno e fetal apresentou-se com íntima relação, sugerindo alguns processos de troca. A proliferação foi revelada por três métodos independentes, sendo mais ativos no início e metade da gestação, o que corroborou com os resultados anteriores. Embora a degeneração dos tecidos tenha ocorrido, a subplacenta foi mantida até o termo gestacional com acesso à vascularização fetal, apoiando uma hipótese sobre a liberação de substâncias para a unidade fetal em gestação avançada. Em contraste com outras espécies, o trofoblasto extraplacentário mostrou uma mudança de flâmulas sinciciais para células gigantes durante a metade da gestação. As visualizações sobre a placentação em caviomorfos foram influenciadas pelo porquinho da índia, mas nossos dados apoiaram estudos recentes de que a subplacenta apresentava uma plasticidade muito maior. Em relação ao crescimento subplacentário, a degeneração e provavelmente também os processos de troca, o preá e outras espécies apresentaram um padrão mais basal de caviomorfos do que o porquinho da índia. Tais diferenças devem ser consideradas, ao escolher os modelos animais mais adequados para fins especiais em comparação com a placentação humana.(AU)
Sujets)
Animaux , Femelle , Grossesse , Cochons d'Inde , Placenta/anatomie et histologie , Placentation/physiologie , Modèles animaux , Cochons d'Inde/anatomie et histologieRésumé
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.
Sujets)
Humains , Femelle , Grossesse , Sous-unité bêta de la gonadotrophine chorionique humaine/sang , Pré-éclampsie/sang , Pré-éclampsie/anatomopathologie , Trophoblastes , Immunohistochimie , NécroseRésumé
Placenta is an association of fetal and maternal tissues which develops during pregnancy. Placenta is often called lifeline, because it is the link between mother and growing fetus. It serves variety of functions, which include transport of nutrients to growing fetus, waste products from fetus, exchange of gases and also immunological protection to the fetus. It has a unique ability to function as a hypothalamo-pituitary-gonadal-axis as it can produce a variety of peptide, protein and steroid hormones. Thus, it is an autonomous unit capable of regulating its own growth and function.
Résumé
When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with Km of 168 microM and 371 microM in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [3H]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [3H]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.
Sujets)
Animaux , Femelle , Humains , Grossesse , Rats , Anions , Région mammaire , Lignée cellulaire , Ciclosporine , Traitement médicamenteux , Foetus , Tumeurs de l'ovaire , Glycoprotéine P , Paclitaxel , Placenta , Femmes enceintes , ARN messager , Trophoblastes , VérapamilRésumé
When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with Km of 168 microM and 371 microM in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [3H]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [3H]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.
Sujets)
Animaux , Femelle , Humains , Grossesse , Rats , Anions , Région mammaire , Lignée cellulaire , Ciclosporine , Traitement médicamenteux , Foetus , Tumeurs de l'ovaire , Glycoprotéine P , Paclitaxel , Placenta , Femmes enceintes , ARN messager , Trophoblastes , VérapamilRésumé
Objective To study the relationship between syncytiotrophoblast microvillous membrane (STBM) shedding in severe preeclampsia (sPE) and placenta Rho/ROCK molecule expression. Methods In this study, placenta tissue of 20 sPE lying-in women (sPE group) and 20 normal lying-in women (control group) were collected. The syncytiotrophoblast microvillous structure of the placenta tissue was scrutinized with transmission electron microscope (TEM). The microvillous numerical density (Nv), surface density (Sv), and volume density (Vv) of the cell surfaces were analyzed with stereology method. Western blotting and immunohistochemistry were used to detect the expression of Rho subfamily proteins (RhoA, RhoB, RhoC) and Rho kinases (ROCKI, ROCKII) in the placenta tissues. The correlation of the expression of Rho, ROCK proteins, and the shedding of STBM was examined with Spearman rank correlation analysis. Results The Nv, Sv, and Vv of the syncytiotrophoblast microvillous membranes in sPE group were significantly less than those of the control group (P<0.05). Compared with the control group, the expression levels of RhoA, RhoB, ROCKI, and ROCKII proteins in sPE group were noticeably elevated (P<0.05). In sPE group, the expressions of RhoB, ROCKI, and ROCKII proteins were positively correlated with the shedding of STBM (r=0.631, r=0.826, r=0.865, P<0.05). Conclusion The signaling pathways constituted by RhoB and its downstream molecules ROCKI/ROCKII, may play an important regulatory role in the upregulation of STBM shedding in sPE.
Résumé
Objetivo: El presente estudio analiza el efecto de diferentes retinoides sobre la función y diferenciación celular del trofoblasto humano en cultivo. Material y métodos: Se realizó un estudio experimental in vitro, en donde se utilizaron vellosidades coriónicas y células de citotrofoblasto obtenidas de placentas de término de embarazos normales, que fueron cultivadas y estimuladas con concentraciones fisiológicas diferenciales de retinol (ROL), ácido 9-cis retinoico (CRET) y ácido all-trans retinoico (TRET). Se analizaron los cambios en la actividad de la metaloproteinasa-9 (MMP-9) y la metaloproteinasa-2 (MMP-2), además de documentar las condiciones óptimas para el cultivo. En una segunda fase, se estimularon células de citotrofoblasto (CTB) aisladas y se documentaron los cambios morfológicos de formación de sincicio in vitro al ser estimulados con los retinoides mencionados. Resultados: Los explantes de placenta respondieron en forma dosis dependiente, en la actividad de MMP-2 y MMP-9 cuando fueron incubados en presencia de ROL y en menor proporción cuando se incubaron con CRET y TRET. El CTB aislado y estimulado con ROL y CRET formó sincicio en un lapso de 48 horas, en tanto que los estimulados con TRET lo hicieron hasta el 4o. día de incubación. Conclusiones: La placenta y el trofoblasto aislado responden a los diferentes retinoides. La respuesta del CTB al ROL indica que el CTB cuenta con la maquinaria metabólica para transformar el retinol en CRET y TRET que tienen actividad biológica. El efecto de estos compuestos se pudiera expresar en la función de implantación y en la placenta en desarrollo.
Objective: In the current study we investigate the effect of different retinoids on the function and cellular differentiation of human cytotrophoblast (CTB) cells in culture. Material and Methods: Experimental in vitro study that analyzed explants of placenta from term pregnancy were cultured and stimulated with different physiological concentrations of retinol (ROL), 9-cis retinoic acid (CRET) and all-trans retinoic acid (TRET). The optimal conditions of CTB culture and changes in metalloproteinase-9 (MMP9) and metalloproteinase-2 (MMP2) secretion stimulated by retinoids were analyzed by zymography. Isolated CTB cells were stimulated with retinoids and morphological changes of in vitro syncytio formation were observed by light microscopy. Results: The explants of placenta had a dose-dependent increment in the activity of MMP-2 and MMP-9 when they were incubated in presence of ROL and in less proportion when they were incubated with CRET and TRET. For isolated CTB cells, CRET stimulates the differentiation to syncytio within 48 h of incubation, whereas in the absence of TRET differentiation started after the fourth day incubation. Conclusions: The placenta and isolated CTB cells have the capacity to respond to ROL, this fact suggest the presence of a metabolic pathway necessary to transform retinol to the biological active retinoids like CRET and TRET. The effect of these retinoids might be expressed in the function of implantation and developing placenta.
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Objective: To investigate the effect of HCV persistent infection on biological behavior of human placental syncytiotrophoblast in vitro. Methods: Using Matrigel invasion assay,cell adhesive assay and migration assay to measure the effect of HCV persistent infection on invasive and relative adhesive and migration ability of human placental syncytiotrophoblast in vitro.Content of HCG in supernatant of the cultured medium was detected to evaluate the change of hormone synthesis and secretion of the infected syncytiotrophoblast.Results: Ability of invasion,adhesion,migration and function of hormone synthesis and secretion of infected syncytiotrophoblast decreased significantly in comparison with cells of control group(P
Résumé
No abstract available.