Trophoblasts
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INTRODUCTION: Placental oxidative stress has been implicated in pregnancy complications and previous work has shown that selenium can protect trophoblast mitochondria from oxidative stress. This report examines mitochondrial function and content in trophoblasts supplemented with selenium. METHODS: Swan-71, JEG-3 and BeWo cells and placental tissue were incubated with sodium selenite or selenomethionine. Mitochondrial function was examined in a respirometer. Mitochondrial content was determined using RT-PCR. The levels of the mitochondrial biogenesis markers selenoprotein H, PGC-1α and NRF-1 was examined by western blotting. RESULTS: Mitochondrial respiration was significantly enhanced post selenium supplementation in cells and tissues. Selenium supplementation increased mitochondrial content and up-regulated mitochondrial biogenesis mediators in cells. DISCUSSION: These results emphasise the importance of selenium in mitochondrial regeneration in trophoblasts.
- MeSH
- biogeneze organel * MeSH
- buněčné linie MeSH
- DNA vazebné proteiny metabolismus MeSH
- faktor 1 související s NF-E2 metabolismus MeSH
- lidé MeSH
- mitochondrie účinky léků metabolismus MeSH
- placenta účinky léků metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- selen aplikace a dávkování MeSH
- selenoproteiny metabolismus MeSH
- těhotenství MeSH
- transkripční faktory metabolismus MeSH
- trofoblasty účinky léků metabolismus MeSH
- upregulace účinky léků MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In a cell-based non-invasive prenatal test (cbNIPT), intact circulating trophoblasts (CTs) are isolated from maternal blood for subsequent genetic analysis. Enrichment of these CTs from maternal blood is the most challenging step in the cbNIPT workflow. This study aims to assess the suitability of the filtration-based Metacell® technology to enrich CTs from maternal blood at week 10 to 13 of gestation. The Metacell® technology is a novel size-based enrichment technology that combines blood filtration through 8 μm pores with an in vitro culture method. Three protocols were evaluated. First, 8 mL or 16 mL of maternal blood was filtered and subsequently cultured in vitro on the separation membrane for 3 days in RPMI 1640. In addition, 16 mL of maternal blood was filtered, and immediately processed without further culturing. Y-chromosome-specific qPCR or STR analysis was performed to evaluate the enrichment of CTs. A total of 44 samples from pregnant women, out of which 26 were carrying a male fetus, were processed. Although five enriched male fetus samples show detectable male DNA quantities, it cannot be excluded that the obtained positive signal is caused by cell-free fetal DNA sticking to the Metacell® separation membrane. In conclusion, the Metacell® technology, tested as described, is not suitable for consistent enrichment of CTs.
- MeSH
- DNA MeSH
- lidé MeSH
- plod MeSH
- prenatální diagnóza * metody MeSH
- technologie MeSH
- těhotenství MeSH
- trofoblasty * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Three primary monoamines-serotonin, norepinephrine, and dopamine-play major roles in the placenta-fetal brain axis. Analogously to the brain, the placenta has transport mechanisms that actively take up these monoamines into trophoblast cells. These transporters are known to play important roles in the differentiated syncytiotrophoblast layer, but their status and activities in the undifferentiated, progenitor cytotrophoblast cells are not well understood. Thus, we have explored the cellular handling and regulation of monoamine transporters during the phenotypic transitioning of cytotrophoblasts along the villous pathway. METHODS: Experiments were conducted with two cellular models of syncytium development: primary trophoblast cells isolated from the human term placenta (PHT), and the choriocarcinoma-derived BeWo cell line. The gene and protein expression of membrane transporters for serotonin (SERT), norepinephrine (NET), dopamine (DAT), and organic cation transporter 3 (OCT3) was determined by quantitative PCR and Western blot analysis, respectively. Subsequently, the effect of trophoblast differentiation on transporter activity was analyzed by monoamine uptake into cells. RESULTS: We present multiple lines of evidence of changes in the transcriptional and functional regulation of monoamine transporters associated with trophoblast differentiation. These include enhancement of SERT and DAT gene and protein expression in BeWo cells. On the other hand, in PHT cells we report negative modulation of SERT, NET, and OCT3 protein expression. We show that OCT3 is the dominant monoamine transporter in PHT cells, and its main functional impact is on serotonin uptake, while passive transport strongly contributes to norepinephrine and dopamine uptake. Further, we show that a wide range of selective serotonin reuptake inhibitors affect serotonin cellular accumulation, at pharmacologically relevant drug concentrations, via their action on both OCT3 and SERT. Finally, we demonstrate that BeWo cells do not well reflect the molecular mechanisms and properties of healthy human trophoblast cells. CONCLUSIONS: Collectively, our findings provide insights into the regulation of monoamine transport during trophoblast differentiation and present important considerations regarding appropriate in vitro models for studying monoamine regulation in the placenta.
The authors suhmit an analysis of the clinical pathological material of the nationwide trophoblastic diseases centre (CTN) from 1955-1996. It comprises a total of 5 735 cases of trophoblastic disease (TN). This comprises choriocarcinoma (CH) 343 times, so far the largest group of CH verified by histological examination. It comprises furthermore proliferating mole (MP) 202 times complete hydatid mole (MHK) 360 times, partial hydatid mole (MHP) 1150 times persisting trophoblastic invasion (PTI) < 330 times, trophoblastic invasion (TI) 3 220 times and persisting trophoblastic disease (PTN) 130 times. The author presents the morphological classification and diagnosis of TN proposed and used in CTN on a nationwide scale. It assessest the importance of different types of TN for their treatment and prognosis. The following units are defined: 1. Trophoblastic invasion, 2. Persisting trophoblastic invasion 3. Partial hydatid rnole, 4. Complete hydatid mole, 5. Proliferating mole, 6. Choriocarcinoma which comprises five different types. In trophoblastic invasion the author describes its histological and cytological variability which formerly accounted for as much as 50% false positive diagnoses. Nowadays it is doubtful only in 5%. Persisting trophoblastic invasion was defined in CTN as a new special pathological unit of TN. Usually it recedes spontaneously. Nevertheless in 3% it was in CTN an indication for chemotherapy. In partial hydatid mole and in complete hydatid mole the morphological signs were, defined, which make their differential diagnosis possible which is essential for assessment of their prognosis. After complete hydatid mole choriocarcinoma developed in CTN in 6%. After partial hydatid mole the development of choriocarcinoma was not observed so far in CTN. Proliferating mole is defined in CTN in histological terms which makes its diagnosis from curettage possible. A malignant reversal of proliferating mole was recorded in CTN in 10%. Chemotherapy of proliferating mole was essential in 15%. The mortality rate of choriocarcinoma after proliferating mole declined from the original 85% to 3% and was zero during the last 10 years. According to the CTN classification there are five types of choriocarcinoma which differ markedly as to their biological properties and response to chemotherapy. The histological types of choriocarcinoma were defined on the basis of correlation with orthological trophoblasts of 7 to 20-day-old embryos. The types are: 1. Differentiated syncytiotrophoblastic choriocarcinoma, 2. Mixed differentiated choriocarcinoma, 3. Differentiated cytotrophoblastic choriocarcinoma, 4. Non-differentiated choriocarcinoma, 5. Dissociated choriocarcinoma. Types 1 and 2 respond excellently to chemotherapy and produce high values of hCG. Type 3, 4 and 5 are not very sensitive to chemotherapy or even resistant and produce low values of hCG. Some require primary surgery. They are histologically defined forms of so-called Placental Site Trophoblastic Tumours.
- MeSH
- lidé MeSH
- mola hydatidosa patologie MeSH
- trofoblastické nádory diagnóza patologie terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
Súhrn: Ľudská placenta predstavuje životne dôležitú bariéru medzi matkou a vyvíjajúcim sa plodom počas tehotenstva. Porucha včasného vývoja placenty je spojená so závažnými poruchami tehotenstva. Napriek jej komplexnému vývoju stále nie sú úplne objasnené rôzne molekulárne procesy riadiace vývoj placenty a špecializáciu buniek trofoblastu. Jednou z hlavných prekážok je nedostatok vhodných bunkových modelových systémov. Tradičné dvojrozmerné (2D) bunkové kultúry nedokážu imitovať podmienky in vivo a nezachytávajú zložité medzibunkové interakcie nevyhnutné na štúdium vývoja placenty. Avšak trojrozmerné (3D) modely organoidov, odvodené z kmeňových buniek, ktoré replikujú prirodzenú organizáciu a architektúru buniek výrazne zlepšili naše chápanie správania sa trofoblastov a ich medicínskych aplikácií. Organoidy s relevantnými fenotypmi poskytujú cennú platformu na modelovanie fyziológie a patológie placenty, vrátane modelovania porúch placenty. Sú veľkým prísľubom pre personalizovanú medicínu, zlepšenie diagnostiky a hodnotenia účinnosti a bezpečnosti farmaceutických liečiv. Tento článok poskytuje stručný prehľad trofoblastových kmeňových buniek, invázie trofoblastu a rozvíjajúcej sa úlohy organoidov v gynekológii.
The human placenta serves as a vital barrier between the mother and the developing fetus during pregnancy. A defect in the early development of the placenta is associated with severe pregnancy disorders. Despite its complex development, various molecular processes control placental development, and the specialization of trophoblast cells is still not fully understood. One primary obstacle is the lack of suitable cell model systems. Traditional two-dimensional (2D) cell cultures fail to mimic in vivo conditions and do not capture the intricate intercellular interactions vital for studying placental development. However, three-dimensional (3D) organoid models derived from stem cells that replicate natural cell organization and architecture have greatly improved our understanding of trophoblast behavior and its medicinal applications. Organoids with relevant phenotypes provide a valuable platform to model both placental physiology and pathology, including the modeling of placental disorders. They hold great promise for personalized medicine, improved diagnostics, and the evaluation of pharmaceutical drug efficacy and safety. This article provides a concise overview of trophoblast stem cells, trophoblast invasion, and the evolving role of organoids in gynecology.
- MeSH
- kmenové buňky fyziologie MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- organoidy fyziologie MeSH
- placenta * cytologie patologie MeSH
- těhotenství MeSH
- trofoblasty fyziologie MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
The placenta is the first organ to be created during mammalian development. As the main link between the mother and the fetus it has more diverse functions than any other organ, serving as a digestive, excretory, respiratory, endocrine, and immune system. The outer layer of the placenta, the trophoblast, plays a key role in fetal development by orchestrating all these functions. Recent research has associated perturbations of maternal conditions (such as malnutrition, stress or inflammation) with alterations of the trophoblasts' endocrine, transport and metabolic processes. As reviewed here, adaptations to these conditions enable the fetus to survive, but at the cost of permanently changing its physiology and structure. Moreover, these adaptations trigger fetal programming that increases predisposition to various pathological conditions in adult life, typically metabolic, cardiovascular or CNS diseases.
- MeSH
- biologické modely MeSH
- lidé MeSH
- maternofetální výměna látek účinky léků fyziologie MeSH
- placenta fyziologie MeSH
- těhotenství MeSH
- trofoblasty cytologie účinky léků fyziologie MeSH
- vývoj plodu účinky léků fyziologie MeSH
- xenobiotika toxicita MeSH
- zpožděný efekt prenatální expozice etiologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Clinical obstetrics and gynecology, ISSN 0009-9201 vol. 46, no. 3, September 2003
ix, 511-746 s. : il., tab., grafy ; 26 cm
