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16. Molecular characteristics of established trophoblast-derived cell lines

Author

Pastuschek, Jana, primary, Nonn, Olivia, additional, Gutiérrez-Samudio, Ruby N., additional, Murrieta-Coxca, Jose M., additional, Müller, Jasmin, additional, Sanft, Juliane, additional, Huppertz, Berthold, additional, Markert, Udo R., additional, Groten, Tanja, additional, and Morales-Prieto, Diana M., additional

Published
2021
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17. Fetal exposure to environmental chemicals; insights from placental perfusion studies

Author

Mathiesen, Line, Buerki-Thurnherr, Tina, Pastuschek, Jana, Aengenheister, Leonie, Knudsen, Lisbeth E., Mathiesen, Line, Buerki-Thurnherr, Tina, Pastuschek, Jana, Aengenheister, Leonie, and Knudsen, Lisbeth E.

Abstract

Introduction: The burden of environmental chemicals in the human population is ubiquitous and especially problematic in pregnancy due to potential exposure of the vulnerable fetus. According to the Developmental Origins of Health and Disease hypothesis, the fetal period is highly sensitive to exposure to environmental factors that will determine the development of diseases later in life. A range of environmental chemicals has been studied in the ex vivo placental perfusion model, which is a human model using the intact placenta directly after birth to study the placental transfer and metabolism of selected compounds. Methods: Here, we reviewed the existing knowledge on human placental perfusion of environmental chemicals in order to identify potential correlations between placental transfer and properties of chemicals and areas of future research needs. Results: We found 32 studies of the following groups of environmental chemicals: pesticides, persistent organic pollutants (POPs), plastics and byproducts, phyto/myco-estrogens and fungal toxins, byproducts from heating/curing food, combustion in traffic and industry, and metals. The studies showed highly distinct transfer rates from very fast transport to the fetal side to negligible transfer. Discussion: In general, a low molecular weight favors placental translocation, but placental translocation is dependent on other physicochemical properties of the substances, claiming the need for more standardized studies and proper quantitative structure-activity relationship (QSAR) analysis. Overall, we recommend using placental perfusion studies in the risk assessment of environmental toxicants, to determine the transfer, metabolism and toxic effects of this diverse class of substances, on the human term placenta.

Published
2021

19. Beyond Uterine Natural Killer Cell Numbers in Unexplained Recurrent Pregnancy Loss: Combined Analysis of CD45, CD56, CD16, CD57, and CD138

Author

Chiokadze, Maia, Bär, Christin, Pastuschek, Jana, Dons’koi, Boris V., Khazhylenko, Kseniia G., Schleußner, Ekkehard, Markert, Udo R., and Favaro, Rodolfo R.

Subjects
lcsh:R5-920, recurrent pregnancy loss, natural killer cells, hemic and immune systems, chemical and pharmacologic phenomena, Article, CD138, TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, embryonic structures, CD56, human, CD45, endometrium, lcsh:Medicine (General), CD57, CD16
Abstract

Changes in the number and cytotoxic potential of uterine Natural Killer (uNK) cells have been associated with reduced fertility. To provide a better characterization of immunophenotypes in the endometrium of women with uRPL (unexplained recurrent pregnancy loss), we examined the applicability of a set of five immune cell markers. The concentration (cells/mm2) of CD45+ leukocytes, CD56+ uNK cells, and CD138+ plasma cells as well as of CD16+ and CD57+ cells, which indicate high cytotoxic uNK cells, were assessed by immunohistochemistry in endometrial biopsies from 61 uRPL patients and 10 controls. Control fertile endometria presented 90&ndash, 300 CD56+ uNK cells/mm2. uRPL cases were classified in subgroups of low (uRPL-CD56low &lt, 90 cells/mm2), normal (uRPL-CD56normal 90&ndash, 300 cells/mm2), and high uNK cell counts (uRPL-CD56high &gt, 300 cells/mm2). Some cases from the uRPL-CD56low and uRPL-CD56normal subgroups showed elevated proportions of cytotoxic CD16+ and CD57+ cells in relation to CD56+ cells. In the uRPL-CD56high subgroup, the CD57/CD56 ratio was reduced in most samples and the CD16/CD56 ratio was unaltered. Analysis of CD138 excluded the influence of chronic endometritis on these observations. Our results reinforce a link between uRPL and a dysfunctional endometrial environment associated with distinct immune cell profiles.

Published
2020

21. Placental Histopathology in Risk Pregnancies

Author

Pastuschek Jana, Schleussner Ekkehard, Markert Udo R, Heimann Yvonne, Groten Tanja, and Brummer Clemens

Subjects
Pathology, medicine.medical_specialty, Reproductive Medicine, business.industry, Placental histopathology, Obstetrics and Gynecology, Medicine, business, Developmental Biology
Published
2021

22. Placenta inflammation, vaginal microbiome and Early-Onset Neonatal Sepsis (EONS) after Preterm Premature Rupture of Membranes (PPROM)

Author

Hiller G.G. Ruth, G.A. Borges Luiz, H. Pieper Dietmar, Zöllkau Janine, Dawczynski Kristin, Schleussner Ekkehard, Pastuschek Jana, and Heimann Yvonne

Subjects
medicine.medical_specialty, Neonatal sepsis, Obstetrics, business.industry, Obstetrics and Gynecology, Inflammation, medicine.disease, medicine.anatomical_structure, Reproductive Medicine, Placenta, medicine, Vaginal microbiome, medicine.symptom, business, Premature rupture of membranes, Developmental Biology, Early onset
Published
2021

24. Endometrial NK and plasma cells in infertile women

Author

Markert, Udo R., primary, Toth, Bettina, additional, Pastuschek, Jana, additional, Weber, Maja, additional, Bär, Christin, additional, Heger, Julia, additional, Streicher, Priska, additional, Schultz, Nora, additional, Kuon, Ruben, additional, Diao, Lianghui, additional, Donskoi, Boris, additional, Chiokadze, Maia, additional, Khazhylenko, Ksenia, additional, Santillán, Isabel, additional, Favaro, Rodolfo F., additional, and Schleußner, Ekkehard, additional

Published
2019
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33. Extracellular vesicles in blood, milk and body fluids of the female and male urogenital tract and with special regard to reproduction

Author

Foster, Brandon, Balassa, Timea, Benen, Thomas, Dominović, Marin, Elmadjian, Gabriel, Florova, Violetta, Fransolet, Maite, Kestlerova, Andrea, Kmiecik, Gabriela, Kostadinova, Irena, Kyvelidou, Christiana, Meggyes, Matyas, Mincheva, Mina, Moro, Laura, Pastuschek, Jana, Spoldi, Valentina, Wandernoth, Petra, Weber, Maja, Toth, Bettina, and Markert, Udo

Subjects
0301 basic medicine, Male, Amniotic fluid, Clinical Biochemistry, Uterus, Medizin, Urogenital System, exosomes, lactation, Biology, General Biochemistry, Genetics and Molecular Biology, Andrology, 03 medical and health sciences, blood, microparticles, microvesicles, ovary, platelets, pregnancy, semen, urine, uterus, Extracellular Vesicles, Pregnancy, Placenta, medicine, Humans, Lactation, Fetus, Blood Cells, Milk, Human, Genitourinary system, Biochemistry (medical), BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Trophoblast, Fetal Blood, Microvesicles, 030104 developmental biology, medicine.anatomical_structure, Cord blood, Immunology, Female, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti
Abstract

Extracellular vesicles (EVs) are released from almost all cells and tissues. They are able to transport substances (e.g. proteins, RNA or DNA) at higher concentrations than in their environment and may adhere in a receptor- controlled manner to specific cells or tissues in order to release their content into the respective target structure. Blood contains high concentrations of EVs mainly derived from platelets, and, at a smaller amount, from erythrocytes. The female and male reproductive tracts produce EVs which may be associated with fertility or infertility and are released into body fluids and mucosas of the urogenital organs. In this review, the currently relevant detection methods are presented and critically compared. During pregnancy, placenta-derived EVs are dynamically detectable in peripheral blood with changing profiles depending upon progress of pregnancy and different pregnancy- associated pathologies, such as preeclampsia. EVs offer novel non-invasive diagnostic tools which may reflect the situation of the placenta and the fetus. EVs in urine have the potential of reflecting urogenital diseases including cancers of the neighbouring organs. Several methods for detection, quantification and phenotyping of EVs have been established, which include electron microscopy, flow cytometry, ELISA-like methods, Western blotting, and analyses based on Brownian motion. This review article summarises the current knowledge about EVs in blood and cord blood, in the different compartments of the male and female reproductive tract, in trophoblast cells from normal and pre-eclamptic pregnancies, in placenta ex vivo perfusate, in the amniotic fluid, and in breast milk, as well as their potential effects on natural killer (NK) cells as possible targets

Published
2016

40. Oncostatin M and leukaemia inhibitory factor trigger signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 pathways but result in heterogeneous cellular responses in trophoblast cells

Author

Chaiwangyen, Wittaya, primary, Ospina-Prieto, Stephanie, additional, Morales-Prieto, Diana M., additional, Pereira de Sousa, Francisco Lazaro, additional, Pastuschek, Jana, additional, Fitzgerald, Justine S., additional, Schleussner, Ekkehard, additional, and Markert, Udo R., additional

Published
2016
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42. COV434 granulosa cell line: take it or leave it?

Author

Pastuschek, Jana, primary, Bus, Tanja, additional, Poetzsch, Jenny, additional, Raabe, Mariella, additional, Winkler, Simone, additional, Fritzsche, Andreas, additional, Schleussner, Ekkehard, additional, Markert, Udo R., additional, and Georgiev, Georgi, additional

Published
2014
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43. OncostatinMand leukaemia inhibitory factor trigger signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 pathways but result in heterogeneous cellular responses in trophoblast cells.

Author

Chaiwangyen, Wittaya, Ospina-Prieto, Stephanie, Morales-Prieto, Diana M., de Sousa, Francisco Lazaro Pereira, Pastuschek, Jana, Fitzgerald, Justine S., Schleussner, Ekkehard, and Markert, Udo R.

Subjects
ONCOSTATIN M, MULTIDRUG resistance, CYTOKINES, TROPHOBLAST, STAT proteins
Abstract

Leukaemia inhibitory factor (LIF) and oncostatin M (OSM) are pleiotropic cytokines present at the implantation site that are important for the normal development of human pregnancy. These cytokines share the cell membrane receptor subunit gp130, resulting in similar functions. The aim of this study was to compare the response to LIF and OSM in several trophoblast models with particular regard to intracellular mechanisms and invasion. Four trophoblast cell lines with different characteristics were used: HTR-8/SVneo, JEG-3, ACH-3P and AC1-M59 cells. Cells were incubated with LIF, OSM (both at 10 ngmL-1) and the signal transducer and activator of transcription (STAT) 3 inhibitor S3I-201 (200 mM). Expression and phosphorylation of STAT3 (tyr705) and extracellular regulated kinase (ERK) 1/2 (thr202/204) and the STAT3 DNA-binding capacity were analysed by Western blotting and DNA-binding assays, respectively. Cell viability and invasiveness were assessed by the methylthiazole tetrazolium salt (MTS) and Matrigel assays. Enzymatic activity of matrix metalloproteinase (MMP)-2 and MMP-9 was investigated by zymography. OSM and LIF triggered phosphorylation of STAT3 and ERK1/2, followed by a significant increase in STAT3 DNA-binding activity in all tested cell lines. Stimulation with LIF but not OSM significantly enhanced invasion of ACH-3P and JEG-3 cells, but not HTR-8/SVneo or AC1-M59 cells. Similarly, STAT3 inhibition significantly decreased the invasiveness of only ACH- 3P and JEG-3 cells concomitant with decreases in secreted MMP-2 and MMP-9. OSM shares with LIF the capacity to activate ERK1/2 and STAT3 pathways in all cell lines tested, but their resulting effects are dependent on cell type. This suggests that LIF and OSM may partially substitute for each other in case of deficiencies or therapeutic interventions. [ABSTRACT FROM AUTHOR]

Published
2016
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44. STAT5 is Activated by Epidermal Growth Factor and Induces Proliferation and Invasion in Trophoblastic Cells.

Author

Ospina-Prieto, Stephanie, Chaiwangyen, Wittaya, Pastuschek, Jana, Schleussner, Ekkehard, Markert, Udo R., and Morales-Prieto, Diana M.

Subjects
TROPHOBLAST, STAT proteins, EPIDERMAL growth factor, EMBRYO implantation, CELL cycle, PREGNANCY complications, MESSENGER RNA
Abstract

Epidermal growth factor (EGF) is expressed by decidual and trophoblast cells and influences manifold cellular functions during embryo implantation. Thus far, signaling of EGF via Signal Transducer and Activator of Transcription 5 (STAT5) has been only partially investigated. STAT5 stimulates proliferation and cell cycle progression in several cell types. Its dysregulation is associated with pregnancy. The aim of this study was to investigate STAT5 activation and function mediated by EGF in 2 trophoblastic cell lines, namely, HTR8/SVneo and JAR. Additionally, expression of STAT5B messenger RNA (mRNA) in trophoblast models has been compared to that of primary cells isolated from term placentas. Our results demonstrate the highest STAT5B mRNA expression in isolated trophoblast cells, lower expression in HTR8/SVneo cells, and the significantly lowest in JAR cells. Moreover, EGF-mediated STAT5 activation increases cell proliferation and viability in both cell lines. The STAT5 knockdown results in significant decrease in cell viability induced by EGF. Only in HTR8/SVneo cells, invasion decreases after STAT5 silencing and this effect cannot be rescued by further addition of EGF. These results demonstrate that STAT5 activated by EGF constitutes an important cascade for the regulation of cell proliferation and invasion in trophoblast cells. [ABSTRACT FROM AUTHOR]

Published
2015
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45. Cytokines Regulating Trophoblast Invasion

Author

Fitzgerald, Justine S., primary, Abad, Cilia, additional, Alvarez, Angela M., additional, Mehta, Ratnesh Bhai, additional, Chaiwangyen, Wittaya, additional, Dubinsky, Valeria, additional, Silva, Barbara Gueuvoghlanian, additional, Gutierrez, Gabriela, additional, Hofmann, Simone, additional, Hölters, Sebastian, additional, Joukadar, Jennifer, additional, Junovich, Gisela, additional, Kuhn, Christina, additional, Morales-Prieto, Diana M., additional, Nevers, Tania, additional, Ospina-Prieto, Stephanie, additional, Pastuschek, Jana, additional, Pereira De Sousa, F. Lazaro, additional, San Martin, Sebastian, additional, Suman, Pankaj, additional, Weber, Maja, additional, and Markert, Udo R., additional

Published
2011
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