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Study of adenosine effects on proliferation of BeWo cell line
Papírník, Josef ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Josef Papírník Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Studium of adenosine on proiferation activity in BeWo cell line The placenta is a rapidly developing organ that provides nutrition, protection and environment for the growing fetus. Fetal development is dependent on the supply of nutrients from the mother's blood either by passive diffusion or mediated by transporters. One of the essential nutrients are nucleosides, which are known to promote DNA synthesis and thus the growth of certain tissues. In order to pass across the plasma membrane they need nukleoside transporters (NTs) because of its hydrophilic feature. Additionally Ado takes part in cell signaling. Its wide- ranging effects, including influencing proliferation, are mediated by its binding to adenosine receptors (ARs). The placenta expresses NTs and ARs, which means that it is equipped to uptake nucleosides from maternal blood and has ability to receive signals from the external environment via the adenosine molecule. However, the importance of nucleosides for placental growth has not been investigated yet. The aim of this thesis is to test the effect of nucleosides on the proliferation of...
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Study of adenosine effects on proliferation of JEG-3 cell line
Nguyen, Ngoc Duong ; Červený, Lukáš (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Nguyen Ngoc Duong Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Effect of adenosine on the proliferation of JEG-3 cell line Adenosine is a purinergic signaling molecule that is used in nucleic acid synthesis. Transport of hydrophilic nucleosides through the plasma and/or organelle membranes is provided by equilibrative nucleoside transporters (ENTs), members of the SLC29A transporter family, and concentrative nucleoside transporters (CNTs), members of the SLC28A transporter family. The placenta is a complex and rapidly growing organ. It shows some patterns similar to tumors except for the fact that the placenta's growth is fully controlled. It was found that extracellular nucleosides support the proliferation of cancerous and some non-cancerous cells. The placenta expresses high levels of NTs which indicates the placenta's ability to take up the nucleosides from circulation, however, the contribution of this process to placental growth is known. The diploma thesis aims to test the effect of adenosine and other nucleosides on trophoblast proliferation. We evaluated whether adenosine and other nucleosides increase the proliferation of the choriocarcinoma-derived JEG-3 cell...
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The effect of in vitro and ex vivo placental cells stimulation on expression of selected ABC and OATP transporters
Dudičová, Simona ; Čečková, Martina (advisor) ; Jirkovská, Anna (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Simona Dudičová Supervisor: Assoc. Prof. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: The effect of in vitro and ex vivo placental cells stimulation on expression of selected ABC and OATP transporters The placenta is an organ that plays a key role throughout pregnancy for proper fetal development. One of the important functions provided by the placenta is the transport of substances between the mother and the fetus. This transfer of substances enabled mainly by membrane transporters, which are located on the apical and basal membranes of the syncytiotrophoblast. During various physiological or pathological changes in the human body, their expression and amount can vary significantly. Inflammatory reactions that may occur during pregnancy are also related to these changes, and therefore we have addressed this issue and believed that this condition may alter the expression of placental transporters. The aim of this work was to investigate the changes in the expression of membrane transporters using placental cells on BeWo cell lines and placental villous explants that were stimulated by pro-inflammatory mediators. The change in the expression of individual ATP-binding cassettes,...
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Rhythmic function of placenta and the impact of disruption in maternal-placental-fetal axis
Světlíková, Nela ; Sumová, Alena (advisor) ; Pačesová, Dominika (referee)
In mammals, the circadian rhythms result of a complex endogenous system consisting of hierarchically organized oscillators. The system enables the synchronization of the organism's internal processes with the external environment. It consists of the main component, the central clock, located in the suprachiasmatic nuclei in the hypothalamus, and peripheral clocks in other cells, tissues and organs. The placenta is a temporary, specialized mammalian organ that is part of the mother-placenta-fetus axis and exhibits rhythmicity in its functions. The aim of this thesis is to summarize the rhythmic functions of the placenta, such as immunity, protection, and production of hormones and other mediators that play an important role in fetal development and pregnancy. In addition, the thesis also describes rhythmic changes, that occur during pregnancy in the mother-placenta-fetus axis and how these rhythms influence each other. Keywords Placenta, circadian clock, ontogenesis, fetus, maternal synchronization, hormones, enzymes, immunity
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Placental homeostasis of monoamines; effect of gestation age
Mahrla, Filip ; Štaud, František (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Filip Mahrla Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: PharmDr. Rona Karahoda, Ph.D. Title of diploma thesis: Placental homeostasis of monoamines; effect of gestation age Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence suggests their involvement in placental development and functions and a crucial role in fetal development and programming. Nonetheless, a comprehensive characterization of catecholamine synthesis, degradation, and transport in the fetoplacental unit is still lacking. Thus, in this thesis, we aimed to provide a comprehensive evaluation of catecholamine metabolism and transport in the fetoplacental unit. Gene and protein expression was evaluated using quantitative polymerase chain reaction (PCR) and Western blot analysis, respectively. Firstly, using several placental cell models (BeWo, JEG-3, primary trophoblast cells), we identified components of cellular catecholamine handling associated with the trophoblast cells. Next, we determined the effect of advancing gestation on the placental catecholamine system in humans (first trimester vs. term placenta) and...
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Changes in placental angiogenesis and their impact on fetal intrauterine growth restriction
Kudějová, Alena ; Švandová, Ivana (advisor) ; Magner, Martin (referee)
Any pathological interference with normal vascular development of placenta may have a critical impact on fetal growth and development. The proliferation and differentiation of several cell types play a very important role in the vascular system of placenta. The main factors taking part in the vascular development of placenta include cell elements (e.g. trofoblast, stromal chorion cells, haemangiogenic progenitors), the extracellular matrix, growth factors and cytokines (e.g. VEGF, PlGF, Ang-1,2 and bFGF). The extrinsic factors may also influence the partial oxygen pressure, nutritients availability, and/or the blood perfusion in placenta. Placental ischaemia leading to the worsening of uteroplacentar perfusion is the most common cause of the intrauterine growth retardation (IUGR). The IUGR development is then the result of insufficient prolongation, branching, and dilatation of capillary loops during the formation of terminal villi. Published studies focusing on growth factors in placentas from physiological pregnancies and pregnancies with IUGR do not give clear results. This BSc. Thesis is a review focused on up-to-date-known data concerning changes in placental angiogenesis and their impact on IUGR. Key words: placenta, angiogenesis, IUGR, pregnancy
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The influence of antidepressants on serotonin homeostasis in placenta
Váchalová, Veronika ; Štaud, František (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Veronika Váchalová Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: Mgr. Rona Karahoda Title of diploma thesis: The influence of antidepressants on serotonin homeostasis in placenta Depression is a serious mental disorder affecting 10-20% of women during pregnancy. Up to 10% of these pregnant women are prescribed antidepressants (ADs), most frequently from the class of selective serotonin (5-HT) reuptake inhibitors (SSRIs). While the safety of this treatment is questionable due to reported impaired pregnancy/fetal outcomes, understanding of potential mechanistic causes is still lacking. During pregnancy, 5-HT is important for normal placental function and proper fetal development and programming. 5-HT homeostasis in the placenta is maintained via the 5-HT transporter (SERT/SLC6A4) on the apical side and the recently characterized organic cation transporter 3 (OCT3/SLC22A3) on the basal side of trophoblast. These transporters take up 5-HT from the maternal and fetal circulations, respectively into the syncytiotrophoblast (STB) where it is degraded by monoamine oxidase-A (MAO-A). As all ADs interfere with the 5-HT system it is important to study their potential interactions in the...
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Study of interactions of antiviral drug tenofovir and its prodrug tenofovir disoproxil fumarate with placental nucleoside transporters
Lalinská, Anežka ; Červený, Lukáš (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anežka Lalinská Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Study of interactions of antiretroviral drug tenofovir and its prodrug tenofovir disoproxil fumarate with placental nucleoside transporters Tenofovir (TFV) in the form of ester prodrug tenofovir disoproxil fumarate (TDF) is an essential part of combination antiretroviral therapy. It is often used in the prevention of perinatal HIV transmission. However, precise mechanism(s) involved in transfer of TFV/TDF from mother to fetus are not described in detail. Since these drugs are nucleoside analogues, there is a possibility that the mechanisms of their transplacental passage might include nucleoside transporters (NTs), either equilibrative or concentrative (ENTs/CNTs). The aim of the diploma thesis was to investigate the role of placental NTs in membrane transfer of TFV and TDF. To address this issue, we performed in vitro accumulation in the BeWo cell line derived from placental choriocarcinoma. By evaluating experiments, we found out that both TFV and TDF might not be substrates of NTs, thus the role of these transporters in TFV/TDF placental pharmacokinetics was not confirmed. Therefore, the drug-drug interactions on NTs...
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Study of the effect of novel antiretroviral drugs on carnitine transport in the placenta
Marková, Eliška ; Čečková, Martina (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Eliška Marková Suprevisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Study of the effect of novel antiretroviral drugs on carnitine transport in the placenta Nowadays, the antiretroviral treatment of HIV-positive pregnant women is the standard approach for restriction of transmission of HIV infection from mother to the fetus. In spite of necessity of this pharmacotherapy, it is important to know its safety and risks. For the correct fetal development and function of placenta it is (besides others) essential to ensure the optimal supply of L-carnitine, the key factor for oxidation of fatty acids from mother's blood to the placenta and fetal blood circulation. The deficiency of L-carnitine generally leads to significant metabolic changes in the cells and in it usually demonstrated with cardiomyopathies and myopaties. Published studies indicate higher incidence of cardiovascular diseases and cardiomyopathies in children born to mothers treated with antiretroviral therapy during pregnancy. Optimal transport of carnitine into the placental cells, is ensured due to the presence of functional transport protein OCTN2 in the apical membrane of trophoblast. The aim of this study was...
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Study on expression of selected ABC transporters in placenta
Kučerová, Veronika ; Čečková, Martina (advisor) ; Karbanová, Sára (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Veronika Kučerová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Consultant: PharmDr. Lenka Ťupová, Ph.D. Title of diploma thesis: Study on expression of selected ABC transporters in placenta The placenta is a temporary organ through which the fetus is supplied with nutrients and oxygen from the mother's blood and conversely waste substances are transferred into the mother's blood during pregnancy. Substance transfer through the placenta is a complex process controlled by a number of physiological mechanisms, including passive diffusion, facilitated diffusion or active transport, which is realized by activity of membrane transporters with energy consumption. Presence of active ABCs efflux transporters in the placenta has been known for a long time and their function is associated primarily with limiting the entry of harmful substances into the placenta and further into the fetus, thus contributing to its protection. Among the best described transporters belong P-glycoprotein (MDR1/ABCB1), breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance protein 2 (MRP2/ABCC2), whose expression has been confirmed in the apical membrane of the placental syncitiotrophoblast facing...
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