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Studies towards biological function of ubiquitin E3 ligase Rnf121 in vivo and in vitro
Škarabellová, Kateřina ; Sedláček, Radislav (advisor) ; Čermák, Lukáš (referee)
Although the RING finger protein 121 (RNF121) is a highly conserved E3 ubiquitin ligase from Caenorhabditis elegans to human, its function is poorly understood and in higher eukaryotes it has been studied only at in vitro level. RNF121 has been described to have various functions: i) it was ascribed to function as a broad regulator of NF-κB activation, ii) it was shown to control intracellular trafficking of various membrane proteins, and iii) its downregulation leads to apoptosis. Moreover, RNF121 might have a role in cancer as its expression was found to be 16.4-fold higher in patients suffering from Barrett esophagus (precancerous lesion of esophageal adenocarcinoma) and was even more increased in esophageal adenocarcinoma comparing to healthy population. In addition, RNF121 gene is localized in the candidate region containing breast cancer susceptibility genes. To gain insight into physiological functions of RNF121, Rnf121 knockout mice (Rnf121tm1b(EUCOMM)Hmgu ) were generated in the Czech Centre for Phenogenomics and further studied in our laboratory. Rnf121+ /- intercross breedings showed a prenatal lethal phenotype of Rnf121-/- embryos, which were dying prior embryonic day (E) 11.5. Preliminary experiments carried out in our laboratory showed numerous vascular defects in null mutant embryo,...
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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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Prenatal stress in the farm animals
Tylová, Barbora ; Chaloupková, Helena (advisor) ; Hradec, Michal (referee)
This bachelor thesis presents summary information about prenatal stress in farm animals, more precisely in ruminants. The thesis is based on scientific papers and literature. Prenatal stress is divided according to stressors that can affect animals in agriculture like transport, manipulation, diet restriction, isolation, social instability and heat stress. The work describes principles of how the stress is transmitted from mother to the fetus, how the stress affects them and to what extent. Scientific articles confirmed the effect of prenatal stress on placental development (Baxter et al., 2016 ; McCrabb and Bortolussi, 1997) birth weight (Roussel et al., 2004; Duuvaux Ponter et al., 2003) nervous system (Weinstock, 2001; Baxter et al. 2016) and the offspring behavior (Roussel Huchette et al., 2008; Laporte Broux et al., 2012; Coulon et al., 2011). As pregnant females were in most of the cases exposed to a mild stress (compared to previous experiments on laboratory animals) the effect on offspring had a little impact on the body that proved to be beneficial. Some studies showed that abnormalities that were measured after birth were not proven at later age.
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