Dokument: Mäuse mit reduzierter Expression von Syndecan-1: Reproduktion und Metabolismus
| Titel: | Mäuse mit reduzierter Expression von Syndecan-1: Reproduktion und Metabolismus | |||||||
| Weiterer Titel: | Mice with reduced expression of Syndecan-1: Reproduction and Metabolism | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=47613 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20181022-091717-9 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Gougoula, Christina [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. med. Bielfeld, Alexandra Petra [Gutachter] Prof. Dr. Lammert, Eckhard [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Maintenance of the energy balance is of outstanding importance for all species. It determines the dynamics between physiological processes such as reproduction and metabolism and can be an indicator of the organism’s health status. Circulating metabolic factors and neuroendocrine reproductive and metabolic indicators are modulated by secreted and cell-surface molecules such as the heparan sulfate proteoglycans. The uteroplacental localization of Sdc1 and its relation with pregnancy-associated pathologies like IUGR, preeclampsia and HELLP syndrome suggest an influence of Syndecan 1 (Sdc1) in embryo-maternal interactions and development of progenies. The aim of the present study was to investigate the reproductive and metabolic phenotype of the heterozygous Sdc1+/- mouse with regard to the growth restriction observed in human and mice as for ethical and practical reasons such research in human is impossible.
The results obtained with regard to the reduced body weight of the Sdc1+/- mice from the day of birth to the age of 6 months, as well as their increased death pace during the first postnatal days of life, either when they were carried by a Sdc1 female or by a wild type (WT) foster mother revealed a rather genotype- than environmental-related impaired reproduction and body weight development. A study on a Sdc1 overexpression mouse model intrigued us to investigate blood plasma levels of leptin, corticosterone, insulin and glucose in order to obtain information about the metabolic status in the case of Sdc1 deficiency, and to reveal a potential metabolic effect on its reproduction. Interestingly, Sdc1+/- mice had significantly increased leptin and decreased corticosterone levels. Insulin and glucose did not show any significant variations in comparison to WT animals. Subsequently, the purpose of the study was adjusted to answer the question in which degree reproduction and metabolism are connected and interdependent in the presence of Sdc1 deficiency. Leptin is a hormone basically produced by adipose tissue. We found that the Sdc1+/- mice showed less adipose tissue and also smaller adipocytes. Furthermore, despite their elevated leptin levels and reduced adipose tissue and in spite of their reduced weight, both male and female Sdc1+/- mice consumed more food per g body weight than the WT animals. Their increased energy expenditure could be the answer on their contradictory metabolic phenotype. Because of the fact that a body weight difference reflects also to organ weight fluctuations, various organs were examined. The kidneys of both male and female Sdc1+/- mice as well as of the females after the vice versa embryo transfers were found to be lighter than the WT ones. This was also the case for the testis of the Sdc1+/- male mice. As mentioned above the Sdc1+/- animals had also less adipose tissue. On the contrary, they presented heavier and longer full and empty intestines in proportion to their body weight. However, on the cellular level, the histological investigation of the intestinal villi and crypts did not reveal any significant differences between the Sdc1+/- and WT animals. Taken together, the present study revealed an influence of the Sdc1 reduction on the metabolic behavior of these mice, which further affected their reproduction, leading to mice with a growth restriction as observed in human and an impaired reproductive phenotype which reflects human pregnancy-associated pathologies. The results obtained could be describing a type of murine intrauterine growth restriction and/or a possible mouse preeclampsia. The question remains whether a clinical routinely detection of low levels of Sdc1 in human might be possible and an according supplementation could cure those pathologies. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 22.10.2018 | |||||||
| Dateien geändert am: | 22.10.2018 | |||||||
| Promotionsantrag am: | 26.07.2018 | |||||||
| Datum der Promotion: | 26.09.2018 |
