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Rab proteins in sperm life
Vojtová, Kristýna ; Páleníková, Veronika (advisor) ; Zelenková, Natálie (referee)
Rab proteins are the largest group of small GTPases. They work as key regulators in the intracellular vesicular transport of cells. This bachelor's thesis contains a literature review of current information on the function of Rab proteins in mammalian spermatozoa. The first part of the work is devoted to their structure, function, cycle, and diseases related to the dysfunction of Rab proteins. The second part is focused on sperm development and maturation linked with specific Rab proteins involved in individual steps during the life of the sperm. Rab proteins are important in cytoskeletal organization and cytokinesis of sperm during spermatogenesis. They participate in the acrosome biogenesis mediated by the Golgi apparatus and the morphological changes of sperm during spermiogenesis. They also play a key role in the acrosome reaction and interaction with the zona pellucida. Due to their necessity in the sperm development and maturation, Rab proteins are proposed as a marker of male fertility, which is summarized in the last part of the thesis. Keywords Rab proteins, GTPases, sperm, spermatogenesis, spermiogenesis, fertilization, infertility
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The role of centrobin in spermatogenesis
Flintová, Jennifer ; Komrsková, Kateřina (advisor) ; Šebková, Nataša (referee)
Spermatogenesis is a highly orchestrated, strictly regulated cascade of events that could be divided into three major processes: mitotic expansion of diploid germ cells (spermatocytogenesis), meiotic division creating haploid cells, and spermiogenesis. Spermiogenesis, the final stage of spermatogenesis comprises a striking metamorphosis of round haploid spermatids into morphologically and functionally specialized spermatozoa designed for the fertilization. One of the proteins indispensable for proper sperm morphogenesis is centrobin, a structural component of the specialized cytoskeletal structures of the elongating spermatids (acroplaxome and manchette), executing essential role in sperm head shaping and assembly of the head-tail coupling apparatus. Disruption in Cntrob gene (coding for centrobin) in rats homozygous at the hd (hypodactyly) locus results in male infertility, with a striking morphological signature called "decapitated sperm syndrome" with detachment of sperm head from the flagellum due to impaired head-tail coupling. However, molecular function of centrobin in spermiogenesis is still unknown. Sperm decapitation is a distinct phenotype described in several mouse mutants and importantly from infertile human males. Strikingly, in addition to proteins functioning in cytoskeletal...
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Targeted next generation sequencing of candidate genes responsible for impaired spermatogenesis and male infertility
Daňková, Michaela ; Liška, František (advisor) ; Holá, Dana (referee)
Infertility is a widespread health problem, caused by the male factor in about half of all cases, and in about a half of the infertile men the cause is unknown. In a significant number of these men, genetic etiology is assumed. Current routine methods of laboratory diagnostics, which include karyotype examination, exclusion of mutations in the CFTR gene, and Y chromosome microdeletions, do not usually reveal the cause of infertility. That is why researchers' efforts aim at detecting mutations in other genes that are causing male infertility. In recent years, animal models have been used to identify many genes necessary for fertility. Based on these findings, 12 candidate genes have been selected (CAPZA3, CDC14B, CDC42, CNTROB, CSNK2A2, GOPC, HOOK1, HRB, OAZ3, ODF1, RIMBP3, SPATA16) that are essential for spermatogenesis. Mouse or rat mutants in these genes are primarily associated with oligoasthenoteratozoospermia, since they are involved in sperm morphogenesis. However, the phenotype spectrum may comprise also azoospermia. The purpose of the thesis was to determine the sequence of the afore mentioned genes in infertile men with impaired spermatogenesis and to reveal presence or absence of pathogenic mutations in these genes, using cDNA and genomic DNA from peripheral blood. The candidate genes were...
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The role of centrobin in spermatogenesis
Flintová, Jennifer ; Komrsková, Kateřina (advisor) ; Šebková, Nataša (referee)
Spermatogenesis is a highly orchestrated, strictly regulated cascade of events that could be divided into three major processes: mitotic expansion of diploid germ cells (spermatocytogenesis), meiotic division creating haploid cells, and spermiogenesis. Spermiogenesis, the final stage of spermatogenesis comprises a striking metamorphosis of round haploid spermatids into morphologically and functionally specialized spermatozoa designed for the fertilization. One of the proteins indispensable for proper sperm morphogenesis is centrobin, a structural component of the specialized cytoskeletal structures of the elongating spermatids (acroplaxome and manchette), executing essential role in sperm head shaping and assembly of the head-tail coupling apparatus. Disruption in Cntrob gene (coding for centrobin) in rats homozygous at the hd (hypodactyly) locus results in male infertility, with a striking morphological signature called "decapitated sperm syndrome" with detachment of sperm head from the flagellum due to impaired head-tail coupling. However, molecular function of centrobin in spermiogenesis is still unknown. Sperm decapitation is a distinct phenotype described in several mouse mutants and importantly from infertile human males. Strikingly, in addition to proteins functioning in cytoskeletal...
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Effect of ubiquitin-proteasome system on spermiogenesis in mammals
Kroumanová, Kristýna ; Petelák, Aleš (advisor) ; Krejčová, Tereza (referee)
Spermiogenesis is a complicated process in which the haploid spermatids differentiate into morphologically mature sperm. Morphological changes include condensation of chromatin and histone-to-protamine replacement, fusion of Golgi-derived vesicles to form acrosomal cap, flagellum formation, reduction of cytoplasmic volume and organelles rearrangement. Ubiquitin-proteasome system plays a key role in these processes. Ubiquitination is a posttranslational modification, leading to the labelling of intracellular proteins targeted for degradation by 26S proteasome. Importance of sperm ubiquitination, is supported by the fact, that deficiency of ubiquitin-proteasome system can lead to infertility at various degrees. During the subsequent sperm maturation in the epididymis extracellular ubiquitination of abnormal sperm and sperm quality control take place. Ubiquitin-proteasome system plays a key role during fertilization, when the sperm 26S proteasome is co-responsible in zona pellucida penetration. The purpose of this assay is to describe the effect of ubiquitin- proteasome system during different stages of spermiogenesis in mammals.
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Targeted next generation sequencing of candidate genes responsible for impaired spermatogenesis and male infertility
Daňková, Michaela ; Liška, František (advisor) ; Holá, Dana (referee)
Infertility is a widespread health problem, caused by the male factor in about half of all cases, and in about a half of the infertile men the cause is unknown. In a significant number of these men, genetic etiology is assumed. Current routine methods of laboratory diagnostics, which include karyotype examination, exclusion of mutations in the CFTR gene, and Y chromosome microdeletions, do not usually reveal the cause of infertility. That is why researchers' efforts aim at detecting mutations in other genes that are causing male infertility. In recent years, animal models have been used to identify many genes necessary for fertility. Based on these findings, 12 candidate genes have been selected (CAPZA3, CDC14B, CDC42, CNTROB, CSNK2A2, GOPC, HOOK1, HRB, OAZ3, ODF1, RIMBP3, SPATA16) that are essential for spermatogenesis. Mouse or rat mutants in these genes are primarily associated with oligoasthenoteratozoospermia, since they are involved in sperm morphogenesis. However, the phenotype spectrum may comprise also azoospermia. The purpose of the thesis was to determine the sequence of the afore mentioned genes in infertile men with impaired spermatogenesis and to reveal presence or absence of pathogenic mutations in these genes, using cDNA and genomic DNA from peripheral blood. The candidate genes were...
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