@article{ErbeldingDenkSchroderSchartletal.1994,
  author    = {Erbelding-Denk, Claudia and Schroder, Johannes H. and Schartl, Manfred and Nanda, Indrajit and Schmid, Michael and Epplen, J{\"o}rg T.},
  title     = {Male polymorphism in Limia perugiae (Pisces: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61573},
  year      = {1994},
  abstract  = {The male-polymorphic poeciliid fish, Limia perugiae, a small teleostean endemic to the southeast of the Caribbean island Hispafiola, consists of three male size morphs with uniform females. Large males differentiate at a size va:rying between 25 and 38 mm; intermediate males, between 21 and 25 mm. Under competition, !arge males exhibit an elaborate courtship display, whereas small males show only a sneak-chase behavior. Intermediate males adapt their tactics to the respective competitors. However, all malemorphs can switch from courtship display to sneak-chase behavior. In large mating groups with four males of different size and five or six virgin females, large dominant a-males as weil as small subordinate \(\delta\)-males did not produce any offspring. Unexpectedly, all progeny were sired exclusively by the intemediate subordinate ß- and \(\gamma\)-males. Breeding experiments with the three male morphs can best be explained by a model of Y -linked genes for small and !arge size which are both suspended by the activity of an autosomal recessive repressor responsible for the development of intermediate males. The dominant allele of the recessive repressor, in either its homoorits heterozygous state, activates the Y-chromosomal genes for !arge or small size, respectively. Accordingly, intermediate males may produce male offspring of all size classes, depending on the presence of either the Y-linked gene or the autosomal repressor.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@phdthesis{Saumweber2011,
  author    = {Saumweber, Timo},
  title     = {Mechanism of Learning and Plasticity in Larval Drosophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66354},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {According to a changing environment it is crucial for animals to make experience and learn about it. Sensing, integrating and learning to associate different kinds of modalities enables animals to expect future events and to adjust behavior in the way, expected as the most profitable. Complex processes as memory formation and storage make it necessary to investigate learning and memory on different levels. In this context Drosophila melanogaster represents a powerful model organism. As the adult brain of the fly is still quite complex, I chose the third instar larva as model - the more simple the system, the easier to isolate single, fundamental principles of learning. In this thesis I addressed several kinds of questions on different mechanism of olfactory associative and synaptic plasiticity in Drosophila larvae. I focused on short-term memory throughout my thesis. First, investigating larval learning on behavioral level, I developed a one-odor paradigm for olfactory associative conditioning. This enables to estimate the learnability of single odors, reduces the complexity of the task and simplify analyses of "learning mutants". It further allows to balance learnability of odors for generalization-type experiments to describe the olfactory "coding space". Furthermore I could show that innate attractiveness and learnability can be dissociated and found finally that paired presentation of a given odor with reward increase performance, whereas unpaired presentations of these two stimuli decrease performance, indicating that larva are able to learn about the presence as well as about the absence of a reward. Second, on behavioral level, together with Thomas Niewalda and colleagues we focussed on salt processing in the context of choice, feeding and learning. Salt is required in several physiological processes, but can neither be synthesized nor stored. Various salt concentrations shift the valence from attraction to repulsion in reflexive behaviour. Interestingly, the reinforcing effect of salt in learning is shifted by more than one order of magnitude toward higher concentrations. Thus, the input pathways for gustatory behavior appear to be more sensitive than the ones supporting gustatory reinforcement, which is may be due to the dissociation of the reflexive and the reinforcing signalling pathways of salt. Third, in cooperation with Michael Schleyer we performed a series of behavioral gustatory, olfactory preference tests and larval learning experiments. Based on the available neuroanatomical and behavioral data we propose a model regarding chemosensory processing, odor-tastant memory trace formation and the 'decision' like process. It incorporates putative sites of interaction between olfactory and gustatory pathways during the establishment as well as behavioral expression of odor-tastant memory. We claim that innate olfactory behavior is responsive in nature and suggest that associative conditioned behavior is not a simple substitution like process, but driven more likely by the expectation of its outcome. Fourth, together with Birgit Michels and colleagues we investigated the cellular site and molecular mode of Synapsin, an evolutionarily conserved, presynaptic vesicular phosphoprotein and its action in larval learning. We confirmed a previously described learning impairment upon loss of Synapsin. We localized this Synapsin dependent memory trace in the mushroom bodies, a third-order "cortical" brain region, and could further show on molecular level, that Synapsin is as a downstream element of the AC-cAMP-PKA signalling cascade. This study provides a comprehensive chain of explanation from the molecular level to an associative behavioral change. Fifth, in the main part of my thesis I focused on molecular level on another synaptic protein, the Synapse associated protein of 47kDa (Sap47) and its role in larval behavior. As a member of a phylogenetically conserved gene family of hitherto unknown function. It is localized throughout the whole neuropil of larval brains and associated with presynaptic vesicles. Upon loss of Sap47 larvae exhibit normal sensory detection of the to-be-associated stimuli as well as normal motor performance and basic synaptic transmission. Interestingly, short-term plasticity is distorted and odorant-tastant associative learning ability is reduced. This defect in associative function could be rescued by restoring Sap47 expression. Therefore, this report is the first to suggest a function for Sap47 and specifically argues that Sap47 is required for synaptic as well as for behavioral plasticity in Drosophila larva. This prompts the question whether its homologs are required for synaptic and behavioral plasticity also in other species. Further in the last part of my thesis I contributed to the study of Ayse Yarali. Her central topic was the role of the White protein in punishment and relief learning in adult flies. Whereas stimuli that precede shock during training are subsequently avoided as predictors for punishment, stimuli that follow shock during training are later on approached, as they predict relief. Concerning the loss of White we report that pain-relief learning as well as punishment learning is changed. My contribution was a comparison between wild type and the white1118 mutant larvae in odor-reward learning. It turned out that a loss of White has no effect on larval odorant-tastant learning. This study, regarding painrelief learning provides the very first hints concerning the genetic determinants of this form of learning.},
  subject      = {Taufliege},
  language  = {en}
}
@article{MeyerMorrisseySchartl1994,
  author    = {Meyer, Axel and Morrissey, Jean M. and Schartl, Manfred},
  title     = {Recurrent origin of a sexually selected trait in Xiphophorus fishes inferred from a molecular phylogeny},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61569},
  year      = {1994},
  abstract  = {DARWIN\(^1\) believed that sexual selection accounts for the evolution of exaggerated male ornaments, such as the sword-like caudal fin extensions of male fishes of the genus Xiphophorus, that appear detrimental to survival. Swordtails continue to feature prominently in empirical work and theories of sexual selection; the pre-existing bias hypothesis has been offered as an explanation for the evolution of swords in these fishes\(^{2,3}\). Based upon a largely morphological phylogeny, this hypothesis suggests that female preference to mate with sworded males arose in ancestrally swordless species, thus pre-dating the origin of the sword itself and directly driving its evolution. Here we present a molecular phylogeny (based on mitochondrial and nuclear DNA sequences) of Xiphophorus which differs from the traditional one: it indicates that the sword originated and was lost repeatedly. Our phylogeny suggests that the ancestor of the genus is more likely to have possessed a sword than not, thus questioning the applicability of the pre-existing bias hypothesis as an explanation for the cvolution of this sexually selected trait.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{MalitschekWittbrodtFischeretal.1994,
  author    = {Malitschek, Barbara and Wittbrodt, Joachim and Fischer, Petra and Lammers, Reiner and Ullrich, Axel and Schartl, Manfred},
  title     = {Autocrine stimulation of the Xmrk receptor tyrosine kinase in Xiphophorus melanoma cells and identification of a source for the physiological ligand},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61551},
  year      = {1994},
  abstract  = {The melanoma·inducing gene of Xiphophorus fish encodes the Xmrk receptor tyrosine kinase. U sing a highly specific antiserum p~oduced against the recombinant receptor expressed with a baculovirus, it is shown that Xmrk is the most abundant phosphotyrosine protein in fish melanoma and thus highly activated in the tumors. Studies on a melanoma cellline revealed that these cells produce an activity that considerably stimulates receptor autophosphorylation. The stimulating activity induces receptor down-regulation and can be depleted from the melanoma cellsupernatant by the immobilized recombinant receptor protein. The fish melanoma cells can thus be considered autocrine tumor cells providing a source for future purification and characterization of the Xmrk ligand.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{GoetzKoesterWinkleretal.1994,
  author    = {G{\"o}tz, Rudolf and K{\"o}ster, Reinhard and Winkler, Christoph and Raulf, Friedrich and Lottspeich, Friedrich and Schartl, Manfred and Thoenen, Hans},
  title     = {Neurotrophin-6 is a new member of the nerve growth factor family},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61544},
  year      = {1994},
  abstract  = {DURING vertebrale development, many neurons depend for survival and differentiation on their target cells\(^{1-3}\). The best documented mediator of such a retrograde trophic action is the neurotrophin nerve growth factor (NGF)\(^1\). NGF and the other known members of tbe neurotrophin family, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT -3) and neurotrophin-4/5 (NT -4/5) are conserved as distinct genes over large evolutionary distances\(^{4 -6}\). Here we report the cloning of neurotrophin-6 (NT -6), a new member of this family from the teleost fish Xiphophorus. NT -6 distinguishes itself from the other known neurotrophins in that it is not found as a soluble protein in the medium of producing cells. The addition of heparin (but not chondroitin) effects the release of NT -6 from cell surface and extracellular matrix molecules. Recombinant purified NT -6 has a spectrum of actions similar to NGF on chick sympathetic and sensory neurons, albeit with a lower potency. NT -6 is expressed in tbe embryonie valvulla cerebelli; expression persists in some adult tissues. The interaction of NT-6 with heparin-binding molecuJes may modulate its action in the nervous system .},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@phdthesis{Pahl2011,
  author    = {Pahl, Mario},
  title     = {Honeybee Cognition: Aspects of Learning, Memory and Navigation in a Social Insect},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66165},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Honeybees (Apis mellifera) forage on a great variety of plant species, navigate over large distances to crucial resources, and return to communicate the locations of food sources and potential new nest sites to nest mates using a symbolic dance language. In order to achieve this, honeybees have evolved a rich repertoire of adaptive behaviours, some of which were earlier believed to be restricted to vertebrates. In this thesis, I explore the mechanisms involved in honeybee learning, memory, numerical competence and navigation. The findings acquired in this thesis show that honeybees are not the simple reflex automats they were once believed to be. The level of sophistication I found in the bees' memory, their learning ability, their time sense, their numerical competence and their navigational abilities are surprisingly similar to the results obtained in comparable experiments with vertebrates. Thus, we should reconsider the notion that a bigger brain automatically indicates higher intelligence.},
  subject      = {Biene},
  language  = {en}
}
@phdthesis{Niewalda2010,
  author    = {Niewalda, Thomas},
  title     = {Neurogenetic analyses of pain-relief learning in the fruit fly},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65035},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {All animals learn in order to cope with challenges imposed on them by their environment. This is true also for both larval and adult fruit flies as exemplified in pavlovian conditioning. The focus of this Thesis is on various aspects of the fruit flies learning ability. My main project deals with two types of learning which we call punishment-learning and pain-relief learning. Punishment learning happens when fruit flies are exposed to an odour which is followed by electric shock. After such training, flies have learned that that odour signals pain and consequently will avoid it in the future. If the sequence of the two stimuli is reversed such that odour follows shock, flies learn the odour as a signal for relief and will later on approach it. I first report a series of experiments investigating qualitative and parametric features of relief-learning; I find that (i) relief learning does result from true associative conditioning, (ii) it requires a relatively high number of training trials, (iii) context-shock training is ineffective for subsequent shock-odour learning. A further question is whether punishment-learning and pain-relief learning share genetic determinants. In terms of genetics, I test a synapsin mutant strain, which lacks all Synapsin protein, in punishment and relief-learning. Punishment learning is significantly reduced, and relief-learning is abolished. Pan-neuronal RNAi-mediated knock-down of Synapsin results in mutant-like phenotypes, confirming the attribution of the phenotype to lack of Synapsin. Also, a rescue of Synapsin in the mushroom body of syn97 mutants restores both punishment- and relief-learning fully, suggesting the sufficiency of Synapsin in the mushroom body for both these kinds of learning. I also elucidate the relationship between perception and physiology in adult fruit flies. I use odour-shock conditioning experiments to identify degrees of similarity between odours; I find that those similarity measures are consistent across generalization and discrimination tasks of diverse difficulty. Then, as collaborator of T. V{\"o}ller and A. Fiala, I investigate how such behavioural similarity/dissimilarity is reflected at the physiological level. I combine the behaviour data with calcium imaging data obtained by measuring the activity patterns of those odours in either the sensory neurons or the projection neurons at the antennal lobe. Our interpretation of the results is that the odours perceptual similarity is organized by antennal lobe interneurons. In another project I investigate the effect of gustatory stimuli on reflexive behaviour as well as their role as reinforcer in larval learning. Drosophila larvae greatly alter their behaviour in presence of sodium chloride. Increasing salt concentration modulates choice behaviour from weakly appetitive to strongly aversive. A similar concentration-behaviour function is also found for feeding: larval feeding is slightly enhanced in presence of low salt concentrations, and strongly decreased in the presence of high salt concentrations. Regarding learning, relatively weak salt concentrations function as appetitive reinforcer, whereas high salt concentrations function as aversive reinforcer. Interestingly, the behaviour-concentration curves are shifted towards higher concentrations from reflexive behaviour (choice behaviour, feeding) as compared to associative learning. This dissociation may reflect a different sensitivity in the respective sensory-motor circuitry.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Heddergott2011,
  author    = {Heddergott, Niko},
  title     = {Zellbiologische Aspekte der Motilit{\"a}t von Trypanosoma brucei unter Ber{\"u}cksichtigung der Interaktion mit der Mikroumwelt},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-56791},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Trypanosomen sind Protozoen, die Krankheiten bei Mensch und Tier verursachen, die unbehandelt infaust verlaufen. Die Zellen sind hoch motil, angetrieben von einem einzelst{\"a}ndigen Flagellum, welches entlang des Zellk{\"o}rpers angeheftet ist. Selbst in Zellkultur h{\"o}ren Trypanosomen niemals auf sich zu bewegen und eine Ablation funktioneller Bestandteile des Flagellarapparates ist letal f{\"u}r Blutstromformen. Es wurde gezeigt, dass Motilit{\"a}t notwendig ist f{\"u}r die Zellteilung, Organellenpositionierung und Infektiosit{\"a}t. Dies macht Trypanosomen zu besonders geeigneten Modellorganismen f{\"u}r die Untersuchung der Motilit{\"a}t. Dennoch ist erstaunlich wenig {\"u}ber die Motilit{\"a}t bei Trypanosomen bekannt. Dies gilt auch noch genereller f{\"u}r die Protozoen. Unl{\"a}ngst ist dieses Gebiet allerdings in den Fokus vieler Arbeiten ger{\"u}ckt, was bereits erstaunliche, neue Erkenntnisse hervorgebracht hat. Doch Vieles ist noch nicht abschliessend gekl{\"a}rt, so z.B. wie der Flagellarschlag genau reguliert wird, oder wie sich der Schlag des Flagellums entlang des Zellk{\"o}rpers ausbreitet. Die vorliegende Arbeit befasst sich besonders mit den Einfl{\"u}ssen, die die Mikroumgebung auf die Motilit{\"a}t von Blutstromform-Trypanosomen aus{\"u}bt. In ihrem nat{\"u}rlichen Lebensraum finden sich Trypanosomen in einer hoch komplexen Umgebung wieder. Dies gilt sowohl f{\"u}r den Blutkreislauf, als auch f{\"u}r den Gewebezwischenraum in ihrem S{\"a}ugerwirt. Die hohe Konzentration von Zellen, Gewebeverb{\"a}nden und extrazellul{\"a}ren Netzwerken k{\"o}nnte man als Ansammlung von Hindernissen f{\"u}r die Fortbewegung auffassen. Diese Arbeit zeigt dagegen, dass der Mechanismus der Bewegung eine Adaptation an genau diese Umweltbedingungen darstellt, so z.B. an die Viskosit{\"a}t von Blut. Es wird auch ein Bewegungsmodell vorgestellt, das erl{\"a}utert, worin diese Adaption besteht. Dies erkl{\"a}rt auch, warum die Mehrheit der Zellen einer Trypanosomenkultur eine ungerichtete Taumel-Bewegung aufweist in nieder-viskosem Medium, das keine solchen "Hindernisse" enth{\"a}lt. Die Zugabe von Methylcellulose in einer Konzentration von ca. 0,5\% (w/v) erwies sich als geeigneter Ersatz von Blut, um optimale Bedingungen f{\"u}r gerichtetes Schwimmen von Blutstromform Trypanosomen zu erreichen. Zus{\"a}tzlich wurden in dieser Arbeit unterschiedliche Arten von Hindernissen, wie Mikroperlen (Beads) oder molekulare Netzwerke, sowie artifizielle, geordnete Mikrostrukturen verwendet, um die Interaktion mit einer festen Matrix zu untersuchen. In deren Anwesenheit war sowohl die Schwimmgeschwindigkeit, als auch der Anteil an persistent schwimmenden Trypanosomen erh{\"o}ht. Zellen, die frei schwimmend in Fl{\"u}ssigkeiten vorkommen (wie Euglena oder Chlamydomonas), werden effizient durch einen planaren Schlag des Flagellums angetrieben. Trypanosomen hingegen mussten sich evolution{\"a}r an eine komplexe Umgebung anpassen, die mit einer zu raumgreifenden Welle interferieren w{\"u}rde. Der dreidimensionale Flagellarschlag des, an die Zelloberfl{\"a}che angehefteten, Flagellums erlaubt den Trypanosomen eine effiziente Fortbewegung durch die Interaktion mit Objekten in jedweder Richtung gleichermassen. Trypanosomen erreichen dies durch eine hydrodynamisch verursachte Rotation ihres Zellk{\"o}rpers entlang ihrer L{\"a}ngsachse, entgegen dem Uhrzeigersinn. Der Einfluss der Mikroumgebung wurde in fr{\"u}heren Untersuchungen bisher vernachl{\"a}ssigt, ist zum Verst{\"a}ndnis der Motilit{\"a}t von T. brucei jedoch unerl{\"a}sslich. Ein weiterer, bisher nicht untersuchter Aspekt der Beeinflussung der Motilit{\"a}t durch die Umwelt sind hydrodynamische Str{\"o}mungseffekte, denen Trypanosomen im kardiovaskul{\"a}ren System ausgesetzt sind. Diese wurden in dieser Arbeit mittels Mikrofluidik untersucht. Um unser Verst{\"a}ndnis der Motilit{\"a}t von Trypanosomen von 2D, wie {\"u}blich in der Motilit{\"a}tsanalyse mittels Lebend-Zell-Mikroskopie, auf drei Dimensionen auszudehnen, wurde als bildgebendes Verfahren auch die Holographie eingesetzt. Mikrofluidik und Holographie sind beides aufkommende Techniken mit großem Anwendungspotential in der Biologie, die zuvor noch nie f{\"u}r die Motilit{\"a}tsanalyse von Trypanosomen eingesetzt worden waren. Dies erforderte daher interdisziplin{\"a}re Kooperationen. Zus{\"a}tzlich wurde in dieser Arbeit auch ein vollst{\"a}ndig automatisiertes und Software-gesteuertes Fluoreszenzmikroskopiesystem entwickelt, das in der Lage ist, einzelne Zellen durch entsprechende Steuerung des Mikroskoptisches autonom zu verfolgen und somit eine Bewegungsanalyse in Echtzeit erm{\"o}glicht, ohne weitere Benutzerinteraktion. Letztendlich konnte dadurch auch die Bewegung der schlagenden Flagelle und des gesamten Zellk{\"o}rpers mit hoher zeitlicher und r{\"a}umlicher Aufl{\"o}sung mittels Hochgeschwindigkeits-Fluoreszenzmikroskopie aufgekl{\"a}rt werden.},
  subject      = {Trypanosoma brucei},
  language  = {de}
}
@misc{Wenzel2011,
  type      = {Master Thesis},
  author    = {Wenzel, Frank},
  title     = {Smell and repel: Resin based defense mechanisms and interactions between Australian ants and stingless bees},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65960},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Bees are subject to permanent threat from predators such as ants. Their nests with large quantities of brood, pollen and honey represent lucrative targets for attacks whereas foragers have to face rivalry at food sources. This thesis focused on the role of stingless bees as third party interactor on ant-aphid-associations as well as on the predatory potential represented by ants and defense mechanisms against this threat. Regular observations of an aphid infested Podocarpus for approaching stingless bees yielded no results. Another aim of this thesis was the observation of foraging habits of four native and one introduced ant species for assessment of their predatory potential to stingless bees. All species turned out to be dietary balanced generalists with one mostly carnivorous species and four species predominantly collecting nectar roughly according to optimal foraging theory. Two of the species monitored, Rhytidoponera metallica and Iridomyrmex rufoniger were considered potential nest robbers. As the name implies, stingless bees lack the powerful weapon of their distant relatives; hence they specialized on other defense strategies. Resin is an important, multipurpose resource for stingless bees that is used as material for nest construction, antibiotic and for defensive means. For the latter purpose highly viscous resin is either directly used to stick down aggressors or its terpenic compounds are included in the bees cuticular surface. In a feeding choice experiment, three ant species were confronted with the choice between two native bee species - Tetragonula carbonaria and Austroplebeia australis - with different cuticular profiles and resin collection habits. Two of the ant species, especially the introduced Tetramorium bicarinatum did not show any preferences. The carnivorous R. metallica predominantly took the less resinous A. australis as prey. The reluctance towards T. carbonaria disappeared when the resinous compounds on its cuticle had been washed off with hexane. To test whether the repulsive reactions were related to the stickiness of the resinous surface or to chemical substances, hexane extracts of bees' cuticles, propolis and three natural tree resins were prepared. In the following assay responses of ants towards extract treated surfaces were observed. Except for one of the resin extracts, all tested substances had repellent effects to the ants. Efficacy varied with the type of extract and species. Especially to the introduced T. bicarinatum the cuticular extract had no effect. GCMS-analyses showed that some of the resinous compounds were also found in the cuticular profile of T. carbonaria which featured reasonable analogies to the resin of Corymbia torelliana that is highly attractive for stingless bees. The results showed that repellent effects were only partially related to the sticky quality of resin but were rather caused by chemical substances, presumably sesqui- and diterpenes. Despite its efficacy this defense strategy only provides short time repellent effects sufficient for escape and warning of nest mates to initiate further preventive measures.},
  subject      = {Stachellose Biene},
  language  = {en}
}
@phdthesis{ElHajj2011,
  author    = {El Hajj, Nady},
  title     = {Epimutations in Germ-Cell and Embryo Development: Possible Consequences for Assisted Reproduction},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65995},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Assisted reproductive technologies (ART) emerged in the late 1970's as a therapy for human infertility. Up till now more than 3 million babies have been conceived through ART, demonstrating the safety and efficiency of the technique. Published reports showed an increase in the rate of imprinting disorders (Beckwith Wiedemann Syndrome, Angelman Syndrome, etc.) in babies born after ART. What are the effects imposed through ART and should researchers reassess its safety and implications on the future offspring? Throughout this thesis, I analyzed the methylation patterns of germ cells and embryos to determine whether in vitro maturation and in vitro fertilization have a negative impact on the epigenetic patterns. Furthermore, DNA methylation was compared between sperm of infertile and presumably fertile controls in order to understand whether epigenetic disturbances lead to infertility at the first place. The occurrence of methylation aberrations in germ cells of infertile patients could be transmitted to new-borns and then cause epigenetic disorders. In order to elucidate the imprinting status within single cells, I developed a new technique based on limiting dilution where bisulfite treated DNA is distributed across several wells before amplification. This allowed methylation measurement at the single allele level as well parent of origin detection. In a total of 141 sperm samples from couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) including 106 with male factor or combined infertility and 28 with female infertility, I detected a significant correlation between lower quality of semen parameters (sperm count, percentage of abnormal sperm, and percentage of motile sperm) and the rate of imprinting errors. ALU repeats displayed a higher methylation in sperm DNA of patients leading to a pregnancy and live birth, compared to patients in which pregnancy was not achieved or a spontaneous abortion occurred. A discriminant analysis based on ALU methylation allowed correct classification of >70\% of cases. Preliminary data from illumina methylation arrays where more than 27,000 CpGs were analyzed determined that only a single CpG site from the open reading frame C14orf93 was significantly different between the infertile and presumably fertile control group. However, further improvements on data normalization might permit detection of other differentially methylated regions. Comparison of embryos after natural conception, in vitro fertilized embryos from superovulated oocytes, and embryos achieved through fertilization of in vitro cultured oocytes revealed no dramatic effect on the imprinting patterns of Igf2r, H19, and Snrpn. Oocyte cryotop vitrification did not result in a dramatic increase of imprinting mutations in oocytes even though the rate of sporadic methylation errors in single Snrpn CpGs were higher within the in-vitrified group. Collectively, the results I will present within this thesis suggest an increase in the rate of imprinting errors within the germ cells of infertile patients, in addition to a decrease in genome wide methylation of ALU repetitive elements. I did not observe a detrimental effect on the methylation patterns of oocytes and the resulting embryos using in vitro maturation of oocytes and/or standard IVF with in vivo grown superovulated oocytes.},
  subject      = {Reproduktionsmedizin},
  language  = {en}
}