Female gametes, or oocytes grow and mature in a niche environment maintained by the somatic cells of the ovarian follicle. At ovulation ovarian follicle cells respond to the luteinising hormone (LH) surge coordinating the final maturation, meiotic resumption and release of oocytes. Simultaneously, production of a unique “mucified” extracellular matrix surrounding the oocyte through synthesis of Hyaluronan (HA) and HA cross-linking proteins produces an “expanded” and stabilised cumulus oocyte matrix with a specific composition, structure and function. In vitro maturation (IVM) of oocytes is a procedure by which cumulus oocyte complexes (COCs) are stimulated to produce cumulus matrix and undergo oocyte maturation ex vivo. In vitro maturation is a useful procedure for studying oocyte competence as well as offering health benefits for patients undergoing assisted reproduction. Oocytes derived from IVM have much lower developmental competence than in vivo matured oocytes, likely as a result of altered environmental conditions and gene expression leading to suboptimal maturation and/or inappropriate metabolic control in oocytes. Cumulus matrix expansion is widely used as an indicator of good oocyte developmental potential, however, the mechanism(s) that endow oocyte quality and how these may be influenced by the cumulus matrix are poorly understood. To better understand the process by which cumulus matrix is linked to the final stages of oocyte maturation, I undertook investigation of mouse COC matrix composition and function after in vivo maturation in comparison to IVM. The gene responsible for Hyaluronan synthesis, Has2, was not impaired under IVM conditions. In contrast, two key extracellular matrix proteins; Versican and Adamts1, which are normally selectively incorporated into periovulatory COCs in vivo, were greater than 10-fold reduced in IVM whether stimulated with Egf and/or FSH. This work is the first to show that commonly used IVM conditions result in altered gene expression in cumulus cells. Furthermore, the absence of Adamts1 and Versican suggest that COC matrix may be functionally insufficient. Although associated with good developmental potential, the function of the COC matrix in oocyte maturation is unknown. I assessed the properties of COC matrix that control metabolite supply to oocytes by examining transport of fluorescently labelled glucose and cholesterol across mouse COCs. Profound differences in the control of metabolite supply to oocytes in IVM were observed. In vivo matured complexes were capable of excluding glucose from the entire COC and cholesterol was excluded from oocytes. Conversely IVM COCs were more permissive to rapid equilibration of glucose and cholesterol concentrations across the complex and in oocytes. In fact both metabolites accumulated rapidly in IVM oocytes resulting in inverse gradient patterns of glucose and cholesterol abundance with highest concentrations accumulating in the oocyte after IVM vs highest concentrations surrounding the COC after in vivo maturation conditions. As oocytes are highly sensitive to high glucose my results indicate that metabolic balance in IVM may be disrupted due to impaired molecular filtration properties of the mucified COC matrix that controls supply of hydrophilic and lipophylic substrates. Importantly these novel findings can explain the glucose sensitivity of IVM oocytes and identifies a mechanism by which IVM may lead to poorer oocyte developmental competence. To translate these findings into the improvement of IVM I generated recombinant expression plasmid constructs for several Adamts1 and Versican functional domains. The efficacy of Versican as an IVM supplement that activates cumulus cell signal transduction was proved in principle, by showing enhanced COC matrix expansion when added to mouse IVM cultures. Similar mechanisms are likely to be functional in human COCs since I demonstrated VERSICAN and ADAMTS1 expression in human in vivo matured cumulus and granulosa cells. This work has advanced our understanding of oocyte maturation and will lead to improvements in IVM and healthier outcomes from reproductive therapies. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342419 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, 2004. / Bibliyografya var.

Thesis (Ph. D.)--Miami University, Dept. of Zoology, 2004. / Title from second page of PDF document. Includes bibliographical references (p. 116-127).

Thesis (PhD)--University of Mastericht, the Netherlands, 2007. / Includes bibliographical references.

Το σύνδρομο πολυκυστικών ωοθηκών (PCOS) αποτελεί την πιο συχνή ενδοκρινολογική διαταραχή των γυναικών αναπαραγωγικής ηλικίας που χαρακτηρίζεται από κεντρικού τύπου παχυσαρκία, ακμή , υπερτρίχωση και διαταραχές των εμμηνορησιακών κύκλων που οφείλονται στην υπερανδρογοναιμία και την χρόνια ανωοθυλακιορρηξία. Οι γυναίκες με PCOS αναπτύσσουν και μεταβολικού τύπου διαταραχές όπως η υπερινσουλιναιμία λόγω αντίστασης στην ινσουλίνη, η υπέρταση, ο σακχαρώδης διαβήτης, η δυσλιπιδαιμία και το μεταβολικό σύνδρομο. Σημαντικό ρόλο στην παθοφυσιολογία της των παραπάνω μεταβολικών διαταραχών ασκεί το σύστημα Ρενίνης-Αγγειοτενσίνης-Αλδοστερόνης (Renin-Angiotensin-Aldosterone System – RAAS) που διακρίνεται σε ενδοκρινές κι ιστικό. Στο ιντρόνιο 16 του γονιδίου του ενζύμου ACE(17q23) έχει βρεθεί ο πολυμορφισμός I/D που προκύπτει από την παρουσία ( Insertion– I) ή την απουσία (Deletion–D) μιας Αlu αλληλουχίας μήκους 287 bp, δημιουργώντας τρείς διακριτούς γονότυπους: II, ID και DD Με δεδομένο το ρόλο του συστήματος RAAS σε σχέση με τους παράγοντες κινδύνου για καρδιαγγειακή νόσο και κυρίως με την αντίσταση στην ινσουλίνη, ο ρόλος του πολυμορφισμού ACE I/D έχει καταστεί αντικείμενο μελέτης ως προς την εκδήλωση καρδιαγγειακών συμβαμάτων. Στην παρούσα μελέτη προσδιορίστηκε ο πολυμορφισμός ACE I/D σε 156 φυσιολογικές γυναίκες και σε 212 γυναίκες με την πιο βαριά μορφή του συνδρόμου πολυκυστικών ωοθηκών που είναι η ύπαρξη βιοχημικής υπερανδρογοναιμίας και χρόνιας ανωοθυλακιορηξίας. Το συμπέρασμα μετά τη στατιστική ανάλυση ήταν ότι ο γονότυπος ΙΙ συνδέεται στατιστικώς σημαντικά με την την αντίσταση στην ινσουλίνη κι ο γονότυπος ΙD με τα επίπεδα της 17-OH προγεστερόνης, πρόδρομης ορμόνης κατά την βιοσύνθεση των ανδρογόνων που ίσως σημαίνει με τοπικά αυξημένη ενεργότητα του RAS. Tα ευρήματα αυτά ανάγουν τον πολυμορφισμό της ACE σε ένα πιθανά πολύτιμο δείκτη αυξημένου καρδιαγγειακού κινδύνου στις γυναίκες με PCOS. / The polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women of reproductive age, characterized by central obesity, acne, hirsutism and disorders menstrual cycles due to hyperandrogonemia and chronic anovulation. Women with PCOS develop type and metabolic disorders such as hyperinsulinemia due to insulin resistance, hypertension, diabetes mellitus, dyslipidemia and metabolic syndrome. Important role in the pathophysiology of these metabolic disorders has the renin-angiotensin-aldosterone system (Renin-Angiotensin-Aldosterone System - RAAS), which is divided into endocrine and tissue. In intron 16 of the gene of the enzyme ACE (17q23) has found a polymorphism I / D resulting from the presence (Insertion-I) or absence (Deletion-D) of an Alu sequence length of 287 bp, creating three distinct genotypes: II,ID,DD. Given the role of the RAAS system in relation to risk factors for cardiovascular disease and especially with insulin resistance, the role of polymorphism ACE I / D has become a subject of study as to the occurrence of cardiovascular events. This study identified a polymorphism ACE I / D in 156 healthy women and 212 women with the most severe form of polycystic ovarian syndrome is the presence of biochemical hyperandrogonemia and chronic anovulation. The conclusion after statistical analysis was that the II genotype is associated statistically significant with insulin resistance and ID genotype with levels of 17-OH progesterone hormone precursor in the biosynthesis of androgens which it might means locally increased activity of RAS. These findings suggest the polymorphism of the ACE in a potentially valuable indicator of increased cardiovascular risk in women with PCOS.

Made available in DSpace on 2014-06-11T19:30:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-09-29Bitstream added on 2014-06-13T19:40:13Z : No. of bitstreams: 1 ribeiro_k_dr_jabo.pdf: 876100 bytes, checksum: b597a24953597a3c3b054ab257922bbb (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O presente trabalho realizou o estudo dos aspectos estruturais do hepatopâncreas, ovários e da caracterização hormonal de fêmeas de Macrobrachium amazonicum, nos diferentes estágios de maturação gonadal. Para tanto utilizaram-se 150 fêmeas adultas subdivididas entre os cinco diferentes estágios de maturação ovariana. Após serem capturados os animais foram pesados e mortos por choque térmico. Ovários e hepatopâncreas foram coletados e pesados individualmente para obtenção dos índices gonadossomático (IGS) e hepatossomático (IHS). Para as análises de microscopia de luz e eletrônica de transmissão, ovários e hepatopâncreas foram fixados em solução de Karnovsky e seguiram os procedimentos de rotina de inclusão. Os ovários, hepatopâncreas e hemolinfa destinados à quantificação hormonal foram armazenados em ependorfes e preservados em nitrogênio líquido a -70ºC, para posterior processamento de radioimunoensaio visando avaliação das concentrações de estradiol, progesterona e testosterona. Os resultados relacionados ao IGS e IHS demonstram uma correlação inversa entre os ovários e o hepatopâncreas nos diferentes estágios de maturação gonadal. Em relação ao desenvolvimento ovariano, observa-se a distribuição de cinco tipos celulares ao longo dos cinco estágios de maturação gonadal. Desta forma encontram-se as ovogônias ou células germinativas mais jovens no estágio I de maturação ovariana. As células pré-vitelogênicas, observadas a partir do estágio II, apresentam vesículas de retículo endoplasmático rugoso. Essas vesículas são importantes nas fases de vitelogênese endógena e exógena. Os ovócitos em vitelogênese inicial, característicos do estágio III, apresentam a deposição de vitelo endógeno. As células em vitelogênese avançada, próprias do estágio IV de maturação gonadal, são o alvo principal da vitelogênese... / This study described the structural aspects of the hepatopancreas and ovaries, and the hormonal features of females of the freshwater prawn Macrobrachium amazonicum, during the reproductive cycle. The specimens were captured and killed by thermic chock. The gonadosomatic (GSI) and hepatosomatic (HSI) indices were calculated as the percentage of the weight of the gonad and hepatopancreas to total body weight, respectively. Ovaries and hepatopancreas were fixed in Karnovsky solution and destined to light and ultrastructural microscopy studies. Small portions of the ovary, hepatopancreas and hemolymph were frozen in liquid nitrogen, for later steroid quantification (estradiol, progesterone and testosterone). The relationships between GSI and HSI demonstrate an inverse correlation between ovary and hepatopancreas during the maturation cycle. The oocytes distribution is variable depending on the ovarian maturation degree. The ovary in stage I consists of oogonia. The ovary in stage II consists mainly by previtellogenic oocytes that possess vesicles of the endoplasmic reticulum. These vesicles are important to endogenous and exogenous vitelogenesis. Initial vitellogenic oocytes are mainly observed in the ovary in stage III and possess vitelline reserve, called as endogenous vitelogenesis. Ovary in stage IV is composed of late vitellogenic oocytes that uptake exogenous vitellogenin. Mature oocytes present a corion formation. The hepatopancreas is composed by tubules that are lined by a pseudostratified epithelium, which consists of five cell types, identified as E (embryonic), F (fibrillar), B (blisterlike), R (resorptive) and M (basal). These cells present relationships with digestion and nutrient storage, which are very important for the reproductive processes ...(Complete abstract, click electronic access below)

Submitted by EDER MARQUES DA SILVA null (biodida@yahoo.com.br) on 2016-05-23T19:54:50Z No. of bitstreams: 1 TESE_Eder30 04.pdf: 2779899 bytes, checksum: c45da4458d84767b126f9e3b3af87767 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-05-25T18:03:50Z (GMT) No. of bitstreams: 1 silva_em_dr_bot.pdf: 2779899 bytes, checksum: c45da4458d84767b126f9e3b3af87767 (MD5) / Made available in DSpace on 2016-05-25T18:03:50Z (GMT). No. of bitstreams: 1 silva_em_dr_bot.pdf: 2779899 bytes, checksum: c45da4458d84767b126f9e3b3af87767 (MD5) Previous issue date: 2016-05-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O processo de frutificação é definido como a transição de um ovário em estágio quiescente para estágio de iniciação de formação do fruto. Esta transição é iniciada em resposta aos eventos de polinização e fertilização, os quais induzem o início dos processos fisiológicos e moleculares, que, ao final, irão originar o fruto. A frutificação é fundamental para reprodução nas plantas com flores (Angiospermas). Já foi demonstrado que hormônios (tais como auxina e giberelina) podem atuar em paralelo com fatores de transcrição durante o desenvolvimento do fruto. Alguns desses fatores de transcrição são pós-transcricionalmente regulados por microRNAs. MicroRNAs, são pequenos RNAs (20-22 nt) que regulam pós-transcricionalmente a expressão de genes endógenos, modelando o transcriptoma e a produção de proteínas.Entretanto, vias genéticas orquestradas por microRNAs associadas com o desenvolvimento de ovário, e consequentemente, do fruto em tomateiro (Solanum lycopersicum L.), permanecem pouco exploradas. Neste trabalho, foi investigada a contribuição da via SlymiR159/GAMYB-like durante o processo de desenvolvimento do ovário e frutificação em tomateiro. O miR159 e seus alvos (SlyGAMYB1 e 2) são dinamicamente expressos durante os estágios de desenvolvimento do ovário e consequentemente do fruto. Eventos transgênicos de tomateiro (cv. Micro-Tom) apresentando super-expressão do precursor SlyMIR159 (denominados OE-159) exibiram frutificação precoce quando comparadas aos controles. Notavelmente, todos os eventos OE-159 apresentaram formação de frutos partenocárpicos. Tal alteração no padrão de frutificação pode estar correlacionada a repressão do gene SlyGAMYB1 em períodos pré-antese de desenvolvimento do ovário, é possível que a atividade do fator de transcrição SlyGAMYB1 seja importante para prevenir o início da frutificação antes da polinização. Além disso, a via regulada pelo miR167/SlyARF8A mostrou-se desregulada em ovários pré-antese de plantas transgênicas OE-159. Adicionalmente, mesmo com o fenótipo de partenocarpia e frutificação precoce, não houve alterações na quantidade de hormônios (e.g. giberelina, ácido abscisico e auxina) relacionados à formação de frutos nas plantas transgênicas OE-159. Contudo, a via miR159/GAMYB-like encontra-se reprimida nos primeiros estágios da frutificação (após polinização e fertilização) e a expressão do SlyARF8A (alvo do miR167) encontra-se induzida na presença de auxina. Em conjunto, nossos dados sugerem que o crosstalk entre as vias moduladas pelos microRNAs miR159 e miR167, integrados com a via de sinalização de auxina, é importante para a frutificação em tomateiro. / Fruit set, defined as the shift from quiescent ovary to a fast-growing young fruit, is a key process for fruit production in flowering plants. It has been shown that hormones (such as auxin and gibberellin) act in parallel with transcription factors during fruit set. Some of these are post-transcriptionally regulated by microRNAs (miRNAs). MiRNAs are a group of small non coding RNAs (21-22 nt) that act by regulating post-transcriptionally genes in plants and animals However, microRNA-regulated genetic pathways associated with tomato (Solanum lycopersicum L.) ovary development and fruit set remain poorly exploited. Here, we investigated the functional role of miRNA159/SlyGAMYBlike in tomato ovary development and fruit set. MiR159 and its targets were dynamically expressed in developing flowers, ovaries and fruit tissues. Transgenic tomato (cv. Micro-Tom) plants over-expressing the SlyMIR159 (termed OE-159) exhibited fruit set earlier when compared with control plants. Strikingly, all transgenic lines presented parthenocarpy fruits. Such developmental modification may be a result of the repression of SlyGAMYB1 in pre-anthesis ovaries, our data suggest that SlyGAMYB1 activity is important to prevent fruit set before pollination. In addition as a consequence of this repression, the miR167 node (miR167/SlyARF8 pathway) was mis-regulated in OE-159 ovaries. In addition, we observed that levels of auxin, gibberellin (GA) and abscisic acid (ABA) in pre-anthesis ovaries of several transgenic lines overexpressing the SlyMIR159 were similar to those of the control. Moreover, our experiments suggested that auxin and GA may act repressing the miR159 node during fruit set initiation, in order to release the miR167-targeted SlyARF8A expression during fruit set. Our data show how two microRNA nodes (miR159 and miR167) integrated with hormone signalling into a circuit that coordinates successive steps along ovary and fruit development.

Mon laboratoire d’accueil a participé à l’identification du gène R-spondin1, dont les mutations sont responsables d’anomalies cutanées telles que l’hyperkératose palmo-plantaire, les prédispositions aux cancers spinocellulaires et certains types d’inversions de sexe. La génération du modèle murin a permis de montrer que RSPO1, un activateur de la voie de signalisation Wnt/ßcatenin, est nécessaire à la différenciation ovarienne. R-spondin1 et Sox9 sont connus comme étant des facteurs clé de la détermination du sexe femelle et mâle respectivement. J’ai tout d’abord participé à l’étude de leur fonction dans les pathologies d’inversions de sexe afin de déterminer le rôle de chacune de ces voies dans ces processus. L’étude de 2 modèles murins, d’invalidation conditionnelle du gène Sox9, ainsi que de double invalidation des gènes Sox9 et R-spondin1, a permis de montrer que la détermination du sexe est une balance entre la voie de signalisation mâle activée par les Sox et la voie de signalisation femelle activée par R-spondin1. Dans la 2ème partie de ma thèse j’ai évalué le rôle de R-spondin1 dans la physiologie de l’ovaire post-natal en étudiant un modèle murin de gain-de-fonction de R-spondin1 dans l’ovaire, puisque celui-ci est normalement faiblement exprimé au stade adulte. Cette partie de l ‘étude a démontré que le maintien de l'expression de R-spondin1 empêche les cellules nourricières de l’ovaire, les cellules de la granulosa, de se différencier, empêche l'atrésie folliculaire et favorise l’apparition de kystes sanguins après ovulation. / Our lab has contributed to the identification of the R-spondin1 (Rspo1) gene. Disruption of this gene leads to different defects such as palmoplantar hyperkeratosis, predisposition to squamous cell carcinoma and sex reversals. Establishment of the mouse model led to the result that RSPO1, which activates the WNT/ßcatenin signaling pathway, is necessary for ovarian differentiation. Rspo1 and Sox9 are known to be key factors in female and male sex determination, respectively. I first participated to the study of their role in sex reversals, in order to determine the role of each pathway in these processes. The study of 2 different mouse models (conditional knockout of Sox9 and R-spondin1/Sox9 double knockout), led us to the conclusion that sex determination is a balance between the male pathway activated by Sox genes and the female pathway activated by R-spondin1. I then evaluated the role of R-spondin1 in the adult ovary using a mouse model over expressing R-spondin1 in the ovary, as it is usually downregulated in the adult. I was able to observe that maintenance of R-spondin1 expression in the adult keeps the granulosa cell lineage from differentiating properly, prevents atresia in the ovary and may contribute to the formation of blood filled cysts following ovulation. In conclusion, our study shows that sex determination and adult ovary homeostasis need to be highly regulated. Deregulation of key genes such as R-spondin1 can lead to different pathologies, such as sex reversal and tumor formation.

Orientador: Wilter Ricardo Russiano Vicente / Banca: Luiz Fernando de Souza Rodrigues / Banca: César Roberto Esper / Resumo: Avaliou-se macro e microscopicamente os ovários de ovelhas submetidas a sucessivas aspirações foliculares, com o objetivo de se verificar se houve ou não interferência na produção oocitária e morfologia das gônadas; além da avaliação macroscópica do trato genital interno. Dezoito ovelhas da raça Santa Inês, distribuídas aleatoriamente compuseram três grupos experimentais de igual número (n=6). G0, G1, G9 com 0, 1 e 9 repetições, respectivamente. A sincronização do estro foi feita utilizando-se protocolo curto com MAP, seguindo-se estimulação, em dose única, com 80mg de FSHp e 300 UI de eCG (IM) e após 36 horas realizavam-se as aspirações foliculares por vídeolaparoscopia, com intervalo de 7 dias. Os folículos visibilizados, os aspirados e os oócitos recuperados foram contabilizados. Após a última intervenção foi realizada ovariectomia para avaliar os macro e microscopicamente, a existência ou não de lesões causadas pelas punções foliculares, classificando a intensidade do processo em ausente (0), leve (1), moderada (2) e severa (3). Os dados foram expressos em média e desvio padrão, comparados pelo teste one-way ANOVA e teste de Tukey. Os números de folículos visibilizados, aspirados e oócitos recuperados foram de 13,24±2,0, 11,27±3,03 e 5,79±2,3 respectivamente, com taxa de recuperação de 51,69%, não havendo diferenças entre as nove sessões (p>0,05). Também não se verificou, macroscopicamnte, lesões no trato genital interno, nem alterações consideráveis nas análises histológicas, sendo o escore 0±0 para o G0, 0,1±0,4 para o G1 e 0±0 para o G9 (p>0,05). Conclui-se que as nove sessões de superovulação e aspiração folicular não causam lesões ovarianas e não interferiram na produção de folículos em ovelhas da raça Santa Inês / Abstract: We evaluated macroscopically and microscopically the ovaries of ewes to repeated follicular aspiration, in order to verify whether or not there was interference with the production oocyte and gonad morphology, besides the macroscopic evaluation of internal genital tract. Eighteen sheep Santa Ines, randomly distributed three groups composed of equal numbers (n = 6). G0, G1, G9 with 0, 1 and 9 replicates, respectively. Synchronization of estrus was performed using short protocol with MAP, followed by stimulation in a single dose of 80mg FSHp and 300 IU of eCG (IM) and after 36 hours was held at the follicular aspiration by laparoscopy with interval 7 days. The follicles visualized, aspirated and the oocytes recovered were counted. After the last intervention was performed ovariectomy was performed to assess the macro and microscopically, the presence or absence of lesions caused by follicular puncture, classifying the intensity of the process as absent (0), mild (1), moderate (2) and severe (3) . Data were expressed as mean and standard deviation and compared by using one-way ANOVA and Tukey test. The numbers of follicles visualized, aspirated and oocytes recovered were 13.24 ± 2.0, 11.27 ± 3.03 and 5.79 ± 2.3 respectively, with a recovery rate of 51.69%, with no differences among the nine sessions (p> 0.05). Nor is there, macroscopicamnte, internal genital tract injury, or significant changes in histological evaluations, with a score of 0 ± 0 for G0, 0.1 ± 0.4 for G1 and 0 ± 0 for the G9 (p> 0.05). We conclude the nine sessions of superovulation and ovum do not cause ovarian lesions and did not interfere in the production of follicles in Santa Ines sheep / Mestre

L’objectif de cette thèse était d’identifier une mutation nommée FecLL affectant le nombre d’ovulations et la prolificité des brebis de race Lacaune et d’en analyser les conséquences physiologiques. En associant des approches de génétique et de biologie fonctionnelle à haut débit telles que le séquençage Roche 454 et la spectrométrie de masse, j’ai mis en évidence que la mutation FecLL est un haplotype de 2 SNPs présents dans des régions non-codantes d’un locus de 194,6kb porté par le chromosome 11 ovin. Cette mutation induit la surexpression ovarienne et l’activité du gène B4GALNT2 (beta-1,4-N-acetyl-galactosaminyl transferase 2) codant une enzyme de glycosylation capable de transférer un sucre N-acétyl-galactosamine sur des glycoprotéines cibles, dont l’inhibine A, une hormone importante pour la fonction ovarienne. Les conséquences de cette glycosylation atypique sont une altération de la production d’inhibine A chez les brebis Lacaune mutées, proposée comme mécanisme initiateur de leur hyper-prolificité. / The aim of this thesis was to identify a mutation called FecLL affecting ovulation rate and prolificacy of Lacaune sheep and to study its physiological consequences. By combining genetics and functional highthroughput biology approaches such as Roche 454 sequencing and mass spectrometry, I evidenced the FecLL mutation as a 2 SNP haplotype present in non-coding regions of a 194.6 kb locus on ovine chromosome 11. This mutation induces ectopic overexpression and ovarian activity of the B4GALNT2 (beta-1,4-N-acetylgalactosaminyl transferase 2) gene encoding a glycosylation enzyme capable of transferring a N-acetylgalactosamine sugar on target glycoproteins. Among those targets, I highlighted inhibin A, an important hormone in ovarian function. The consequences of this atypical glycosylation lead to impaired production of inhibin A in Lacaune mutated sheep proposed as an initiator mechanism of their hyper- prolificacy.