Os Galea spixii são roedores que tem despertado o interesse de pesquisadores devido ao seu peculiar dimorfismo sexual, uma vez que, as fêmeas possuem a genitália externa com características masculinizadas. O objetivo da presente pesquisa foi estabelecer os parâmetros morfológicos do desenvolvimento e diferenciação sexual de machos e fêmeas durante o período intrauterino e as possíveis fontes de produção de hormônios andrógenos e estrógenos durante a gestação. Foram utilizados conceptos provenientes de 30 fêmeas gestantes. Foi descrita a concentração hormonal das gestantes. Em seguida, os órgãos genitais dos conceptos foram analisados macroscopicamente e microscopicamente. E, para detectar possíveis fontes de andrógenos e estrógenos, as placentas, ovários e testículos foram submetidos a técnicas imunológicas de detecção de enzimas esteroidogênicas. Aos 25 dias de gestação (DG) se inicia o processo de diferenciação sexual das gônadas (para formar os ovários ou os testículos) e da genitália externa. O tubérculo genital sofre a canalização da uretra aos 30 DG para formar o pênis nos machos e aos 40 DG para formar o clitóris das fêmeas. Nos machos, a partir dos ductos mesonéfricos, se diferenciam os ductos epididimários e os ductos deferentes. Nas fêmeas, os ductos paramesonéfricos formam as tubas e cornos uterinos, o útero parcialmente duplo e a porção cranial da vagina. A porção caudal se origina do seio urogenital e a membrana de oclusão vaginal, da membrana urogenital. Também ficou demonstrado que, a concentração de testosterona sofre grande aumento, dos 25 DG até o final da gestação e que o mesmo não ocorre com o estradiol. Os resultados para detecção de enzimas esteroidogênicas sugerem que, a placenta pode ser o órgão que atua na produção de hormônios andrógenos e pode não realizar a conversão desses hormônios em estrógenos, devido à ausência da enzima responsável por este processo. Por fim, os testículos e ovários também podem contribuir com a produção dos principais andrógenos e o ovário também possui a enzima necessária para a produção de estrógenos. / Galea spixii are rodents that have aroused the interest of researchers because of their peculiar sexual dimorphism, since females have the external genitalia with masculinized characteristics. The aim of the present research was to establish the morphological parameters of the development and sexual differentiation of males and females during the intrauterine period and the possible sources of androgen and estrogen hormones production during pregnancy. Concepts from 30 pregnant females were used. The hormonal concentrations of pregnant were described. Then, the genital organs of the concepts were analyzed macroscopically and microscopically. And, to detect possible sources of androgens and estrogens, placentas, ovaries and testes were subjected to immunological techniques for the detection of steroidogenic enzymes. At 25 days of gestation (DG) the process of sexual differentiation of the gonads (to form the ovaries or testicles) and the external genitalia begins. The genital tubercle undergoes channeling of the urethra at 30 DG to form the penis in males and at 40 DG to form the clitoris of females. In males, the epididymal ducts and the vas deferens differentiate from the mesonephric ducts. In females, the paramesonephric ducts form the uterine tubes and horns, the partially double uterus and the cranial portion of the vagina. The caudal portion originates from the urogenital sinus and the vaginal closure membrane originates from the urogenital membrane. It has also been shown that the testosterone concentration is greatly increased from 25 DG until the end of gestation and that the same does not occur with estradiol. The results for the detection of steroidogenic enzymes suggest that the placenta may be the organ that acts in the production of androgen hormones and may not perform the conversion of these hormones into estrogens due to the absence of the enzyme responsible for this process. Finally, the testicles and ovaries can also contribute to the production of the main androgens and the ovary also has the enzyme necessary for the production of estrogens.

Os Galea spixii são roedores que tem despertado o interesse de pesquisadores devido ao seu peculiar dimorfismo sexual, uma vez que, as fêmeas possuem a genitália externa com características masculinizadas. O objetivo da presente pesquisa foi estabelecer os parâmetros morfológicos do desenvolvimento e diferenciação sexual de machos e fêmeas durante o período intrauterino e as possíveis fontes de produção de hormônios andrógenos e estrógenos durante a gestação. Foram utilizados conceptos provenientes de 30 fêmeas gestantes. Foi descrita a concentração hormonal das gestantes. Em seguida, os órgãos genitais dos conceptos foram analisados macroscopicamente e microscopicamente. E, para detectar possíveis fontes de andrógenos e estrógenos, as placentas, ovários e testículos foram submetidos a técnicas imunológicas de detecção de enzimas esteroidogênicas. Aos 25 dias de gestação (DG) se inicia o processo de diferenciação sexual das gônadas (para formar os ovários ou os testículos) e da genitália externa. O tubérculo genital sofre a canalização da uretra aos 30 DG para formar o pênis nos machos e aos 40 DG para formar o clitóris das fêmeas. Nos machos, a partir dos ductos mesonéfricos, se diferenciam os ductos epididimários e os ductos deferentes. Nas fêmeas, os ductos paramesonéfricos formam as tubas e cornos uterinos, o útero parcialmente duplo e a porção cranial da vagina. A porção caudal se origina do seio urogenital e a membrana de oclusão vaginal, da membrana urogenital. Também ficou demonstrado que, a concentração de testosterona sofre grande aumento, dos 25 DG até o final da gestação e que o mesmo não ocorre com o estradiol. Os resultados para detecção de enzimas esteroidogênicas sugerem que, a placenta pode ser o órgão que atua na produção de hormônios andrógenos e pode não realizar a conversão desses hormônios em estrógenos, devido à ausência da enzima responsável por este processo. Por fim, os testículos e ovários também podem contribuir com a produção dos principais andrógenos e o ovário também possui a enzima necessária para a produção de estrógenos. / Galea spixii are rodents that have aroused the interest of researchers because of their peculiar sexual dimorphism, since females have the external genitalia with masculinized characteristics. The aim of the present research was to establish the morphological parameters of the development and sexual differentiation of males and females during the intrauterine period and the possible sources of androgen and estrogen hormones production during pregnancy. Concepts from 30 pregnant females were used. The hormonal concentrations of pregnant were described. Then, the genital organs of the concepts were analyzed macroscopically and microscopically. And, to detect possible sources of androgens and estrogens, placentas, ovaries and testes were subjected to immunological techniques for the detection of steroidogenic enzymes. At 25 days of gestation (DG) the process of sexual differentiation of the gonads (to form the ovaries or testicles) and the external genitalia begins. The genital tubercle undergoes channeling of the urethra at 30 DG to form the penis in males and at 40 DG to form the clitoris of females. In males, the epididymal ducts and the vas deferens differentiate from the mesonephric ducts. In females, the paramesonephric ducts form the uterine tubes and horns, the partially double uterus and the cranial portion of the vagina. The caudal portion originates from the urogenital sinus and the vaginal closure membrane originates from the urogenital membrane. It has also been shown that the testosterone concentration is greatly increased from 25 DG until the end of gestation and that the same does not occur with estradiol. The results for the detection of steroidogenic enzymes suggest that the placenta may be the organ that acts in the production of androgen hormones and may not perform the conversion of these hormones into estrogens due to the absence of the enzyme responsible for this process. Finally, the testicles and ovaries can also contribute to the production of the main androgens and the ovary also has the enzyme necessary for the production of estrogens.

La tuberculose est due à un groupe d’agents infectieux phylogénétiquement proches formant le complexe Mycobacterium tuberculosis, formé de dix espèces. M. tuberculosis est un bacille à croissance lente qui forme des colonies rugueuses. Le complexe M. tuberculosis comporte également des bacilles tuberculeux formant des colonies lisses à croissance rapide, isolées qu’à partir de prélèvements cliniques chez l’homme. Notre revue des articles sur ces souches a montré que les trois premiers isolats ont été obtenus chez des patients en France, à Madagascar et en Polynésie Française par Georges Canetti entre 1968 et 1970. Suite à l'isolement d'une souche lisse à partir d’un ganglion cervical chez un enfant Somali de 2 ans en 1997, ces bacilles tuberculeux ont été nommés "Mycobacterium canettii". Aujourd'hui, moins d'une centaine de ces souches ont été isolées à partir de patients exposés aux pays formant la Corne de l’Afrique, principalement la République de Djibouti, qui présente la plus forte prévalence. Nous avons procédé à l’analyse génotypique de 34 isolats de M. tuberculosis et de 87 isolats de mycobactéries non-tuberculeuses de la Polynésie Française pour voir si des telles souches persistaient.Nous avons pu décrire deux nouvelles lignées de M. tuberculosis et une nouvelle espèce de mycobactérie non-tuberculeuse. Nous avons envisagé une transmission par voie digestive de "M. canettii" et nous avons testé la résistance de "M. canettii" à la chaleur. Nous avons observé la croissance de cette dernière entre 25°C et 45°C. Les données que nous avons obtenues ici pourraient former une base en vue d'élucider les réservoirs et les sources de souches lisses. / Tuberculosis is caused by a group of phylogenetically close infectious agents forming the Mycobacterium tuberculosis complex, consisting of ten species. M. tuberculosis is a slow growing bacterium which form rough colonies. The complex also includes M. tuberculosis tubercle bacilli forming smooth rapidly-growing colonies isolated from clinical specimens in humans. Our review of articles on these strains showed that the first three isolates were obtained from patients in France, Madagascar and French Polynesia by Georges Canetti between 1968 and 1970. Following the isolation of a smooth strain from cervical ganglion of a Somali 2 year-old child in 1997, the tubercle bacilli were named "Mycobacterium canettii". Today, less than a hundred of these strains were isolated from patients exposed to countries forming the Horn of Africa, especially the Republic of Djibouti, which has the highest prevalence. As showed in our revue, one smooth tubercle bacilli was isolated in Frenche Polynesia. To see if such strains persist there, we performed the genotyping of 34 isolates of M. tuberculosis and 87 isolates of non-tuberculous mycobacteria from French Polynesia. We have described two new strains of M. tuberculosis and a new species of mycobacterium tuberculosis not. We considered, on the basis of our data, a transmission through the digestive tract for "M. canettii" and we tested the resistance "Mr. canettii" to heat. We observed the growth of the latter between 25°C and 45°C. The data we got here could form a basis to elucidate the reservoirs and sources of smooth strains.

Chez l'homme comme chez l'animal, les odeurs guident le comportement et motivent à agir. La valeur hédonique (le caractère plus ou moins plaisant) est la dimension olfactive principale et est généralement utilisée pour décider d'approcher ou fuir la source odorante. Bien que cette attractivité soit façonnée par l'expérience, certaines odeurs non-familières sont spontanément attractives ou répulsives. Le caractère plus ou moins plaisant d'une odeur serait, du moins en partie, inné. Il existerait ainsi une signature neurale spécifique de la valeur hédonique des odeurs, et c'est ce que cette thèse s'emploie à identifier.Après sélection d'odorants spontanément plus ou moins attractifs (plaisant et déplaisants respectivement), nous avons recherché les bases neurales qui sous-tendent ces comportements. Nous avons tout d'abord cartographié (expression de Zif268) puis manipulé (optogénétique) l'activité neuronale du bulbe olfactif en réponse à ces odorants, et avons révélé une signature neurale bulbaire de la valeur hédonique des odeurs le long de l'axe antéro-postérieur.Puis, afin d'analyser comment le message hédonique était interprété par les aires olfactives et associatives supérieures, nous avons développé une méthode de recalage de l'activité cérébrale dans un atlas de référence, assurant une cartographie rapide, précise et fiable de cette activité. Enfin, en combinant cette méthode à des approches comportementales, électrophysiologiques et pharmacologiques, nous avons montré un rôle du système de la récompense dans le codage de la valeur hédonique des odeurs et qu'une odeur peut être perçue comme une récompense, motivant alors les comportements d'approche et de retrait / In humans and animals, odors guide behavior and motivate action. The hedonic value (that is the pleasantness) is the main olfactory dimension and is generally used to decide to approach the odor source or move away. While this attractiveness is shaped by experience, some unfamiliar odors are spontaneously attractive or repulsive. The pleasantness of an odor would be, at least in part, innate, and suggest a specific neural signature of the hedonic value of odors. The global aim of this thesis is to decipher neuronal mechanisms underlying the hedonic value of odors.After having selected odorants with various level of attraction (pleasant and unpleasant), we have deciphered the neural bases that underlie these behaviors.We first mapped (expression of Zif268) and then manipulated (optogenetic) the neuronal activity of the olfactory bulb in response to these odors, and have revealed a bulbar neural signature of the hedonic value of odors along the antero-posterior axis.Then, in order to analyze how the hedonic information was interpreted by the higher olfactory and associative areas, we developed a method allowing the registration of brain activity in a reference atlas, that ensure a fast, accurate and reliable mapping of this activity. Finally, by combining this method with behavioral, electrophysiological and pharmacological approaches, we have shown a role of the reward system in the coding of odor hedonics and that an odor can act as a reward, thus motivating behavior, approach and withdrawal

La tuberculose est l’une des maladies infectieuses mortelles les plus fréquentes, causée par des mycobactéries tuberculeuses dont principalement M. tuberculosis. Notre thèse a porté sur Mycobacterium canettii caractérisée par un morphotype lisse et un temps de génération plus court que M. tuberculosis. Notre revue de la littérature a montré que moins d'une centaine de cas d’infection à M. canettii ont été rapportés majoritairement à Djibouti située dans la Corne de l’Afrique. Ensuite, notre étude prospective de la tuberculose pulmonaire à Djibouti a mesuré une prévalence d’infections à M. canettii de 4%. A travers un modèle murin d’infection par gavage, nous avons observé la translocation de M. canettii des intestins vers la circulation lymphatique et sanguine ; suivie par une dissémination principalement vers les poumons et les ganglions lymphatiques. Cette étude a alors démontré que M. canettii peut infecter les individus par voie orale et a révélé que M. canettii peut interagir avec le tissu adipeux brun. Ensuite, à travers des modèles cellulaires d’infection, nous avons montré que les pré-adipocytes bruns pourraient constituer une cible potentielle des mycobactéries tuberculeuses et que M. canettii ne persiste pas dans les adipocytes matures contrairement à M. tuberculosis. En conclusion, nous avons apporté des connaissances nouvelles sur l’infection à M. canettii : sa prévalence, son mode de transmission ainsi que de nouvelles pistes sur de possibles réservoirs environnementaux. L’ensemble de ces données suggèrent que l’infection à M. canettii doit être considérée comme une entité clinique distincte de la tuberculose que nous proposons de nommer « Canettose ». / Tuberculosis is one of the most frequent deadly infectious diseases worldwide, caused by tuberculous mycobacteria including mainly M. tuberculosis. Our thesis focused on Mycobacterium canettii characterized by a smooth morphotype and a shorter generation time than M. tuberculosis. Our review of the literature showed that less than one hundred cases of M. canettii infection have been reported in Djibouti situated in the Horn of Africa. Then, our prospective microbiological study of pulmonary tuberculosis in Djibouti measured a prevalence of M. canettii lung infections of 4%. Through a mouse model by gavage, we observed the translocation of M. canettii from the intestines to the lymphatic and blood circulation; followed by dissemination mainly to the lungs and lymph nodes. In conclusion, this study demonstrated that M. canettii can follow the digestive tract to infect individuals and revealed also that M. canettii can interact with brown adipose tissue. Then, through cell infection models, we have shown that brown pre-adipocytes may be a potential target for tuberculous mycobacteria and that M. does not persist in mature adipocytes contrary to M. tuberculosis. In conclusion, this work allowed to bring new knowledge about M. canettii infection: its prevalence, its mode of transmission as well as new avenues on possible environmental reservoirs. All of these data suggest that M. canettii infection should be considered as a distinct clinical entity from tuberculosis. We propose to name "Canettosis" the M. canettii infection.