The renal capsule is a flattened layer of cells which surround the kidney. Expression of the transcription factor Foxd1 is required for normal development of the capsule. Furthermore, current evidence suggests that during development the capsule progenitors are in a state of active hedgehog signaling. We hypothesize that hedgehog plays a role in modulating capsule morphogenesis in the embryonic kidney. To test the hypothesis hedgehog signaling was inhibited in the capsule via Foxd1Cre mediated deletion of Smoothened (Smo), the activator of the pathway. Mutant kidneys were approximately 48% smaller in volume and had a 42% decrease in nephron number. Furthermore, mutants displayed abnormal patterning of the capsule where regions on the surface of the kidney had no capsule cells. The discontinuous capsule phenotype was observed only after E13.5. Additionally, capsule cells progressively lost expression of known markers Foxd1 and Raldh2 and their proliferative capacity was decreased by 54% at E13.5.

The renal capsule is a flattened layer of cells which surround the kidney. Expression of the transcription factor Foxd1 is required for normal development of the capsule. Furthermore, current evidence suggests that during development the capsule progenitors are in a state of active hedgehog signaling. We hypothesize that hedgehog plays a role in modulating capsule morphogenesis in the embryonic kidney. To test the hypothesis hedgehog signaling was inhibited in the capsule via Foxd1Cre mediated deletion of Smoothened (Smo), the activator of the pathway. Mutant kidneys were approximately 48% smaller in volume and had a 42% decrease in nephron number. Furthermore, mutants displayed abnormal patterning of the capsule where regions on the surface of the kidney had no capsule cells. The discontinuous capsule phenotype was observed only after E13.5. Additionally, capsule cells progressively lost expression of known markers Foxd1 and Raldh2 and their proliferative capacity was decreased by 54% at E13.5.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13462号 / 論医博第2249号 / 新制||医||1055(附属図書館) / (主査)教授 萩原 正敏, 教授 松田 秀一, 教授 齊藤 博英 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Made available in DSpace on 2016-08-15T20:31:12Z (GMT). No. of bitstreams: 1 NayaraAC_DISSERT.pdf: 1401697 bytes, checksum: 483ad3e8e94846f136ca4ca2f701d984 (MD5) Previous issue date: 2013-08-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / At birth , domestic animals exhibit a large stock of oocytes which only a minimum reaches meiotic maturation. These oocytes contained in primordial follicles are used for the development of studies in order to clarify issues related to the activation of primordial follicles and growth as well as promote the development of new contraceptive methods and new techniques for the recovery of fertility through its cultivation. Among the ovarian culture stands out in vivo , also known as transplantation, has as main objectives to promote the return of fertility in women undergoing treatment gonadotoxic and the preservation of genetic diversity of endangered animals. In this sense the research with the in vivo culture aims to determine which methodology seems more feasible and allows better maintenance and development of the transplanted tissue. Thus , this study aimed to assess the quality of ovarian follicles after transplantation under the kidney capsule of mice. For this, we used 10 female mice ( Mus musculus ) , divided into two groups , Group 1 : transplants removed after 15 days from the insertion of the fragment , group 2 after 30 days. It has been established the control group which are the ovarian cortical fragments removed directly for histological processing. Through evaluation by light microscopy , it was observed that there was a progressive reduction in the number of morphological normal follicles with progression of duration to 15 for 30 days of transplants. Regarding the number of normal preantral, only group 2 did not differ statistically from the control. The normal antral follicles in groups 1 and 2 did not differ but were significantly lower than the control group. Regarding the evaluation of apoptotic, we obtained a higher reaction to Caspase -3 in antral follicles in the three groups. According to the results obtained in this study, subcapsular renal autotransplantation technique has proved satisfactory for maintenance and study of preantral follicles / Ao nascerem, os animais domésticos apresentam uma grande reserva de oócitos dos quais apenas um número mínimo atinge a maturação meiótica. Estes oócitos contidos em folículos pré-antrais são utilizados para o desenvolvimento de estudos com o intuito tanto de esclarecer questões relacionadas à ativação e crescimento de folículos primordiais quanto promover o desenvolvimento de novos métodos de contracepção e novas técnicas de recuperação da fertilidade através do seu cultivo. Dentre os tipos de cultivo ovariano destaca-se o in vivo, também conhecido por transplante, tem como principais objetivos promover o retorno da fertilidade em mulheres submetidas a tratamento gonadotóxico e a preservação da diversidade genética de animais ameaçados de extinção. Neste sentido, as pesquisas com o com cultivo in vivo, almejam determinar qual metodologia mostra-se mais viável e permite uma melhor manutenção e desenvolvimento do tecido transplantado. Desta forma, o presente estudo objetivou avaliar a qualidade dos folículos ovarianos após o autotransplante sob a cápsula renal de camundongas. Para isso, foram utilizadas 10 camundongas (Mus musculus), divididas em dois grupos, Grupo 1: remoção dos transplantes após 15 dias a partir da inserção do fragmento, grupo 2: após 30 dias. Ainda foi estabelecido o grupo controle que corresponde a fragmentos corticais removidos do ovário destinados diretamente para o processamento histológico. Através da avaliação por microscopia ótica, observou-se que houve uma redução no número de folículos morfologicamente normais com a progressão do tempo de duração dos transplantes de 15 para 30 dias. Com relação ao número folículos pré-antrais normais apenas o grupo 2 não diferiu estatisticamente do controle. Os folículos antrais normais dos grupos 1 e 2 não diferiram entre si mas apresentaram-se significativamente inferiores ao grupo controle. Quanto à avaliação da ocorrência de apoptose, obteve-se uma maior reação à Caspase-3 em folículos antrais nos três grupos. De acordo com os resultados obtidos no presente estudo, o autotransplante subcapsular renal demonstrou ser uma técnica satisfatória para manutenção e estudo de foliculos pré-antrais