Orientador: Cesar Roberto Esper / Banca: Vênicio José de Andrade / Banca: Marcos Silva / Banca: Joaquim Mansano Garcia / Banca: Vera Fernanda Martins Hossipian de Lima / Resumo: Pouco se sabe sobre os eventos morfológicos que ocorrem durante o desenvolvimento pré-natal das gônadas nas raças zebuinas. O objetivo deste estudo foi descrever os eventos morfológicos relacionados ao desenvolvimento pré-natal da gônada, incluindo a sua formação, identificação de células germinativas primordiais, surgimento de oogônios, oócitos e folículos em embriões e fetos da raça Nelore. Oitenta e um embriões e fetos bovinos, com idade variando de 26 a 240 dias após fecundação, foram coletados em frigoríficos. A idade dos fetos foi estimada a partir de medidas tomadas no sentido crânio-caudal e aplicadas à fórmula proposta por Rexroad et. al. (1974). O sexo foi identificado a partir de observações macroscópicas e usando a técnica do PCR (Polymerase Chain Reaction) somente quando as diferenças sexuais morfológicas não foram evidentes. Para histologia, as gônadas foram fixadas em líquido de Bouin por 24 horas. Após processamento histológico, cortes de tecido de 5mm, foram corados com hematoxilina-eosina. Os resultados mostraram que a crista gonádica se formou a partir de 29 dias após fecundação. No 34º dia, células germinativas primordiais foram identificadas. As oogônias surgiram em grande quantidade entre 50 e 100 dias e seu número reduziu drasticamente, atingindo números finais aos 140 dias. Os folículos primordiais, folículos em crescimento e antrais apareceram em média aos 95, 140 e 180 dias, respectivamente. Oogônias e folículos primordiais, de forma diferente dos folículos em crescimento, apresentaram diferenças significativas no seu diâmetro nos vários períodos estudados. Folículos antrais mostraram diâmetro médio de 96,92 l 31,07mm aos 180 dias , chegando atingir médias de1331,43 l 567,43mm aos 240 dias... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Little is known about morphological events occurring during the prenatal development of gonads in the Zebu breeds. The objective of this study was to describe the morphologic events related to the prenatal development of the gonad, including its formation, identification of primordial germinative cells, appearance of oogonia, oocytes and follicles in Nelore breed embryos and fetuses. Eighty-one bovine embryos and fetuses, with age range from 26 to 240 days following fecundation, were gathered in a local slaughter-house. The age of fetuses was estimated from measures taken in the cranium-caudal direction and applied to the formula proposed by Rexroad et. al. (1974). The sex was identified from macroscopic observations and using PCR (Polymerase Chain Reaction) technique only when the morphologic sexual differences were not evident. For histology, gonads were fixed into Bouin fluid for 24 hours. Then, 5mm-tissue cuts were stained with hematoxylin-eosin. The results showed that the gonadal ridge was developed from 29 days following fecundation. At the 34th day, primordial germ cells were identified. Oogonia arose in great quantity between 50 and 100 days and its number reduced dramatically, attaining final numbers at 140 days. The primordial follicles, growing follicles and antral follicles appeared on the average at 95, 140 and 180 days, respectively. Oogonia and primordial follicles, in a different way from growing follicles, presented significant differences in its diameter in the several periods studied. Antral follicles showed 96.92 l 31.07mm in diameter at 180 days, achieving means of 1331.43 l 567.43 mm at 240 days. The statistical analysis showed a positive and highly significant correlation (P< 0.01), between the oogonia diameter and its nucleus, as well as between the primordial and growing follicles with its oocytes and respective nuclei... (Complete abstract, access undermentioned eletronic address) / Doutor

Os esteróides anabólicos-androgênicos (EAA) se caracterizam como um grupo de compostos naturais e sintéticos formados a partir da testosterona e seus derivados e foram desenvolvidos com finalidade terapêutica. No entanto, a partir da década de 90 o seu uso tem sido considerado um problema de saúde pública; e o seu consumo aumentado entre atletas profissionais e amadores que usam a medicação até 100 vezes acima da dose recomendada. Os efeitos adversos mais comuns relacionados ao uso dos EAA são alterações hepáticas, endócrinas, músculo-esqueléticas, cardiovasculares, imunológicas, reprodutivas, psicológicas, efeitos virilizantes e feminilizantes; e efeitos tóxicos. Apesar de diversos efeitos deletérios, os EAA em dose e freqüência adequada podem ter efeitos benéficos no reparo de feridas, revertendo os efeitos de corticosteróides. O objetivo deste trabalho foi avaliar os efeitos de doses suprafisiológicas (10mg/semana, por 60 dias) do EAA decanoato de nandrolona em 32 ratos (Rattus norvegicus), sendo divididos igualmente para o grupo experimental e controle (8 fêmeas e 8 machos para cada grupo) através da macroscopia, microscopia e morfometria. Os resultadosmostraram que os animais do grupo controle ganharam mais peso ao final do tratamento do que os animais tratados. Os ovários e testículos apresentaram atrofiaenquanto a hipertrofia foi observada nos úteros e próstatas, com diferença de peso significativa estatisticamente em todos os órgãos entre o grupo experimental e controle. Nos testículos, a contagem do número de células de Sertoli não apresentou diferença estatística, assim como no percentual de fibras colágenas entre o grupo experimental e controle. A média da altura das células epiteliais nas próstatas dos animais tratados apresentou-se maior que as do controle. Os ovários das ratas medicadas apresentaram diminuição de corpos lúteos e folículos atrésicos. Os resultados encontrados indicam que as altas doses do EAA decanoato de nandrolona causam alterações macroscópicas e morfológicas nos sistemas reprodutores de machos e fêmeas, podendo ser irreversíveis. O efeito benéfico do uso de EAA na síntese de colágeno não foi observado nos fragmentos de gengiva analisados. / The anabolic-androgenic steroids (AAS) are characterized as a group of natural and synthetic compounds formed from testosterone and derivatives, and have been developed for therapeutic purposes. However, after the 1990s, their utilization has been considered a public health problem and the intake increased among professional and amateur athletes, who ingest up to 100 times the recommended dose of the drug. The most common adverse effects related to utilization of AAS are hepatic, endocrine, muscle-skeletal, cardiovascular, immunological, reproductive and psychological alterations; masculinizing and feminizing effects; and toxic effects. Despite the several harmful effects, utilization of AAS at adequate dose and frequency may have beneficial effects on wound repair, reverting the effects of corticosteroids. This study evaluated the effects of supraphysiological doses (10mg/week, for 60 days) of the AAS nandrolone decanoate in 32 rats (Rattus norvegicus), equally divided into experimental and control groups (8 females and 8 males for each group), by macroscopic, microscopic and morphometric analyses. The results revealed that animals in the control group gained more weight at treatment completion than treated animals. The ovaries and testicles presented atrophy, and hypertrophy of uterus and prostates was observed, with statistically significant difference in weight in all organs between the experimental and control groups. In the testicles, counting of the number of Sertoli cells and the percentage of collagen fibers did not present statistically significant difference between the experimental and control groups. The mean height of epithelial cells in the prostates of treated animals was greater in treated animals than in the control group. The ovaries of treated rats exhibited reduction in corpora lutea and atresic follicles. The results indicated that high doses of AAS nandrolone decanoate caused macroscopic and morphological alterations in the reproductive systems of males and females, which may be irreversible. The beneficial effect of utilization of AAS on the collagen synthesis was not observed on gingival fragments analyzed

Finally, as the first step to study the regulation of Kit system, we found that IGF-I was a potent regulatory factor that up-regulated the expression of kitlga in zebrafish follicle cells. The stimulation involved transcription but not translation, indicating that the kitlga gene is a direct downstream target of IGF-I. The effect of IGF-I on kitlga was exerted via PI3K-Akt but not MAPK pathway. In contrast, the MAPK pathway may play a negative role in controlling kitlga expression. / Kit ligand (also named stem cell factor, SCF) is a pleiotropic growth factor with diverse biological functions. It exerts effects on target cells by binding to its cognate tyrosine kinase receptor, Kit. In mammals, accumulated evidence has demonstrated important roles for Kit ligand and Kit in gametogenesis, melanogenesis and haematopoiesis. However, very little is known about Kit system in other vertebrates. In the present study, we used zebrafish as the model to investigate the expression, regulation and function of the Kit system in the ovary. / On the other hand, cAMP is involved in regulating the expression of kitlga in zebrafish follicle cells. Two cAMP-activated effectors, PKA and Epac, have reverse effects. PKA promotes but Epac inhibits the expression of kitlga, which was identified by the respective activator. The effect of forskolin and H89 on IGF-I-induced expression of kitlga suggests a cross-talk between the two signaling pathways. Both hCG and PACAP inhibited IGF-I-induced kitlga expression, indicating that they may have negative regulation through cAMP signaling pathways in the full-grown follicles. (Abstract shortened by UMI.) / The zebrafish has two homologues of Kit ligand (kitlga and kitlgb) and Kit (kita and kitb ) instead of one copy for each as in mammals. The present study proposed the origin of these homologues in the zebrafish by phylogenetic and chromosome synteny analyses, and provided further evidence for neo- or subfunctionalization for both Kit ligands and Kit receptors in the zebrafish ovary. All four Kit system members exhibited distinct and significant changes in mRNA expression during folliculogenesis, particularly in the periovulatory period before and after final oocyte maturation and ovulation. / Then we further studied the spatial localization of each member within the follicle. The present study demonstrated that kitlga and kitb are exclusively expressed in the follicle layer, while kitlgb and kita only in the oocyte. Using CHO cell line as a bioreactor, we produced recombinant zebrafish Kitlga and Kitlgb. Analysis in mammalian COS-1 cells and zebrafish primary follicle cells confirmed their biological activity and binding specifity. Two opposite paracrine pathways of Kit system in the zebrafish ovary have been shown. Kitlga from the follicle cells preferably activates Kita in the oocyte in spite of the weak response of Kitb to it. Kitlgb from the oocyte, however, exclusively activates Kitb in the follicle cells without any effects on Kita. / Yao, Kai. / Adviser: Ge Wei. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 136-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Apesar dos inúmeros grupos de pesquisa de todo o mundo investigando o câncer, esta doença tem se ampliado significativamente. No caso do câncer de ovário, a despeito dos notáveis avanços observados nos tratamentos atuais, um desafio persiste: a incapacidade da preservação de oócitos em tratamento com quimioterapia, radioterapia e/ou cirurgia, nos quais são freqüentes os efeitos colaterais tais como a perda folicular, a infertilidade, a menopausa precoce e as falências ovarianas pós-quimioterapia, decorrentes da irradiação e pós-cirurgia. Neste sentido, o transplante de tecido ovariano pode representar uma alternativa na recuperação da capacidade fértil da mulher, bem como uma terapia de reposição hormonal após tratamento. No presente estudo, foram utilizadas linhagens de camundongos para avaliar a viabilidade do transplante ovariano antes e após a irradiação, como alternativa para a restauração das funções reprodutivas. Para tanto, fêmeas das linhagens isogênicas C57BL/6/Unib e híbridas B6CF1/Unib, foram acasaladas com machos da linhagem C57BL/6/Unib, empregandose diferentes protocolos com fêmeas submetidas ou não aos efeitos da radiação gama de Co-60 nas doses de 4 Gy e 6 Gy. Os resultados demonstram que a transferência ovariana restabeleceu a capacidade reprodutiva dos animais para níveis muito próximos dos normais; que o tamanho médio da ninhada, não revelou diferenças significativas após a transferência ovariana; que os fragmentos do ovário da receptora permanecem funcionais em períodos próximos pós à irradiação com 4 Gy e 6 Gy e que a irradiação nas doses de 4 Gy e 6 Gy destroem as células germinativas comprometendo a reprodução. / Despite numerous research groups, around the world, investigating the cancer, the disease has expanded significantly. In the case of the ovarian cancer, in spite of the notable advances seen in current treatments, a challenge remains: the incapacity to cryopreserve the oocyte in cancer chemotherapy, radiotherapy or surgery, in which side effects are frequent such as follicular loss, infertility, early menopause and ovarian bankruptcy after chemotherapy, after irradiation and post-surgery. In this regard, the transplant of ovarian tissues may be an alternative in recovering the women fertility, as well a hormone replacement therapy after treatment. In our study, we used inbred strains and hybrid mice to assess the viability of ovarian transplantation before and after irradiation, as an alternative for the restoration of the reproductive functions. For that female from the C57BL/6/Unib inbred strain and from the hybrid, B6C-F1/Unib mated with C57BL/6/Unib males, employing different protocols with irradiated and non irradiated females with doses of 4 Gy and 6 Gy of Co60 gamma radiation. The results demonstrate that the ovarian transfer restored the reproductive capacity of the females to almost the normal levels; that the litter size average (production index) showed no significant differences after the ovarian transfer; that the fragments from the ovary of the recipient female are functional in periods coming after irradiation with 4 Gy and 6 Gy and that the irradiation with 4 Gy and 6 Gy destroys the germ cells, compromising the reproduction.

Os esteróides anabólicos-androgênicos (EAA) se caracterizam como um grupo de compostos naturais e sintéticos formados a partir da testosterona e seus derivados e foram desenvolvidos com finalidade terapêutica. No entanto, a partir da década de 90 o seu uso tem sido considerado um problema de saúde pública; e o seu consumo aumentado entre atletas profissionais e amadores que usam a medicação até 100 vezes acima da dose recomendada. Os efeitos adversos mais comuns relacionados ao uso dos EAA são alterações hepáticas, endócrinas, músculo-esqueléticas, cardiovasculares, imunológicas, reprodutivas, psicológicas, efeitos virilizantes e feminilizantes; e efeitos tóxicos. Apesar de diversos efeitos deletérios, os EAA em dose e freqüência adequada podem ter efeitos benéficos no reparo de feridas, revertendo os efeitos de corticosteróides. O objetivo deste trabalho foi avaliar os efeitos de doses suprafisiológicas (10mg/semana, por 60 dias) do EAA decanoato de nandrolona em 32 ratos (Rattus norvegicus), sendo divididos igualmente para o grupo experimental e controle (8 fêmeas e 8 machos para cada grupo) através da macroscopia, microscopia e morfometria. Os resultadosmostraram que os animais do grupo controle ganharam mais peso ao final do tratamento do que os animais tratados. Os ovários e testículos apresentaram atrofiaenquanto a hipertrofia foi observada nos úteros e próstatas, com diferença de peso significativa estatisticamente em todos os órgãos entre o grupo experimental e controle. Nos testículos, a contagem do número de células de Sertoli não apresentou diferença estatística, assim como no percentual de fibras colágenas entre o grupo experimental e controle. A média da altura das células epiteliais nas próstatas dos animais tratados apresentou-se maior que as do controle. Os ovários das ratas medicadas apresentaram diminuição de corpos lúteos e folículos atrésicos. Os resultados encontrados indicam que as altas doses do EAA decanoato de nandrolona causam alterações macroscópicas e morfológicas nos sistemas reprodutores de machos e fêmeas, podendo ser irreversíveis. O efeito benéfico do uso de EAA na síntese de colágeno não foi observado nos fragmentos de gengiva analisados. / The anabolic-androgenic steroids (AAS) are characterized as a group of natural and synthetic compounds formed from testosterone and derivatives, and have been developed for therapeutic purposes. However, after the 1990s, their utilization has been considered a public health problem and the intake increased among professional and amateur athletes, who ingest up to 100 times the recommended dose of the drug. The most common adverse effects related to utilization of AAS are hepatic, endocrine, muscle-skeletal, cardiovascular, immunological, reproductive and psychological alterations; masculinizing and feminizing effects; and toxic effects. Despite the several harmful effects, utilization of AAS at adequate dose and frequency may have beneficial effects on wound repair, reverting the effects of corticosteroids. This study evaluated the effects of supraphysiological doses (10mg/week, for 60 days) of the AAS nandrolone decanoate in 32 rats (Rattus norvegicus), equally divided into experimental and control groups (8 females and 8 males for each group), by macroscopic, microscopic and morphometric analyses. The results revealed that animals in the control group gained more weight at treatment completion than treated animals. The ovaries and testicles presented atrophy, and hypertrophy of uterus and prostates was observed, with statistically significant difference in weight in all organs between the experimental and control groups. In the testicles, counting of the number of Sertoli cells and the percentage of collagen fibers did not present statistically significant difference between the experimental and control groups. The mean height of epithelial cells in the prostates of treated animals was greater in treated animals than in the control group. The ovaries of treated rats exhibited reduction in corpora lutea and atresic follicles. The results indicated that high doses of AAS nandrolone decanoate caused macroscopic and morphological alterations in the reproductive systems of males and females, which may be irreversible. The beneficial effect of utilization of AAS on the collagen synthesis was not observed on gingival fragments analyzed

Apesar dos inúmeros grupos de pesquisa de todo o mundo investigando o câncer, esta doença tem se ampliado significativamente. No caso do câncer de ovário, a despeito dos notáveis avanços observados nos tratamentos atuais, um desafio persiste: a incapacidade da preservação de oócitos em tratamento com quimioterapia, radioterapia e/ou cirurgia, nos quais são freqüentes os efeitos colaterais tais como a perda folicular, a infertilidade, a menopausa precoce e as falências ovarianas pós-quimioterapia, decorrentes da irradiação e pós-cirurgia. Neste sentido, o transplante de tecido ovariano pode representar uma alternativa na recuperação da capacidade fértil da mulher, bem como uma terapia de reposição hormonal após tratamento. No presente estudo, foram utilizadas linhagens de camundongos para avaliar a viabilidade do transplante ovariano antes e após a irradiação, como alternativa para a restauração das funções reprodutivas. Para tanto, fêmeas das linhagens isogênicas C57BL/6/Unib e híbridas B6CF1/Unib, foram acasaladas com machos da linhagem C57BL/6/Unib, empregandose diferentes protocolos com fêmeas submetidas ou não aos efeitos da radiação gama de Co-60 nas doses de 4 Gy e 6 Gy. Os resultados demonstram que a transferência ovariana restabeleceu a capacidade reprodutiva dos animais para níveis muito próximos dos normais; que o tamanho médio da ninhada, não revelou diferenças significativas após a transferência ovariana; que os fragmentos do ovário da receptora permanecem funcionais em períodos próximos pós à irradiação com 4 Gy e 6 Gy e que a irradiação nas doses de 4 Gy e 6 Gy destroem as células germinativas comprometendo a reprodução. / Despite numerous research groups, around the world, investigating the cancer, the disease has expanded significantly. In the case of the ovarian cancer, in spite of the notable advances seen in current treatments, a challenge remains: the incapacity to cryopreserve the oocyte in cancer chemotherapy, radiotherapy or surgery, in which side effects are frequent such as follicular loss, infertility, early menopause and ovarian bankruptcy after chemotherapy, after irradiation and post-surgery. In this regard, the transplant of ovarian tissues may be an alternative in recovering the women fertility, as well a hormone replacement therapy after treatment. In our study, we used inbred strains and hybrid mice to assess the viability of ovarian transplantation before and after irradiation, as an alternative for the restoration of the reproductive functions. For that female from the C57BL/6/Unib inbred strain and from the hybrid, B6C-F1/Unib mated with C57BL/6/Unib males, employing different protocols with irradiated and non irradiated females with doses of 4 Gy and 6 Gy of Co60 gamma radiation. The results demonstrate that the ovarian transfer restored the reproductive capacity of the females to almost the normal levels; that the litter size average (production index) showed no significant differences after the ovarian transfer; that the fragments from the ovary of the recipient female are functional in periods coming after irradiation with 4 Gy and 6 Gy and that the irradiation with 4 Gy and 6 Gy destroys the germ cells, compromising the reproduction.

This experiment was designed to determine the involvement of varying levels of whole-body irradiation on ovarian follicular and corpora luteal development in mice. Previous research has indicated reduced counts of ovarian follicles and corpora lutea in mice flown in space. These differences may be the result of microgravity, increased exposure to radiation, or some combination of both. Fifty-six mice were divided into three groups (apocynin-treated, nox2 knockout, and wild-type control) before exposure to 0 Gy, 0.5 Gy, or 2.0 Gy radiation. The tissues were harvested, preserved, run through the appropriate paraffin embedding procedures, serially sectioned, mounted on microscope slides, and stained using a standard H&E staining technique. Total and mean follicular and corpora luteal counts were accessed and compared across treatment groups. Mean ovarian weight, mean total reproductive weight, mean ovarian weight percentage of total body weight, mean total reproductive weight percentage of total body weight, and the apparent estrous phase of the animals were also compared. Radiation from 0.5-2.0 Gy had no significant effect on mean ovarian weight, mean total reproductive weight, mean ovarian weight percentage of total body weight, or mean total reproductive weight percentage of total body weight. Radiation from 0.5-2.0 Gy significantly increased mean early-stage follicular count in the wildtype group only. Radiation of 2.0 Gy increased late-stage follicular count across all groups after accounting for mean ovarian percent of total body weight. Radiation of 2.0 Gy significantly increased mean corpora lutea count in the wildtype group only. This result not only suggests that low-dose radiation accelerates oocyte development in the murine ovary, but also that the inaction of NADPH-oxidase (via apocynin inhibition or genetic knockout) may ameliorate some of these effects.

Abstract not available

Bibliography: p. 159-193. / x, 200 p. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis compares the rates of mitotic activity of the ovarian surface epithelium (OSE) and the peritoneal mesothelium (PM) and the effects of ovarian hyperstimulation using a rodent model. The study provides also information about cytokine expression and production in benign and malignant ovarian tissue, both in humans and animals. / Thesis (M.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1997?

Thesis (Ph. D.)--West Virginia University, 2006. / Title from document title page. Document formatted into pages; contains vi, 156 p. : ill. (some col.). Includes abstract. Includes bibliographical references.