AGRADECIMENTOS Desejo agradecer aos meus orientadores Prof. Sergio e Prof a . Cintia, obrigada pela confiança, oportunidade e pelo imensurável aprendizado. Aos meus pais e família, obrigada por estimular desde sempre o espírito curioso e o contato com a ciência. As discussões sobre física e sobre o Universo foram essenciais na formação do meu espírito e caráter. Ao meu marido, obrigada pelo incentivo e incansáveis leituras e conversas sobre mitocôndrias e Biologia Molecular. Aos colegas do LIM

more »

... 0 e do Departamento de Medicina Legal, Ética Médica, Medicina Social e do Trabalho, obrigada pela paciência, pela ajuda, almoços e risadas durante todo esse período. Às amigas Nathalie, Mari e Felícia, obrigada por me ensinarem um mundo novo e por manterem minha janela sempre aberta. Aos amigos e colegas do Setor de Endometriose do Departamento de Ginecologia e Obstetrícia, obrigada pelo acolhimento e por permitir meu crescimento pessoal e acadêmico. Ginecologia e Obstetrícia, agradeço por toda a minha formação como médica e pesquisadora. ABSTRACT Andres MP. Polymorphisms of control region (D-loop) of mitochondrial DNA in Brazilian women with endometriosis [Dissertation]. São Paulo: "Faculdade de Medicina, Universidade de São Paulo"; 2017. Background: There is increasing evidence that oxidative stress is a major factor in the pathogenesis of endometriosis, a prevalent disease that affects 5-15% of reproductive-aged women worldwide. Polymorphisms in the control region of mitochondrial DNA (mtDNA) can lead to the altered replication and transcription of mitochondrial genes, thereby affecting both overall mitochondrial function, and the intracellular generation of reactive oxygen species. Objective: The present study investigated whether the incidence of mtDNA polymorphisms and/or haplogroups is associated with endometriosis in a Brazilian population. Methods: Female patients (aged 18-50 years) were enrolled in the present study, and assigned to either endometriosis (n = 90) or control (n = 92) group. The former group comprised patients who had received a histological diagnosis of endometriosis and had been assigned a surgical stage, while the latter comprised patients who had undergone gynecological surgery for tubal ligation, leiomyoma, or ovarian cysts, and showed no evidence of endometriosis. DNA was extracted from peripheral blood samples, and then subjected to Sanger sequencing and capillary electrophoresis. Polymorphisms were identified by comparing the isolated mtDNA sequences with the revised Cambridge Reference Sequence. Results: The frequency of some identified polymorphisms was found to be higher in the endometriosis group than in the control group, including polymorphisms T16217C (found in 14.4% and 5.4% of endometriosis-and control-group members, respectively; p=0.049), G499A (13.3% vs. 4.3%; p=0.038), T236C (5.6% vs. 0%; p=0.028), and G185A (6.7% vs. 0%; p=0.013). In contrast, polymorphisms T146C (18.9% vs. 32.6%; p=0.042) and 573.2C (5.6% vs. 29.3%; p<0.001) were found to occur at a lower frequency in the endometriosis compared to the control group. Observed haplogroup frequencies were similar between the endometriosis and control groups, and did not appear to be affected by either disease location and/or staging. Conclusion: mtDNA polymorphisms T16217C, G499A, T236C, and G185A were found to be associated with endometriosis, while conversely, T146C and 573.2C were shown to be associated with an absence of disease in the analyzed Brazilian population. No significant differences were observed between the mitochondrial haplogroups of patients with, versus without endometriosis.