Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina

Detalhes bibliográficos
Ano de defesa: 2016
Autor(a) principal: Costa, Felipe lattes
Orientador(a): Cruz, Ivana Beatrice Mânica da lattes
Banca de defesa: Fachinetto, Roselei lattes, Bresciani, Guilherme Bergamaschi lattes, Comim, Fabio Vasconcellos lattes, Sagrillo, Michele Rorato lattes
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Santa Maria
Centro de Ciências da Saúde
Programa de Pós-Graduação: Programa de Pós-Graduação em Farmacologia
Departamento: Farmacologia
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufsm.br/handle/1/18127
Resumo: Previous studies indicate that changes in oxidative metabolism may play a role in reproductive success. Manganese-dependent superoxide dismutase enzyme (SOD2), a key in the oxidative balance, presents a genetic variation Val16Ala-SOD2 that leads to a change in its efficiency causing an imbalance between the superoxide (S) and hydrogen peroxide (HP) levels of Cells. Studies have suggested that both homozygous genotypes (AA-VV) cause an S-HP imbalance associated with the risk of various chronic diseases, and interfere with female reproductive success. Thus, the objective of this work was to investigate the effect of the genetic imbalance caused by the polymorphism Val16Ala-SOD2 and pharmacological induced by the treatment with paraquat in oxidative metabolism and in male fertility indicators. For the in vitro analysis of the impact of the S-HP imbalance caused by the pharmacological action of paraquat, a method of quantification of the levels of cfDNA in the seminal plasma was conducted by fluorimetry using the DNA Picogreen. The second protocol investigated the association between the Val16Ala- SOD2 polymorphism with changes in the male fertility parameters determined by the WHO, by evaluating the association of this polymorphism with high levels of cfDNA and markers of oxidative stress in seminal plasma. Semen samples were obtained from healthy volunteers or from surplus samples used to perform sperm in laboratory clinical analyzes, the samples were processed and analyzed in the Biogenomic Laboratory, through spectrophotometric and molecular tests. The results showed a significant association between elevated levels of cfDNA and altered fertility parameters in semen, such as: low viability, changes in motility and sperm morphology. In vitro complementary analysis confirmed that high levels of S causes oxidative stress and decrease sperm viability. These results corroborated the hypothesis that cfDNA levels could be markers of general sperm quality and oxidative stress.
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spelling 2019-09-03T19:15:06Z2019-09-03T19:15:06Z2016-12-07http://repositorio.ufsm.br/handle/1/18127Previous studies indicate that changes in oxidative metabolism may play a role in reproductive success. Manganese-dependent superoxide dismutase enzyme (SOD2), a key in the oxidative balance, presents a genetic variation Val16Ala-SOD2 that leads to a change in its efficiency causing an imbalance between the superoxide (S) and hydrogen peroxide (HP) levels of Cells. Studies have suggested that both homozygous genotypes (AA-VV) cause an S-HP imbalance associated with the risk of various chronic diseases, and interfere with female reproductive success. Thus, the objective of this work was to investigate the effect of the genetic imbalance caused by the polymorphism Val16Ala-SOD2 and pharmacological induced by the treatment with paraquat in oxidative metabolism and in male fertility indicators. For the in vitro analysis of the impact of the S-HP imbalance caused by the pharmacological action of paraquat, a method of quantification of the levels of cfDNA in the seminal plasma was conducted by fluorimetry using the DNA Picogreen. The second protocol investigated the association between the Val16Ala- SOD2 polymorphism with changes in the male fertility parameters determined by the WHO, by evaluating the association of this polymorphism with high levels of cfDNA and markers of oxidative stress in seminal plasma. Semen samples were obtained from healthy volunteers or from surplus samples used to perform sperm in laboratory clinical analyzes, the samples were processed and analyzed in the Biogenomic Laboratory, through spectrophotometric and molecular tests. The results showed a significant association between elevated levels of cfDNA and altered fertility parameters in semen, such as: low viability, changes in motility and sperm morphology. In vitro complementary analysis confirmed that high levels of S causes oxidative stress and decrease sperm viability. These results corroborated the hypothesis that cfDNA levels could be markers of general sperm quality and oxidative stress.Estudos prévios indicam que alterações no metabolismo oxidativo podem atuar no sucesso reprodutivo. A enzima superóxido dismutase dependente de manganês (SOD2), chave no equilíbrio oxidativo, apresenta uma variação genética Val16Ala-SOD2 que leva a uma mudança na sua eficiência causando um desequilíbrio entre os níveis de superóxido (S) e peróxido de hidrogênio (HP) das células. Estudos sugeriram que os ambos genótipos homozigoticos (AA-VV) causam um desbalanço S – HP associado ao risco de diversas doenças crônicas, além de interferir no sucesso reprodutivo feminino. Assim, o objetivo desse trabalho foi investigar o efeito do desbalanço genético causado pelo polimorfismo Val16Ala-SOD2 e farmacológico induzido pelo tratamento com paraquat no metabolismo oxidativo e em indicadores de fertilidade masculina. Para a análise in vitro do impacto do desbalanço S- HP causado por ação farmacológica do paraquat, foi conduzida a validação de um método de quantificação dos níveis de cfDNA no plasma seminal através de fluorimetria utilizando o corante DNA Picogreen. O segundo protocolo investigou a associação entre o polimorfismo Val16Ala-SOD2 com alterações nos parâmetros de fertilidade masculina determinados pela OMS, através da avaliação da associação deste polimorfismo com níveis elevados de cfDNA e de marcadores de estresse oxidativo no plasma seminal. Amostras de sêmen foram obtidas de voluntários saudáveis ou de amostras excedentes utilizadas para a realização de espermograma em laboratório de análises clinicas, as amostras foram processadas e analisadas no Laboratório Biogenômica, através de testes espectrofotométricos e moleculares. O conjunto dos resultados demonstrou associação significativa entre níveis elevados de cfDNA e parâmetros alterados de fertilidade no sêmen, como : baixa viabilidade, alterações na motilidade e morfologia espermática. Análise in vitro complementar confirmou que elevados níveis de S causam estresse oxidativo e diminuem a viabilidade espermática. O conjunto destes resultados corroborou a hipótese de que os níveis de cfDNA poderiam ser marcadores da qualidade espermática geral e estresse oxidativo.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessInfertilidadePolimorfismo Val16Ala SOD2Qualidade espermáticaEstresse oxidativoInfertilityVal16Ala-SOD2 polymorphismSperm qualityOxidative stressCNPQ::CIENCIAS DA SAUDE::FARMACIAEfeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculinaEffect of genetic and pharmacological disbursement of oxidative metabolism in male fertility indicatorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisCruz, Ivana Beatrice Mânica dahttp://lattes.cnpq.br/3426369324110716Fachinetto, Roseleihttp://lattes.cnpq.br/7203076675431306Bresciani, Guilherme Bergamaschihttp://lattes.cnpq.br/1247251997170368Comim, Fabio Vasconcelloshttp://lattes.cnpq.br/5119233991388822Sagrillo, Michele Roratohttp://lattes.cnpq.br/2566285176244747http://lattes.cnpq.br/7742630278309727Costa, Felipe4003000000056000b5fcfe0-b017-4163-80e2-17c110fbcf01e2208229-12a5-4c65-b374-cbc9b69d36e7d4a64262-0e7e-45c5-910e-0b0aee907c1003f335df-7f03-44d1-8866-576fb27afbe0982f3d46-745a-4f4c-83bd-1bbe76793e5be37af8b8-3d08-474c-b996-ee17aaf6b3a8reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
dc.title.alternative.eng.fl_str_mv Effect of genetic and pharmacological disbursement of oxidative metabolism in male fertility indicator
title Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
spellingShingle Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
Costa, Felipe
Infertilidade
Polimorfismo Val16Ala SOD2
Qualidade espermática
Estresse oxidativo
Infertility
Val16Ala-SOD2 polymorphism
Sperm quality
Oxidative stress
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
title_full Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
title_fullStr Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
title_full_unstemmed Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
title_sort Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
author Costa, Felipe
author_facet Costa, Felipe
author_role author
dc.contributor.advisor1.fl_str_mv Cruz, Ivana Beatrice Mânica da
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3426369324110716
dc.contributor.referee1.fl_str_mv Fachinetto, Roselei
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/7203076675431306
dc.contributor.referee2.fl_str_mv Bresciani, Guilherme Bergamaschi
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/1247251997170368
dc.contributor.referee3.fl_str_mv Comim, Fabio Vasconcellos
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/5119233991388822
dc.contributor.referee4.fl_str_mv Sagrillo, Michele Rorato
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/2566285176244747
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/7742630278309727
dc.contributor.author.fl_str_mv Costa, Felipe
contributor_str_mv Cruz, Ivana Beatrice Mânica da
Fachinetto, Roselei
Bresciani, Guilherme Bergamaschi
Comim, Fabio Vasconcellos
Sagrillo, Michele Rorato
dc.subject.por.fl_str_mv Infertilidade
Polimorfismo Val16Ala SOD2
Qualidade espermática
Estresse oxidativo
topic Infertilidade
Polimorfismo Val16Ala SOD2
Qualidade espermática
Estresse oxidativo
Infertility
Val16Ala-SOD2 polymorphism
Sperm quality
Oxidative stress
CNPQ::CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Infertility
Val16Ala-SOD2 polymorphism
Sperm quality
Oxidative stress
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Previous studies indicate that changes in oxidative metabolism may play a role in reproductive success. Manganese-dependent superoxide dismutase enzyme (SOD2), a key in the oxidative balance, presents a genetic variation Val16Ala-SOD2 that leads to a change in its efficiency causing an imbalance between the superoxide (S) and hydrogen peroxide (HP) levels of Cells. Studies have suggested that both homozygous genotypes (AA-VV) cause an S-HP imbalance associated with the risk of various chronic diseases, and interfere with female reproductive success. Thus, the objective of this work was to investigate the effect of the genetic imbalance caused by the polymorphism Val16Ala-SOD2 and pharmacological induced by the treatment with paraquat in oxidative metabolism and in male fertility indicators. For the in vitro analysis of the impact of the S-HP imbalance caused by the pharmacological action of paraquat, a method of quantification of the levels of cfDNA in the seminal plasma was conducted by fluorimetry using the DNA Picogreen. The second protocol investigated the association between the Val16Ala- SOD2 polymorphism with changes in the male fertility parameters determined by the WHO, by evaluating the association of this polymorphism with high levels of cfDNA and markers of oxidative stress in seminal plasma. Semen samples were obtained from healthy volunteers or from surplus samples used to perform sperm in laboratory clinical analyzes, the samples were processed and analyzed in the Biogenomic Laboratory, through spectrophotometric and molecular tests. The results showed a significant association between elevated levels of cfDNA and altered fertility parameters in semen, such as: low viability, changes in motility and sperm morphology. In vitro complementary analysis confirmed that high levels of S causes oxidative stress and decrease sperm viability. These results corroborated the hypothesis that cfDNA levels could be markers of general sperm quality and oxidative stress.
publishDate 2016
dc.date.issued.fl_str_mv 2016-12-07
dc.date.accessioned.fl_str_mv 2019-09-03T19:15:06Z
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dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências da Saúde
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Farmacologia
dc.publisher.initials.fl_str_mv UFSM
dc.publisher.country.fl_str_mv Brasil
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publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências da Saúde
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