Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | 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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Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculinaEffect of genetic and pharmacological disbursement of oxidative metabolism in male fertility indicatorInfertilidadePolimorfismo Val16Ala SOD2Qualidade espermáticaEstresse oxidativoInfertilityVal16Ala-SOD2 polymorphismSperm qualityOxidative stressCNPQ::CIENCIAS DA SAUDE::FARMACIAPrevious 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.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdeCruz, 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/2566285176244747Costa, Felipe2019-09-03T19:15:06Z2019-09-03T19:15:06Z2016-12-07info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/18127porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2019-09-04T06:02:37Zoai:repositorio.ufsm.br:1/18127Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-09-04T06:02:37Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeito do desbalanço genético e farmacológico do metabolismo oxidativo em indicadores de fertilidade masculina 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.none.fl_str_mv |
Cruz, Ivana Beatrice Mânica da http://lattes.cnpq.br/3426369324110716 Fachinetto, Roselei http://lattes.cnpq.br/7203076675431306 Bresciani, Guilherme Bergamaschi http://lattes.cnpq.br/1247251997170368 Comim, Fabio Vasconcellos http://lattes.cnpq.br/5119233991388822 Sagrillo, Michele Rorato http://lattes.cnpq.br/2566285176244747 |
dc.contributor.author.fl_str_mv |
Costa, Felipe |
dc.subject.por.fl_str_mv |
Infertilidade Polimorfismo Val16Ala SOD2 Qualidade espermática Estresse oxidativo Infertility Val16Ala-SOD2 polymorphism Sperm quality Oxidative stress CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Infertilidade Polimorfismo Val16Ala SOD2 Qualidade espermática Estresse oxidativo Infertility Val16Ala-SOD2 polymorphism Sperm quality Oxidative stress 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.none.fl_str_mv |
2016-12-07 2019-09-03T19:15:06Z 2019-09-03T19:15:06Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/18127 |
url |
http://repositorio.ufsm.br/handle/1/18127 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805922130957697024 |