The epididymis as a target of endocrine disruption: a metabolic perspective
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.6/12538 |
Resumo: | Male fertility depends on the output of spermatogenic processe, as well as on the maturation events occurring during sperm passage throughout the epididymis. Epididymis plays an important role in storage of sperm, and also increasing their concentration and providing immunological and oxidative stress protection. In order to perform its functions, the epididymis depends on glucose metabolism as energy source, and also contributes by its secretory activity to establish the composition of the epididymal fluid. Recently, it was demonstrated that several energy pathways are active in this organ, namely glycolysis, and several metabolites like pyruvate are detected in the epididymal fluid. Also, the epididymal milieu has been shown to be rich in lipids, a class of macromolecules that plays a crucial role in the structure of sperm membrane influencing fertilization capacity. The activity of the epididymis can be regulated by hormones, like androgens, that can also have an influence on its metabolism. Endocrine disruptors (EDCs) are exogenous compounds capable of perturbing the normal hormone signalling. The EDC vinclozolin (VNZ) acts as anti-androgen and has been shown to affect male reproduction. However, the effect of VNZ in the epididymis, namely in the deregulation of metabolism is largely unknown. The present dissertation investigates the impact of VNZ exposure in the rat epididymis glycolytic and lipidic metabolism. For this purpose, caput epididymis sections were cultured ex vivo in the presence or absence of VNZ 500 µM. Glucose consumption, lactate production, and the expression and activity of glycolytic and lipid metabolism regulators were evaluated by spectrophotometric assays and Western blot analysis. The results obtained showed that VNZ increased glucose consumption in the caput epididymis, whereas decreasing lactate production. Also, VNZ activated both fatty acid biosynthesis and degradation. These findings first demonstrated that VNZ disrupts glycolytic and lipid metabolism in the epididymis and highlight for the impact that this and others EDCs may have affecting sperm quality and male fertility. |
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The epididymis as a target of endocrine disruption: a metabolic perspective(in)Fertilidade MasculinaDesreguladores EndócrinosEpidídimoMetabolismoVinclozolinaDomínio/Área Científica::Engenharia e Tecnologia::BioquímicaMale fertility depends on the output of spermatogenic processe, as well as on the maturation events occurring during sperm passage throughout the epididymis. Epididymis plays an important role in storage of sperm, and also increasing their concentration and providing immunological and oxidative stress protection. In order to perform its functions, the epididymis depends on glucose metabolism as energy source, and also contributes by its secretory activity to establish the composition of the epididymal fluid. Recently, it was demonstrated that several energy pathways are active in this organ, namely glycolysis, and several metabolites like pyruvate are detected in the epididymal fluid. Also, the epididymal milieu has been shown to be rich in lipids, a class of macromolecules that plays a crucial role in the structure of sperm membrane influencing fertilization capacity. The activity of the epididymis can be regulated by hormones, like androgens, that can also have an influence on its metabolism. Endocrine disruptors (EDCs) are exogenous compounds capable of perturbing the normal hormone signalling. The EDC vinclozolin (VNZ) acts as anti-androgen and has been shown to affect male reproduction. However, the effect of VNZ in the epididymis, namely in the deregulation of metabolism is largely unknown. The present dissertation investigates the impact of VNZ exposure in the rat epididymis glycolytic and lipidic metabolism. For this purpose, caput epididymis sections were cultured ex vivo in the presence or absence of VNZ 500 µM. Glucose consumption, lactate production, and the expression and activity of glycolytic and lipid metabolism regulators were evaluated by spectrophotometric assays and Western blot analysis. The results obtained showed that VNZ increased glucose consumption in the caput epididymis, whereas decreasing lactate production. Also, VNZ activated both fatty acid biosynthesis and degradation. These findings first demonstrated that VNZ disrupts glycolytic and lipid metabolism in the epididymis and highlight for the impact that this and others EDCs may have affecting sperm quality and male fertility.A fertilidade masculina depende da eficiência do processo espermatogénico, assim como do conjunto de eventos que ocorrem durante a passagem dos espermatozoides pelo epidídimo e que são responsáveis pela sua maturação. Este órgão tem também um papel importante no armazenamento dos espermatozoides, aumentando a sua concentração, e conferindo-lhes proteção imunológica e contra o stress oxidativo. Para desempenhar as suas funções, o epidídimo depende do metabolismo da glicose como fonte de energia, e resultado da sua atividade secretora contribui para estabelecer a composição do fluido epididimal. Recentemente, foi demonstrado que existem várias vias energéticas ativas no epidídimo, como a glicólise, e vários metabolitos como o piruvato foram detetados no fluído epididimal. Além disso, o meio epididimal demonstrou ser rico em lípidos, uma classe de macromoléculas que desempenha um papel crucial na estrutura da membrana espermática influenciando a capacidade de fertilização. A atividade do epidídimo é regulada pela ação de hormonas, como os androgénios, os quais podem também influenciar o metabolismo deste órgão. Os disruptores endócrinos (EDCs) são compostos exógenos capazes de perturbar a normal sinalização hormonal. A vinclozolina (VNZ) é um EDC que atua como anti-androgénio e cuja ação demonstrou afetar a reprodução masculina. No entanto, o efeito da VNZ no epidídimo, nomeadamente na desregulação do metabolismo, é largamente desconhecido. A presente dissertação investiga o impacto da exposição à VNZ no metabolismo glicolítico e lipídico do epidídimo de ratos. Para este fim, seções da região caput do epidídimo foram mantidas em cultura ex vivo na presença ou ausência de VNZ 500 µM. O consumo de glicose, a produção de lactato e a expressão e atividade de reguladores do metabolismo glicolítico e lipídico foram avaliados por ensaios espetrofotométricos e análise de Western blot. Os resultados obtidos mostraram que a VNZ aumentou o consumo de glicose pelas células da região caput do epidídimo, enquanto diminuiu a produção de lactato. Além disso, a VNZ ativou a biossíntese e a degradação de ácidos gordos. Estes achados demonstraram pela primeira vez que a VNZ desregula o metabolismo glicolítico e lipídico no epidídimo e alertam para o impacto que este e outros EDCs podem ter na qualidade dos espermatozoides e fertilidade masculina.Correia, Sara Carina de LimaSocorro, Sílvia Cristina da Cruz MarquesSousa, Ana Catarina AlmeidauBibliorumTavares, Daniel Alexandre Ferreira2022-12-19T10:16:42Z2022-07-272022-06-302022-07-27T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/12538TID:203115350enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-15T09:55:45Zoai:ubibliorum.ubi.pt:10400.6/12538Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:52:07.378137Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The epididymis as a target of endocrine disruption: a metabolic perspective |
title |
The epididymis as a target of endocrine disruption: a metabolic perspective |
spellingShingle |
The epididymis as a target of endocrine disruption: a metabolic perspective Tavares, Daniel Alexandre Ferreira (in)Fertilidade Masculina Desreguladores Endócrinos Epidídimo Metabolismo Vinclozolina Domínio/Área Científica::Engenharia e Tecnologia::Bioquímica |
title_short |
The epididymis as a target of endocrine disruption: a metabolic perspective |
title_full |
The epididymis as a target of endocrine disruption: a metabolic perspective |
title_fullStr |
The epididymis as a target of endocrine disruption: a metabolic perspective |
title_full_unstemmed |
The epididymis as a target of endocrine disruption: a metabolic perspective |
title_sort |
The epididymis as a target of endocrine disruption: a metabolic perspective |
author |
Tavares, Daniel Alexandre Ferreira |
author_facet |
Tavares, Daniel Alexandre Ferreira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Correia, Sara Carina de Lima Socorro, Sílvia Cristina da Cruz Marques Sousa, Ana Catarina Almeida uBibliorum |
dc.contributor.author.fl_str_mv |
Tavares, Daniel Alexandre Ferreira |
dc.subject.por.fl_str_mv |
(in)Fertilidade Masculina Desreguladores Endócrinos Epidídimo Metabolismo Vinclozolina Domínio/Área Científica::Engenharia e Tecnologia::Bioquímica |
topic |
(in)Fertilidade Masculina Desreguladores Endócrinos Epidídimo Metabolismo Vinclozolina Domínio/Área Científica::Engenharia e Tecnologia::Bioquímica |
description |
Male fertility depends on the output of spermatogenic processe, as well as on the maturation events occurring during sperm passage throughout the epididymis. Epididymis plays an important role in storage of sperm, and also increasing their concentration and providing immunological and oxidative stress protection. In order to perform its functions, the epididymis depends on glucose metabolism as energy source, and also contributes by its secretory activity to establish the composition of the epididymal fluid. Recently, it was demonstrated that several energy pathways are active in this organ, namely glycolysis, and several metabolites like pyruvate are detected in the epididymal fluid. Also, the epididymal milieu has been shown to be rich in lipids, a class of macromolecules that plays a crucial role in the structure of sperm membrane influencing fertilization capacity. The activity of the epididymis can be regulated by hormones, like androgens, that can also have an influence on its metabolism. Endocrine disruptors (EDCs) are exogenous compounds capable of perturbing the normal hormone signalling. The EDC vinclozolin (VNZ) acts as anti-androgen and has been shown to affect male reproduction. However, the effect of VNZ in the epididymis, namely in the deregulation of metabolism is largely unknown. The present dissertation investigates the impact of VNZ exposure in the rat epididymis glycolytic and lipidic metabolism. For this purpose, caput epididymis sections were cultured ex vivo in the presence or absence of VNZ 500 µM. Glucose consumption, lactate production, and the expression and activity of glycolytic and lipid metabolism regulators were evaluated by spectrophotometric assays and Western blot analysis. The results obtained showed that VNZ increased glucose consumption in the caput epididymis, whereas decreasing lactate production. Also, VNZ activated both fatty acid biosynthesis and degradation. These findings first demonstrated that VNZ disrupts glycolytic and lipid metabolism in the epididymis and highlight for the impact that this and others EDCs may have affecting sperm quality and male fertility. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-19T10:16:42Z 2022-07-27 2022-06-30 2022-07-27T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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eng |
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