Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility?
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.6/1409 |
Resumo: | In the last decades estrogens have been regarded as “male hormones” playing an important role controlling male reproductive function. However, the effect of estrogens regulating testicular function and the spermatogenic process it is not fully addressed. Estrogenic actions in target tissues, including testis, are mediated by hormone interaction with the classical estrogens receptors (ER and ER) and also via the membrane G-protein coupled receptor (GPR30/GPER). Ultimately, the estrogens alter the gene expression network in cells and tissues modulating its functioning. Male fertility relies on a successful spermatogenesis, which is dependent from the support of Sertoli cells (SCs), the somatic cells within seminiferous tubules (SeT). Apoptosis is a key event strictly maintaining the appropriate ratio between germ cells and SCs and, thus, it is crucial to maintain the spermatogenic output. It has been suggested that SCs play a crucial role controlling germ cells fate, by secretion of survival and death factors, which act on receptors in germ cells. These include the survival factor desert hedgehog (Dhh), the stem cell factor (SCF) and its receptor the c-kit, as well as the death factors Fas-Ligand (FasL) and Fas-receptor (FasR). It has been shown that estrogens regulate Dhh, SCF, c-kit, FasL and FasR expression in several other tissues. Therefore, we hypothesize that estrogens may influence germ cell survival or death in testicular cells by governing the expression of SCF, c-kit, FasL, FasR. In the present work rat SeT and SCs were cultured in presence or absence of 100nM of 17β-estradiol (E2), and the expression of the aforementioned factors was studied through real-time PCR and Western blot techniques. In addition, in order to start elucidating the molecular mechanisms by which the estrogenic effects are attained, SCs were cultured with E2 0,1nM and with 100nM of each ER specific agonist: G1, DPN and PPT, respectively, agonists for GPER, ERand ER. E2 down-regulated the c-kit expression while increasing expression of its ligand, SCF, both in SeT and SCs. The expression of Fas system, FasR and FasL was also increased in response to E2. No differences were found in Dhh expression between experimental groups. The expression of SCF and FasL in SCs was strongly increased by G1 stimulation indicating the involvement of GPRER. Our results demonstrated that the estrogenic stimulation may modulate germ cell apoptosis in a direct way or through altering germ cell:SCs communication, which could have a profound impact in male fertility, particularly in cases of hyperestrogenism. |
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Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility?EspermatogéneseApoptoseEstrogéniosTúbulos seminíferosCélulas de SertoliInfertilidade masculinaIn the last decades estrogens have been regarded as “male hormones” playing an important role controlling male reproductive function. However, the effect of estrogens regulating testicular function and the spermatogenic process it is not fully addressed. Estrogenic actions in target tissues, including testis, are mediated by hormone interaction with the classical estrogens receptors (ER and ER) and also via the membrane G-protein coupled receptor (GPR30/GPER). Ultimately, the estrogens alter the gene expression network in cells and tissues modulating its functioning. Male fertility relies on a successful spermatogenesis, which is dependent from the support of Sertoli cells (SCs), the somatic cells within seminiferous tubules (SeT). Apoptosis is a key event strictly maintaining the appropriate ratio between germ cells and SCs and, thus, it is crucial to maintain the spermatogenic output. It has been suggested that SCs play a crucial role controlling germ cells fate, by secretion of survival and death factors, which act on receptors in germ cells. These include the survival factor desert hedgehog (Dhh), the stem cell factor (SCF) and its receptor the c-kit, as well as the death factors Fas-Ligand (FasL) and Fas-receptor (FasR). It has been shown that estrogens regulate Dhh, SCF, c-kit, FasL and FasR expression in several other tissues. Therefore, we hypothesize that estrogens may influence germ cell survival or death in testicular cells by governing the expression of SCF, c-kit, FasL, FasR. In the present work rat SeT and SCs were cultured in presence or absence of 100nM of 17β-estradiol (E2), and the expression of the aforementioned factors was studied through real-time PCR and Western blot techniques. In addition, in order to start elucidating the molecular mechanisms by which the estrogenic effects are attained, SCs were cultured with E2 0,1nM and with 100nM of each ER specific agonist: G1, DPN and PPT, respectively, agonists for GPER, ERand ER. E2 down-regulated the c-kit expression while increasing expression of its ligand, SCF, both in SeT and SCs. The expression of Fas system, FasR and FasL was also increased in response to E2. No differences were found in Dhh expression between experimental groups. The expression of SCF and FasL in SCs was strongly increased by G1 stimulation indicating the involvement of GPRER. Our results demonstrated that the estrogenic stimulation may modulate germ cell apoptosis in a direct way or through altering germ cell:SCs communication, which could have a profound impact in male fertility, particularly in cases of hyperestrogenism.Nas últimas décadas os estrogénios têm sido considerados hormonas masculinas, desempenhando um papel importante no controlo das funções reprodutivas masculinas. Contudo, o efeito dos estrogénios na regulação das funções testiculares ainda não está completamente abordado. As ações estrogénicas nos tecidos alvo, entre eles o testículo, são mediadas por interações hormonais com os recetores de estrogénios (ER e ER) clássicos e também através do recetor membranar associado à proteína-G (GPR30/GPER). Por fim, os estrogénios alteram a rede de expressão dos genes nas células e nos tecidos, modulando o seu funcionamento. A fertilidade masculina assenta numa espermatogénese bem sucedida, a qual é dependente do suporte das células de Sertoli (SCs), as células somáticas presentes nos túbulos seminíferos (SeT). A apoptose é o evento chave que mantem o ratio apropriado entre as células germinativas e as SCs e desta forma é crucial para manter a qualidade e quantidade do processo espermatogénico. Tem sido sugerido que as SCs desempenham um papel crucial no controlo do destino das células germinativas através da secreção de fatores de sobrevivência/morte, que atuam nos recetores nas células germinativas. Esses incluem o fator de sobrevivência Desert Hedgehog (Dhh), o Stem Cell Factor (SCF) e o seu receptor (c-kit), assim como os fatores de morte Fas Ligando (FasL) e o seu recetor (FasR). Tem sido demonstrado que os estrogénios regulam a expressão do Dhh, SCF, c-kit, FasL e FasR em diversos tecidos. Portanto colocou-se a hipótese de que os estrogénios podem influenciar a sobrevivência ou morte das células testiculares através do controlo da expressão dos referidos genes. Neste trabalho, SeT e SCs de rato foram colocados em cultura na presença ou ausência de 100nM de 17β-estradiol (E2), e a expressão dos fatores acima-citados foi estuda através das técnicas de Real-Time PCR e Western Blot. Além disso, para elucidar qual o mecanismo molecular pelo qual o efeito dos estrogénios é conseguido, SCs foram colocadas em cultura na presença de 100 nM E2 ou 100nM de agonistas específicos para cada um dos recetores: G1, DPN e PPT, respetivamente, agonistas para o GPER, ERα e ERβ. O E2 diminuiu a expressão do c-kit enquanto por sua vez expressão do seu ligando SCF aumentou. Não houve diferenças na expressão do Dhh entre os diferentes grupos experimentais. A expressão do SCF e do FasL nas SCs foi muito aumentada pela estimulação com G1 indicando o envolvimento do GPER. Os nossos resultados demonstram que a estimulação com estrogénios pode moldar a apoptose das células germinativas tanto de uma forma directa como através da alteração da comunicação entre as SCs e as células germinativas, podendo isto ter um profundo impacto na fertilidade masculina em especial nos casos de hiperesteroidismo.Universidade da Beira InteriorSocorro, Sílvia Cristina da Cruz MarquesOliveira, Pedro FontesuBibliorumAlves, Mário Rui Castanheira2013-10-09T13:41:51Z2013-062013-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.6/1409enginfo: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:RCAAP2023-12-15T09:36:57Zoai:ubibliorum.ubi.pt:10400.6/1409Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:43:13.917966Repositório 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 |
Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility? |
title |
Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility? |
spellingShingle |
Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility? Alves, Mário Rui Castanheira Espermatogénese Apoptose Estrogénios Túbulos seminíferos Células de Sertoli Infertilidade masculina |
title_short |
Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility? |
title_full |
Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility? |
title_fullStr |
Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility? |
title_full_unstemmed |
Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility? |
title_sort |
Estrogens regulate the survival and death communication between Sertoli and germ cells: a clue for male infertility? |
author |
Alves, Mário Rui Castanheira |
author_facet |
Alves, Mário Rui Castanheira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Socorro, Sílvia Cristina da Cruz Marques Oliveira, Pedro Fontes uBibliorum |
dc.contributor.author.fl_str_mv |
Alves, Mário Rui Castanheira |
dc.subject.por.fl_str_mv |
Espermatogénese Apoptose Estrogénios Túbulos seminíferos Células de Sertoli Infertilidade masculina |
topic |
Espermatogénese Apoptose Estrogénios Túbulos seminíferos Células de Sertoli Infertilidade masculina |
description |
In the last decades estrogens have been regarded as “male hormones” playing an important role controlling male reproductive function. However, the effect of estrogens regulating testicular function and the spermatogenic process it is not fully addressed. Estrogenic actions in target tissues, including testis, are mediated by hormone interaction with the classical estrogens receptors (ER and ER) and also via the membrane G-protein coupled receptor (GPR30/GPER). Ultimately, the estrogens alter the gene expression network in cells and tissues modulating its functioning. Male fertility relies on a successful spermatogenesis, which is dependent from the support of Sertoli cells (SCs), the somatic cells within seminiferous tubules (SeT). Apoptosis is a key event strictly maintaining the appropriate ratio between germ cells and SCs and, thus, it is crucial to maintain the spermatogenic output. It has been suggested that SCs play a crucial role controlling germ cells fate, by secretion of survival and death factors, which act on receptors in germ cells. These include the survival factor desert hedgehog (Dhh), the stem cell factor (SCF) and its receptor the c-kit, as well as the death factors Fas-Ligand (FasL) and Fas-receptor (FasR). It has been shown that estrogens regulate Dhh, SCF, c-kit, FasL and FasR expression in several other tissues. Therefore, we hypothesize that estrogens may influence germ cell survival or death in testicular cells by governing the expression of SCF, c-kit, FasL, FasR. In the present work rat SeT and SCs were cultured in presence or absence of 100nM of 17β-estradiol (E2), and the expression of the aforementioned factors was studied through real-time PCR and Western blot techniques. In addition, in order to start elucidating the molecular mechanisms by which the estrogenic effects are attained, SCs were cultured with E2 0,1nM and with 100nM of each ER specific agonist: G1, DPN and PPT, respectively, agonists for GPER, ERand ER. E2 down-regulated the c-kit expression while increasing expression of its ligand, SCF, both in SeT and SCs. The expression of Fas system, FasR and FasL was also increased in response to E2. No differences were found in Dhh expression between experimental groups. The expression of SCF and FasL in SCs was strongly increased by G1 stimulation indicating the involvement of GPRER. Our results demonstrated that the estrogenic stimulation may modulate germ cell apoptosis in a direct way or through altering germ cell:SCs communication, which could have a profound impact in male fertility, particularly in cases of hyperestrogenism. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-10-09T13:41:51Z 2013-06 2013-06-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.6/1409 |
url |
http://hdl.handle.net/10400.6/1409 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade da Beira Interior |
publisher.none.fl_str_mv |
Universidade da Beira Interior |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799136332388237312 |