AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO

Detalhes bibliográficos
Ano de defesa: 2021
Autor(a) principal: Sleiman, Hanan Khaled lattes
Orientador(a): Romano, Marco Aurélio lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Estadual do Centro-Oeste
Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Farmacêuticas (Doutorado)
Departamento: Unicentro::Departamento de Farmácia
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://tede.unicentro.br:8080/jspui/handle/jspui/1760
Resumo: The hypothalamic-pituitary-testicular (HHT) axis encompasses the male reproductive system, which during fetal life is developed and in postnatal life undergoes sexual differentiation in the brain. Phytoestrogens are substances that occur naturally in vegetables and have biological functions in relation to them. Soy is a food widely consumed by the population and in its composition is isoflavone, a flavonoid, which has the following main bioforms: genistein, daizein, glycitein and equol, found in the form of aglycone or glycosides. Despite the beneficial effects of isoflavones, such as herbal medicines used to improve postmenopausal symptoms, antioxidants, acting in the prevention of diseases related to the heart and osteoporosis, studies show that it can act as an endocrine disruptor. The endocrine disrupting effect damages human health, acting on any part of the endocrine system by blocking or mimicking the action of naturally produced hormones. Isoflavones, as they present a chemical structure similar to 17β-estradiol, a naturally produced estrogen, compete for the same binding site as estrogen receptors. The objective of this study was to evaluate whether exposure to isoflavones, during the sexual differentiation window (critical phase of development), causes changes in the HHT axis. Newly weaned prepubertal Wistar rats were treated with three different concentrations of isoflavone: 0.5 mg /Kg; 5 mg /Kg; 50 mg /Kg. In addition to these three treatment groups, a control group treated with corn oil diluent was also used. All animals received their corresponding doses daily through gavage (forced ingestion by tube) in the morning, after weighing. Treatment started at PND 23 and ended at PND 60. The evolution of age and weight at puberty was assessed daily. At the end of the experiment, the animals were euthanized under general anesthesia, cardiac puncture and beheading. The tissues were collected for further analysis. The blood was collected for hormonal analyzes of testosterone, estradiol, LH and FSH. The testicles, epididymides and seminal vesicle were removed for weighing, evaluation of sperm production and integrity, evaluation of the integrity of the acrosome, evaluation of mitochondrial activity and sperm morphology. One of the testicles was used to identify alterations in gene expression, which participate in the regulation of spermatogenesis, through real-time quantitative PCR (RT-qPCR). The data obtained were performed using the software Statistica 7.0, Statsoft Inc. Statistical differences were considered when p <0.05. Exposure to isoflavones in the prepubertal age did not change the weight at puberty of the animals, nor did it change the weight of dependent androgen tissues, but there was a delay in age at puberty in the treated groups 0.05 mg / kg and 5 mg / kg. It was observed that the total sperm production / testis was reduced in the treated group by 0.5 mg / kg, since when the total sperm production / gram testis is evaluated, there are no significant differences. When the daily sperm production / testicle was evaluated, the animals treated 0.5 mg / kg and 50 mg / kg showed a reduction in this parameter, whereas when the daily sperm production / gram testicle was evaluated, there were no significant differences. Regarding the sperm reserve in the epididymis, in the three treated groups there was less sperm concentration. The sperm transit time in the epididymis was affected in the tail portion of the treated animals 5 mg / kg, where a faster passage of the seminal fluid occurs. The integrity of the acrosome and the integrity of the plasma membrane of the sperm was affected in all treated groups, indicating lower sperm fertilization capacity, reduced fertility and shorter survival. Mitochondrial activity, related to motility, was reduced in the treated groups 0.5 mg / kg and 50 mg / kg, as well as their structure and functionality, assessed by sperm pathology. In gene expression, there were no results with significant differences. In the hormonal profile of testosterone and estradiol, both presented a reduction in the treated groups of 0.5 mg / kg and 5 mg / kg. FSH was increased in the treated group 0.5 mg / kg and LH in the treated groups 5 mg / kg and 50 mg / kg. These results demonstrate that the exposure to isoflavones during the critical period of sexual differentiation, modifies the activity of the hypothalamic-pituitary-testicular axis, which has negative consequences on the reproduction of animals when they are adults.
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spelling Romano, Marco Auréliohttp://lattes.cnpq.br/1024434825015654066.684.559-05http://lattes.cnpq.br/8058204156380693Sleiman, Hanan Khaled2021-11-22T16:22:54Z2021-04-16Sleiman, Hanan Khaled. AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO. 2021. 65 f. Tese (Programa de Pós-Graduação em Ciências Farmacêuticas - Doutorado) - Universidade Estadual do Centro-Oeste, Guarapuava-PR.http://tede.unicentro.br:8080/jspui/handle/jspui/1760The hypothalamic-pituitary-testicular (HHT) axis encompasses the male reproductive system, which during fetal life is developed and in postnatal life undergoes sexual differentiation in the brain. Phytoestrogens are substances that occur naturally in vegetables and have biological functions in relation to them. Soy is a food widely consumed by the population and in its composition is isoflavone, a flavonoid, which has the following main bioforms: genistein, daizein, glycitein and equol, found in the form of aglycone or glycosides. Despite the beneficial effects of isoflavones, such as herbal medicines used to improve postmenopausal symptoms, antioxidants, acting in the prevention of diseases related to the heart and osteoporosis, studies show that it can act as an endocrine disruptor. The endocrine disrupting effect damages human health, acting on any part of the endocrine system by blocking or mimicking the action of naturally produced hormones. Isoflavones, as they present a chemical structure similar to 17β-estradiol, a naturally produced estrogen, compete for the same binding site as estrogen receptors. The objective of this study was to evaluate whether exposure to isoflavones, during the sexual differentiation window (critical phase of development), causes changes in the HHT axis. Newly weaned prepubertal Wistar rats were treated with three different concentrations of isoflavone: 0.5 mg /Kg; 5 mg /Kg; 50 mg /Kg. In addition to these three treatment groups, a control group treated with corn oil diluent was also used. All animals received their corresponding doses daily through gavage (forced ingestion by tube) in the morning, after weighing. Treatment started at PND 23 and ended at PND 60. The evolution of age and weight at puberty was assessed daily. At the end of the experiment, the animals were euthanized under general anesthesia, cardiac puncture and beheading. The tissues were collected for further analysis. The blood was collected for hormonal analyzes of testosterone, estradiol, LH and FSH. The testicles, epididymides and seminal vesicle were removed for weighing, evaluation of sperm production and integrity, evaluation of the integrity of the acrosome, evaluation of mitochondrial activity and sperm morphology. One of the testicles was used to identify alterations in gene expression, which participate in the regulation of spermatogenesis, through real-time quantitative PCR (RT-qPCR). The data obtained were performed using the software Statistica 7.0, Statsoft Inc. Statistical differences were considered when p <0.05. Exposure to isoflavones in the prepubertal age did not change the weight at puberty of the animals, nor did it change the weight of dependent androgen tissues, but there was a delay in age at puberty in the treated groups 0.05 mg / kg and 5 mg / kg. It was observed that the total sperm production / testis was reduced in the treated group by 0.5 mg / kg, since when the total sperm production / gram testis is evaluated, there are no significant differences. When the daily sperm production / testicle was evaluated, the animals treated 0.5 mg / kg and 50 mg / kg showed a reduction in this parameter, whereas when the daily sperm production / gram testicle was evaluated, there were no significant differences. Regarding the sperm reserve in the epididymis, in the three treated groups there was less sperm concentration. The sperm transit time in the epididymis was affected in the tail portion of the treated animals 5 mg / kg, where a faster passage of the seminal fluid occurs. The integrity of the acrosome and the integrity of the plasma membrane of the sperm was affected in all treated groups, indicating lower sperm fertilization capacity, reduced fertility and shorter survival. Mitochondrial activity, related to motility, was reduced in the treated groups 0.5 mg / kg and 50 mg / kg, as well as their structure and functionality, assessed by sperm pathology. In gene expression, there were no results with significant differences. In the hormonal profile of testosterone and estradiol, both presented a reduction in the treated groups of 0.5 mg / kg and 5 mg / kg. FSH was increased in the treated group 0.5 mg / kg and LH in the treated groups 5 mg / kg and 50 mg / kg. These results demonstrate that the exposure to isoflavones during the critical period of sexual differentiation, modifies the activity of the hypothalamic-pituitary-testicular axis, which has negative consequences on the reproduction of animals when they are adults.O eixo hipotalâmico-hipofisário-testicular (HHT) engloba o sistema reprodutor masculino, que durante a vida fetal é desenvolvido e na vida pós-natal sofre diferenciação sexual no cérebro. Os fitoestrógenos são substâncias que ocorrem naturalmente em vegetais e nos mesmos apresentam funções biológicas.. A soja é um alimento largamente consumido pela população e em sua composição está a isoflavona, um flavonóide, que apresenta as seguintes bioformas principais: genisteína, daizeína, gliciteína e equol, encontradas na forma de agliconas ou glicosídeos. Apesar dos efeitos benéficos das isoflavonas, como fitoterápicos utilizados na melhora de sintomas pósmenopausa, antioxidantes, agindo na prevenção de doenças relacionadas ao coração e a osteoporose, estudos demonstram que a mesma pode atuar como um desregulador endócrino. O efeito de desregulação endócrino causa danos a saúde humana, agindo sobre qualquer parte do sistema endócrino bloqueando ou mimetizando a ação de hormônios naturalmente produzidos. As isoflavonas, por apresentarem estrutura química semelhante ao 17β-estradiol, estrógeno naturalmente produzido, competem pelo mesmo sítio de ligação dos receptores estrogênicos. O objetivo deste trabalho foi avaliar se a exposição às isoflavonas, durante a janela de diferenciação sexual (fase crítica do desenvolvimento), causa alteração no eixo HHT. Ratos Wistar pré-púberes, recém-desmamados, foram tratados com três diferentes concentrações de isoflavona: 0,5 mg /Kg; 5 mg /Kg; 50 mg /Kg. Além desses três grupos de tratamento, ainda foi utilizado um grupo controle tratado com o diluente óleo de milho. Todos os animais receberam suas correspondentes doses diariamente através de gavagem (ingestão forçada por sonda) pela manhã, após pesagem. O tratamento iniciou-se no PND (dia pós nascimento) 23 e foi finalizado no PND 60. A evolução de idade e peso a puberdade foi avaliada diariamente. Ao final do experimento os animais foram eutanasiados sob anestesia geral, punção cardíaca e decapitação. Os tecidos foram colhidos para análise posterior. O sangue foi coletado para análises hormonais de testosterona, estradiol, LH e FSH. Os testículos, epidídimos e vesícula seminal foram retirados para pesagem, avaliação da produção e integridade espermática, avaliação da integridade do acrossomo, avaliação da atividade mitocondrial e da morfologia espermática. Um dos testículos foi utilizado para identificação das alterações de expressão gênica, que participam da regulação da espermatogênese, através de PCR quantitativo em tempo real (RT-qPCR). Os dados obtidos foram efetuados com a utilização do software Statistica 7.0, Statsoft Inc. Consideraram-se diferenças estatísticas quando p<0,05. A exposição as isoflavonas na idade pré-púbere, não alterou o peso a puberdade dos animais, assim como não alterou o peso dos tecidos andrógenos dependentes, porém houve atraso na idade a puberdade dos grupos tratados 0,5 mg/kg e 5 mg/kg. Observouse que a produção espermática total/testículo foi reduzida no grupo tratado 0,5 mg/kg, já quando avaliada a produção espermática total/por grama testículo, não houve diferenças significativas. Quando avaliada a produção espermática diária/testículo, os animais tratados 0,5 mg/kg e 50 mg/kg apresentaram redução nesse parâmetro, já quando avaliada a produção espermática diária/por grama testículo, não há diferenças significativas. Em relação a reserva espermática no epidídimo, nos três grupos tratados verificou-se menor concentração espermática. O tempo de trânsito espermático nos epidídimos foi afetado na porção cauda dos animais tratados 5 mg/kg, onde ocorre uma passagem mais rápida do fluido seminal. A integridade do acrossomo e a integridade da membrana plasmática do espermatozoide foi afetada em todos os grupos tratados, indicativo de menor capacidade fecundante do espermatozoide, fertilidade reduzida e menor sobrevida destes. A atividade mitocondrial, relacionada a motilidade foi reduzida nos grupos tratados 0,5 mg/kg e 50 mg/kg, assim como a estrutura e funcionalidade destes, avaliada pela patologia espermática. Na expressão gênica não observou-se resultados com diferenças significativas. No perfil hormonal de testosterona e estradiol, ambos apresentaram-se com redução nos grupos tratados com 0,5 mg/kg e 5 mg/kg. O FSH apresentou-se aumentado no grupo tratado 0,5 mg/kg e LH nos grupos tratados 5 mg/kg e 50 mg/kg. Estes resultados demonstram, que a exposição as isoflavonas durante o período crítico de diferenciação sexual, modifica a atividade do eixo hipotalâmico-hipofisário-testicular, o que traz consequências negativas na reprodução dos animais quando na idade adulta.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2021-11-22T16:22:54Z No. of bitstreams: 1 TESE Hanan Khaled Sleiman.pdf: 1206652 bytes, checksum: 450fa17f0bd191dd587921cfa675a519 (MD5)Made available in DSpace on 2021-11-22T16:22:54Z (GMT). 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dc.title.por.fl_str_mv AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO
title AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO
spellingShingle AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO
Sleiman, Hanan Khaled
Fitoestrógeno
Isoflavonas
Desregulador endócrino
Phytoestrogen
Isoflavones
Endocrine disruptor
CIENCIAS DA SAUDE::FARMACIA
title_short AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO
title_full AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO
title_fullStr AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO
title_full_unstemmed AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO
title_sort AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO
author Sleiman, Hanan Khaled
author_facet Sleiman, Hanan Khaled
author_role author
dc.contributor.advisor1.fl_str_mv Romano, Marco Aurélio
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1024434825015654
dc.contributor.authorID.fl_str_mv 066.684.559-05
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8058204156380693
dc.contributor.author.fl_str_mv Sleiman, Hanan Khaled
contributor_str_mv Romano, Marco Aurélio
dc.subject.por.fl_str_mv Fitoestrógeno
Isoflavonas
Desregulador endócrino
topic Fitoestrógeno
Isoflavonas
Desregulador endócrino
Phytoestrogen
Isoflavones
Endocrine disruptor
CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Phytoestrogen
Isoflavones
Endocrine disruptor
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::FARMACIA
description The hypothalamic-pituitary-testicular (HHT) axis encompasses the male reproductive system, which during fetal life is developed and in postnatal life undergoes sexual differentiation in the brain. Phytoestrogens are substances that occur naturally in vegetables and have biological functions in relation to them. Soy is a food widely consumed by the population and in its composition is isoflavone, a flavonoid, which has the following main bioforms: genistein, daizein, glycitein and equol, found in the form of aglycone or glycosides. Despite the beneficial effects of isoflavones, such as herbal medicines used to improve postmenopausal symptoms, antioxidants, acting in the prevention of diseases related to the heart and osteoporosis, studies show that it can act as an endocrine disruptor. The endocrine disrupting effect damages human health, acting on any part of the endocrine system by blocking or mimicking the action of naturally produced hormones. Isoflavones, as they present a chemical structure similar to 17β-estradiol, a naturally produced estrogen, compete for the same binding site as estrogen receptors. The objective of this study was to evaluate whether exposure to isoflavones, during the sexual differentiation window (critical phase of development), causes changes in the HHT axis. Newly weaned prepubertal Wistar rats were treated with three different concentrations of isoflavone: 0.5 mg /Kg; 5 mg /Kg; 50 mg /Kg. In addition to these three treatment groups, a control group treated with corn oil diluent was also used. All animals received their corresponding doses daily through gavage (forced ingestion by tube) in the morning, after weighing. Treatment started at PND 23 and ended at PND 60. The evolution of age and weight at puberty was assessed daily. At the end of the experiment, the animals were euthanized under general anesthesia, cardiac puncture and beheading. The tissues were collected for further analysis. The blood was collected for hormonal analyzes of testosterone, estradiol, LH and FSH. The testicles, epididymides and seminal vesicle were removed for weighing, evaluation of sperm production and integrity, evaluation of the integrity of the acrosome, evaluation of mitochondrial activity and sperm morphology. One of the testicles was used to identify alterations in gene expression, which participate in the regulation of spermatogenesis, through real-time quantitative PCR (RT-qPCR). The data obtained were performed using the software Statistica 7.0, Statsoft Inc. Statistical differences were considered when p <0.05. Exposure to isoflavones in the prepubertal age did not change the weight at puberty of the animals, nor did it change the weight of dependent androgen tissues, but there was a delay in age at puberty in the treated groups 0.05 mg / kg and 5 mg / kg. It was observed that the total sperm production / testis was reduced in the treated group by 0.5 mg / kg, since when the total sperm production / gram testis is evaluated, there are no significant differences. When the daily sperm production / testicle was evaluated, the animals treated 0.5 mg / kg and 50 mg / kg showed a reduction in this parameter, whereas when the daily sperm production / gram testicle was evaluated, there were no significant differences. Regarding the sperm reserve in the epididymis, in the three treated groups there was less sperm concentration. The sperm transit time in the epididymis was affected in the tail portion of the treated animals 5 mg / kg, where a faster passage of the seminal fluid occurs. The integrity of the acrosome and the integrity of the plasma membrane of the sperm was affected in all treated groups, indicating lower sperm fertilization capacity, reduced fertility and shorter survival. Mitochondrial activity, related to motility, was reduced in the treated groups 0.5 mg / kg and 50 mg / kg, as well as their structure and functionality, assessed by sperm pathology. In gene expression, there were no results with significant differences. In the hormonal profile of testosterone and estradiol, both presented a reduction in the treated groups of 0.5 mg / kg and 5 mg / kg. FSH was increased in the treated group 0.5 mg / kg and LH in the treated groups 5 mg / kg and 50 mg / kg. These results demonstrate that the exposure to isoflavones during the critical period of sexual differentiation, modifies the activity of the hypothalamic-pituitary-testicular axis, which has negative consequences on the reproduction of animals when they are adults.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-11-22T16:22:54Z
dc.date.issued.fl_str_mv 2021-04-16
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dc.identifier.citation.fl_str_mv Sleiman, Hanan Khaled. AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO. 2021. 65 f. Tese (Programa de Pós-Graduação em Ciências Farmacêuticas - Doutorado) - Universidade Estadual do Centro-Oeste, Guarapuava-PR.
dc.identifier.uri.fl_str_mv http://tede.unicentro.br:8080/jspui/handle/jspui/1760
identifier_str_mv Sleiman, Hanan Khaled. AÇÃO HORMONAL DE ISOFLAVONAS NA PRÉ-PUBERDADE EM RATOS WISTAR COMO MODELO EXPERIMENTAL ENDÓCRINO. 2021. 65 f. Tese (Programa de Pós-Graduação em Ciências Farmacêuticas - Doutorado) - Universidade Estadual do Centro-Oeste, Guarapuava-PR.
url http://tede.unicentro.br:8080/jspui/handle/jspui/1760
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dc.publisher.none.fl_str_mv Universidade Estadual do Centro-Oeste
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dc.publisher.department.fl_str_mv Unicentro::Departamento de Farmácia
publisher.none.fl_str_mv Universidade Estadual do Centro-Oeste
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