Is Genistein a Threat to Male Reproductive Potential?

Bibliographic Details
Main Author: Yashechkina, Tatiana
Publication Date: 2017
Format: Master thesis
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10773/21954
Summary: Genistein is one of the most abundant phytoestrogens in soybeans. Because of its chemical similarity to endogenous estrogens, genistein can bind to estrogen receptors (ERs) present in cells and mediate an estrogenic response. Its estrogenic action may potentially interfere with normal functioning of various systems in the human organism, including the reproductive system which is highly regulated by sex hormones. The increasing interest in using genistein for treatment and prevention of diseases such as cancer, osteoporosis, cardiovascular diseases, relief of menopause symptoms, among others. As well as the increasing consumption of soy in Western populations as a substitute for animal protein and its use to produce food for infants are worrisome factors because the effects of phytoestrogens on the human organism are still a matter of intense debate. Animal studies are contradictory and human studies are scarce. The aim of the present study was to evaluate genistein safety on human Sertoli cells (hSCs) in vitro. These cells are pivotal for successful espermatogenesis since they provide nutritional and physical support to sperm germ cells. Biopsies from six patients, with conserved espermatogenesis, were chosen at an infertility clinic and primary cultures of human Sertoli cells were cultured and maintained until reaching confluence. Then they were treated with different genistein concentrations during 24h. Different citotoxicity test were perfomed. No disturbances were found in hSCs treated with genistein. Therefore, we conclude that this compound is not cytotoxic to these cells. Subsequently, the analysis of one of the most relevant metabolic pathways, glycolysis, in these cells was made, which originates pyruvate, that in turn, later, is used for the production of lactate. This substrate is an important energy source for germ cells. However, the absorption and excretion of different metabolites of this pathway, in addition to the enzymatic activity of lactate dehydrogenase, did not show significant variations after exposure of hSCs to genistein. Also genistein influence on oxidative stress rates in hSCs was evaluated, since reactive oxigene species (ROS) production is common during cell metabolism and if not eliminated efficiently it can cause irreversible damage on different cell structures and may even lead to cell death. The results of this study demonstrate that genistein did not influence oxidative stress rates. Alltoghether, we can conclude that no harmfull effects, on the parameters analyzed, were caused by genistein on hSCs. Altough it does not mean that genistein, and other phytoestrogens, are safe for the remaining of the reproductive system more studies regarding this subject are needed for a better understanding of their mechanisms of action.
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spelling Is Genistein a Threat to Male Reproductive Potential?Infertilidade masculinaEspermatogéneseGenisteinaGenistein is one of the most abundant phytoestrogens in soybeans. Because of its chemical similarity to endogenous estrogens, genistein can bind to estrogen receptors (ERs) present in cells and mediate an estrogenic response. Its estrogenic action may potentially interfere with normal functioning of various systems in the human organism, including the reproductive system which is highly regulated by sex hormones. The increasing interest in using genistein for treatment and prevention of diseases such as cancer, osteoporosis, cardiovascular diseases, relief of menopause symptoms, among others. As well as the increasing consumption of soy in Western populations as a substitute for animal protein and its use to produce food for infants are worrisome factors because the effects of phytoestrogens on the human organism are still a matter of intense debate. Animal studies are contradictory and human studies are scarce. The aim of the present study was to evaluate genistein safety on human Sertoli cells (hSCs) in vitro. These cells are pivotal for successful espermatogenesis since they provide nutritional and physical support to sperm germ cells. Biopsies from six patients, with conserved espermatogenesis, were chosen at an infertility clinic and primary cultures of human Sertoli cells were cultured and maintained until reaching confluence. Then they were treated with different genistein concentrations during 24h. Different citotoxicity test were perfomed. No disturbances were found in hSCs treated with genistein. Therefore, we conclude that this compound is not cytotoxic to these cells. Subsequently, the analysis of one of the most relevant metabolic pathways, glycolysis, in these cells was made, which originates pyruvate, that in turn, later, is used for the production of lactate. This substrate is an important energy source for germ cells. However, the absorption and excretion of different metabolites of this pathway, in addition to the enzymatic activity of lactate dehydrogenase, did not show significant variations after exposure of hSCs to genistein. Also genistein influence on oxidative stress rates in hSCs was evaluated, since reactive oxigene species (ROS) production is common during cell metabolism and if not eliminated efficiently it can cause irreversible damage on different cell structures and may even lead to cell death. The results of this study demonstrate that genistein did not influence oxidative stress rates. Alltoghether, we can conclude that no harmfull effects, on the parameters analyzed, were caused by genistein on hSCs. Altough it does not mean that genistein, and other phytoestrogens, are safe for the remaining of the reproductive system more studies regarding this subject are needed for a better understanding of their mechanisms of action.A genisteína é um dos fitoestrogénios mais abundantes na soja. Devido à sua similaridade química com os estrogénios endógenos, a genisteína pode se ligar aos receptores de estrogénio (ERs) presente nas células e desencadear uma resposta estrogénica. A sua ação estrogénica pode potencialmente interferir com o funcionamento normal de vários sistemas no organismo humano, incluindo o sistema reprodutivo que é altamente regulado pelas hormonas sexuais. Tem-se verificado um crescente interesse em usar genisteína para tratamento e prevenção de doenças como o cancro, osteoporose, doenças cardiovasculares, alívio dos sintomas de menopausa, entre outros. Há ainda um o aumento do consumo de soja em populações ocidentais, como substituto da proteína animal e é usado para produzir alimentos para bebés sendo fatores preocupantes porque os efeitos dos fitoestrogénios no organismo humano ainda estão sob discussão. Por outro lado, estudos animais são contraditórios e estudos humanos são escassos. No presente estudo avaliou-se a ação da genisteína em células de Sertoli humanas (hSCs). Essas células são fundamentais para uma espermatogênese correta, uma vez que proporcionam suporte físico e nutricional às células germinativas. Biópsias de seis pacientes com espermatogênese conservada, foram recolhidas numa clínica de tratamento de fertilidade e culturas primárias de células de Sertoli humanas foram semeadas e mantidas até atingirem confluência. Atingida essa condição, as células foram tratadas com meios contendo diferentes concentrações de genisteína, durante 24h. Foram realizados diversos testes de citotoxicidade. Não foram detectadas alterações nas hSCs tratadas com genisteína. Conclui-se então que este composto não é tóxico para estas células. Posteriormente, efetuou-se a análise de uma das vias metabólicas mais relevantes nestas células, a glicólise, que origina piruvato que posteriormente é utilizado para a produção de lactato. Esse substrato é uma importante fonte energética para células germinativas. No entanto, a absorção e excreção de diferentes metabolitos desta via, além da atividade enzimática da lactato desidrogenase, não mostraram variações significativas após a exposição das hSCs a genisteína. Também se avaliou a influência da genisteína nas taxas de stress oxidativo em hSCs, uma vez que a produção de espécies reactivas de oxigénio é comum durante o metabolismo celular e, quando não são eficientemente eliminadas, podem causar danos irreversíveis em diferentes estruturas celulares podendo até levar à morte celular. Os resultados do presente estudo demonstram que a genisteína não influenciou as taxas de stress oxidativo. Em suma, conclui-se que não foram identificados efeitos nocivos por parte da genisteína sobre os parametros analisados nas hSCs. No entanto, isso não significa que a genisteína, e outros fitoestrogénios, sejam seguros para o resto do sistema reprodutivo. Por esta razão deverão ser efetuados vários estudos no futuro para o esclarecimento mais amplo da sua ação.Universidade de Aveiro2019-12-06T00:00:00Z2017-12-12T00:00:00Z2017-12-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/21954TID:201940604engYashechkina, Tatianainfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-06T04:12:08Zoai:ria.ua.pt:10773/21954Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T14:00:32.942680Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Is Genistein a Threat to Male Reproductive Potential?
title Is Genistein a Threat to Male Reproductive Potential?
spellingShingle Is Genistein a Threat to Male Reproductive Potential?
Yashechkina, Tatiana
Infertilidade masculina
Espermatogénese
Genisteina
title_short Is Genistein a Threat to Male Reproductive Potential?
title_full Is Genistein a Threat to Male Reproductive Potential?
title_fullStr Is Genistein a Threat to Male Reproductive Potential?
title_full_unstemmed Is Genistein a Threat to Male Reproductive Potential?
title_sort Is Genistein a Threat to Male Reproductive Potential?
author Yashechkina, Tatiana
author_facet Yashechkina, Tatiana
author_role author
dc.contributor.author.fl_str_mv Yashechkina, Tatiana
dc.subject.por.fl_str_mv Infertilidade masculina
Espermatogénese
Genisteina
topic Infertilidade masculina
Espermatogénese
Genisteina
description Genistein is one of the most abundant phytoestrogens in soybeans. Because of its chemical similarity to endogenous estrogens, genistein can bind to estrogen receptors (ERs) present in cells and mediate an estrogenic response. Its estrogenic action may potentially interfere with normal functioning of various systems in the human organism, including the reproductive system which is highly regulated by sex hormones. The increasing interest in using genistein for treatment and prevention of diseases such as cancer, osteoporosis, cardiovascular diseases, relief of menopause symptoms, among others. As well as the increasing consumption of soy in Western populations as a substitute for animal protein and its use to produce food for infants are worrisome factors because the effects of phytoestrogens on the human organism are still a matter of intense debate. Animal studies are contradictory and human studies are scarce. The aim of the present study was to evaluate genistein safety on human Sertoli cells (hSCs) in vitro. These cells are pivotal for successful espermatogenesis since they provide nutritional and physical support to sperm germ cells. Biopsies from six patients, with conserved espermatogenesis, were chosen at an infertility clinic and primary cultures of human Sertoli cells were cultured and maintained until reaching confluence. Then they were treated with different genistein concentrations during 24h. Different citotoxicity test were perfomed. No disturbances were found in hSCs treated with genistein. Therefore, we conclude that this compound is not cytotoxic to these cells. Subsequently, the analysis of one of the most relevant metabolic pathways, glycolysis, in these cells was made, which originates pyruvate, that in turn, later, is used for the production of lactate. This substrate is an important energy source for germ cells. However, the absorption and excretion of different metabolites of this pathway, in addition to the enzymatic activity of lactate dehydrogenase, did not show significant variations after exposure of hSCs to genistein. Also genistein influence on oxidative stress rates in hSCs was evaluated, since reactive oxigene species (ROS) production is common during cell metabolism and if not eliminated efficiently it can cause irreversible damage on different cell structures and may even lead to cell death. The results of this study demonstrate that genistein did not influence oxidative stress rates. Alltoghether, we can conclude that no harmfull effects, on the parameters analyzed, were caused by genistein on hSCs. Altough it does not mean that genistein, and other phytoestrogens, are safe for the remaining of the reproductive system more studies regarding this subject are needed for a better understanding of their mechanisms of action.
publishDate 2017
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2017-12-12
2019-12-06T00:00:00Z
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