Efeitos do propil-parabeno e butil-parabeno na atividade reprodutiva de ratas wistar adultas
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2020-04-24
Autores
Brochine, Suzane
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Universidade Estadual Paulista (Unesp)
Resumo
As substâncias desreguladores endócrinas de diversas origens e propriedades químicas acomentem uma diversidade de mamíferos, animais silvestres e seres humanos, que podem interagir com o sistema reprodutivo feminino e prejudicar a homeostase hormonal. Dentro dessa classificação, os parabenos podem ser utilizados como conservantes em diversos produtos comerciais. Seus efeitos se tornam cada vez mais complexos em relação à idade, história reprodutiva, ambiente endócrino da espécime no momento da exposição, como também não é sabido todos os reais mecanismos desses compostos quando associados. Sendo assim, o objetivo deste estudo foi avaliar os efeitos dos parabenos em ratas Wistar durante um período de 90 dias consecutivos de exposição. Assim, as ratas foram distribuídas em quatro grupos experimentais: controle, que recebeu somente óleo de milho como veículo, e tratados com propil e buti-parabeno nas doses de 10 mg/kg, 100 mg/kg, ou 200 mg/kg e expostas via subcutânea. Foi utilizada a técnica de citologia vaginal para investigar a ciclicidade das fêmeas, bem como a caracterização das fases do ciclo estral pelo método Shorr. Além desses parâmetros, foram analisados aspectos morfológicos de ovários e útero, quantificação das estruturas ovarianas e avaliação ultraestutural de folículos pré-ovulatórios. Foram avaliados a concentração plasmática de estrógeno, peso corporal bem como o peso dos órgãos reprodutivos. Os resultados revelaram que o método Shorr, foi eficaz para identificar e caracterizar os tipos celulares encontrados no epitélio vaginal como a identificação de cada fase do ciclo estral. Além disso, o peso absoluto e relativo dos órgãos reprodutivos não apresentou diferença entre os grupos experimentais. A análise histológica dos ovários revelou que, todos os estágios foliculares permaneceram inalterados, como também a classificação morfológica dos Complexos Cumulus oophurus coletados. Porém, houve diminuição significativa de folículos totais primordiais e primários em fêmeas que receberam 10 e 200 mg/kg. Quanto aos folículos atrésicos houve maior incidência no grupo de 100mg/Kg. A avaliação ultraestrutural de folículos pré-ovulatórios confirmou a análise morfológica, pois permaneceram saudáveis, sem alterações a nível celular. A partir da avaliação histopatológica do útero, infiltrados leucocitários não apresentaram diferença nas proporções de células mononucleadas e polimorfonucleadas, como a intensidade. Os parâmetros histomorfométricos do tecido uterino não foram alterados como também a expressão de receptores estrogênicos (REα) no tecido uterino e ovariano. A intensidade de marcação dos receptores de progesterona no útero apresentaram diminuídas nas doses de 10 e 100 mg/Kg, e no tecido ovariano apenas a dose 100 mg/Kg. A partir dos parâmetros avaliados no presente estudo, sugere-se que após a exposição prolongada dos compostos de parabeno, a funcionalidade dos tecidos reprodutivos em fêmeas adultas pode ter sido prejudicada. Apesar da morfologia e estrutura dos órgãos sexuais permanecerem inalterados, mais estudos a nível celular e molecular precisam ser realizados para melhor entendimento da atuação conjunta dessas substâncias.
The endocrine disruption substances of many origins and chemistry properties affect a diversity of mammals, wild animals and human beings. These substances can interact with the female reproductive system and damage the hormonal homeostasis. In this classification, the paraben could be used as preservatives in different commercial products. Its effects get even worst and complex with the age, reproductive history, and endocrine environment of the specie in the moment of exposure of the drug. In complement, it is not known the actual mechanisms of those compounds when they are associated. Thus, the goal of this experiment was evaluate the effects of parabens in females Wistar during 90 consecutive days of exposure. Therefore, the females were divided in four experimental groups: Control group – Corn oil; and a mixture of propil and butyl paraben with 10 mg/kg, 100 mg/kg and 200 mg/kg and exposed through the subcutaneous pathway. The vaginal cytology was performed to investigate the cyclicality as well as the characterization of the estrous phases by the Shor method. Besides that, morphological aspects of the ovary and uterus, counting of ovaries structure and ultrastructural of pre-ovulatory follicle. To complete the evaluation, the plasmatic estrogen, body weight and reproductive organ weight were assessed. The Shor method was effective to characterize and identify the cells types of the vaginal epithelium and identify the estrous cycle phase. Moreover, the relative and absolute weight have shown no difference between the experimental groups. The follicle stages had no alteration, as well as the morphological evaluating of the Cumulus oophurus by the histological analyses of the ovaries. However, there was decrease of primordial and primary follicles in females treated with 10 and 200 mg/kg. The ultrastructural evaluation of the pre-ovulatory follicles has shown no difference, confirming the morphological evaluation, with no cellular level alteration. From the histopathology evaluation, there was no difference in leukocytes infiltrates have not shown difference on proportions of mononucleated and polymorphonuclear cells, such as the intensity. No differences in the uterine tissue and expression of the estrogenic receptors were found. Regarding the progesterone receptors, there was a decrease of the expression in the uterus to the 10 and 100 mg/kg treatments, and to the 100 mg/kg dosage in the ovarian tissue. From the parameters evaluated in the present study, it is suggested that after the long exposure to the parabens, the function of the reproductive systems could be damaged. Although the morphology and the structure of the reproductive systems had no alteration, more molecular and cellular studies must be performed to the completely understand the action of these substances in association.
The endocrine disruption substances of many origins and chemistry properties affect a diversity of mammals, wild animals and human beings. These substances can interact with the female reproductive system and damage the hormonal homeostasis. In this classification, the paraben could be used as preservatives in different commercial products. Its effects get even worst and complex with the age, reproductive history, and endocrine environment of the specie in the moment of exposure of the drug. In complement, it is not known the actual mechanisms of those compounds when they are associated. Thus, the goal of this experiment was evaluate the effects of parabens in females Wistar during 90 consecutive days of exposure. Therefore, the females were divided in four experimental groups: Control group – Corn oil; and a mixture of propil and butyl paraben with 10 mg/kg, 100 mg/kg and 200 mg/kg and exposed through the subcutaneous pathway. The vaginal cytology was performed to investigate the cyclicality as well as the characterization of the estrous phases by the Shor method. Besides that, morphological aspects of the ovary and uterus, counting of ovaries structure and ultrastructural of pre-ovulatory follicle. To complete the evaluation, the plasmatic estrogen, body weight and reproductive organ weight were assessed. The Shor method was effective to characterize and identify the cells types of the vaginal epithelium and identify the estrous cycle phase. Moreover, the relative and absolute weight have shown no difference between the experimental groups. The follicle stages had no alteration, as well as the morphological evaluating of the Cumulus oophurus by the histological analyses of the ovaries. However, there was decrease of primordial and primary follicles in females treated with 10 and 200 mg/kg. The ultrastructural evaluation of the pre-ovulatory follicles has shown no difference, confirming the morphological evaluation, with no cellular level alteration. From the histopathology evaluation, there was no difference in leukocytes infiltrates have not shown difference on proportions of mononucleated and polymorphonuclear cells, such as the intensity. No differences in the uterine tissue and expression of the estrogenic receptors were found. Regarding the progesterone receptors, there was a decrease of the expression in the uterus to the 10 and 100 mg/kg treatments, and to the 100 mg/kg dosage in the ovarian tissue. From the parameters evaluated in the present study, it is suggested that after the long exposure to the parabens, the function of the reproductive systems could be damaged. Although the morphology and the structure of the reproductive systems had no alteration, more molecular and cellular studies must be performed to the completely understand the action of these substances in association.
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Palavras-chave
Parabeno, Desenvolvimento folicular, Ciclo estral, Sistema reprodutor de fêmeas., Estrous cycle, Female reproductive system, Follicular development, Paraben