Exposição da próstata de fêmeas de gerbilo da Mongólia (Meriones unguiculatus) a doses ambientais de Bisfenol A e 17beta estradiol
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2020-03-04
Autores
Bedolo, Carolina Marques
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Universidade Estadual Paulista (Unesp)
Resumo
A próstata é uma glândula componente do sistema genital dos mamíferos e sua principal função prostática é secretar um fluido levemente alcalino (pH 7,29) que contribui para a formação do líquido seminal. As fêmeas em certas espécies, como o roedor gerbilo da Mongólia (Meriones unguiculatus), apresentam próstata cuja morfologia se assemelha à porção ventral do complexo prostático masculino e à próstata feminina em humanos. Nas últimas décadas tem sido relatado um constante aumento da exposição a substâncias capazes de interferir na ação hormonal, conhecidas como disruptores endócrinos. O bisfenol A (BPA) pertence a uma das categorias de disruptores endócrinos presentes no meio ambiente. Estudos demonstram que a exposição a esse composto interfere negativamente na morfofisiologia prostática, favorecendo o estabelecimento de lesões pré-malignas e malignas. Além do BPA, uma das constantes problemáticas dos dias atuais é a exposição ambiental a hormônios exógenos como o estradiol (E2). Desta forma, a administração de fármacos com estrutura semelhante a hormônios esteroides pode exercer efeitos sobre a glândula, uma vez que os mesmos se ligam a seus receptores hormonais afetando a homeostasia prostática. O presente estudo teve como objetivo verificar as alterações morfofuncionais na próstata de fêmeas de gerbilo da Mongólia após tratamento perinatal com dose diária ambiental, ou seja, dose ambiental segura de BPA (50 µg/kg) e doses de 17-β estradiol (35 µg/kg), 3 vezes por semana por 38 dias. Foram realizadas análises estereológicas, morfométricas, citoquímicas e imunohistoquímicas. As análises morfológicas demonstraram a presença de alterações como focos inflamatórios associados a células claras e neoplasias intraepiteliais prostáticas (PINs) nos grupos E2, BPA e controle óleo (CO) tratados em relação ao grupo controle água (CA). Nas análises imunohistoquímicas, foram observadas a presença de macrófagos e a imunoexpressão de alfa-actina do músculo liso. Além disso, foi observado aumento nos compartimentos lúmen e estroma não muscular do grupo E2 (grupo estradiol) em relação ao grupo BPA e CA. Concluiu-se que os disruptores endócrinos, BPA e E2 interferem na homeostasia prostática em fêmeas, promovendo alterações morfológicas à semelhança do que ocorre em machos. Nosso estudo sugere que a próstata feminina tem relevância clínica e a fêmea do gerbilo é um bom modelo para se avaliar as repercussões morfofisiológicas de disruptores endócrinos sobre essa glândula do trato genital.
The prostate gland is a component of mammals genital system and its main function is to secrete a slightly alkaline fluid (pH 7.29) that contributes to the composition of the seminal fluid. Females in certain rodent species, such as the Mongolian gerbil (Meriones unguiculatus), have a prostate which morphology resembles the ventral portion of the male prostate complex and the female prostate in humans. In the last decades, there has been a constant increase in the exposure to substances capable of interfering with hormonal action, known as endocrine disruptors. Bisphenol A (BPA) belongs to one of the categories of endocrine disruptors present in the environment. Studies show that exposure to this compound negatively interferes with prostate morphophysiology, favoring the establishment of premalignant and malignant lesions. In addition to BPA, one of the current constant issues is the environmental exposure to exogenous hormones such as estradiol (E2). Thus, the exposure to drugs with a structure similar to steroid hormones can exert effects on the glands, since they bind to their hormone receptors, affecting prostatic homeostasis. The present study aimed to verify the morphofunctional changes in the female Mongolian gerbil prostate after perinatal exposure to daily safe environment doses of BPA (50 µg / kg) and doses of 17-β estradiol (35 µg / kg). Stereological, morphometric, cytochemical and immunohistochemical analysis were performed. Morphological analysis showed presence of alterations such as inflammatory foci associated with clear cells and prostatic intraepithelial neoplasms (PINs) in the E2, BPA and oil control (CO) groups in comparison to the water control group (CA). The immunohistochemical analysis showed presence of macrophages and the immunoexpression of alpha-actin. In addition, the non-muscular stromal compartment and lumen of the E2 group increased in comparison to the BPA and CA groups. In conclusion, the endocrine disruptors BPA and estradiol interfere in prostatic homeostasis in females, leading to morphological changes, similarly to what happens in males. Our study suggests that the female prostate has clinical relevance and the female gerbil is a good model for assessing the morphophysiological repercussions of endocrine disruptors on this genital gland.
The prostate gland is a component of mammals genital system and its main function is to secrete a slightly alkaline fluid (pH 7.29) that contributes to the composition of the seminal fluid. Females in certain rodent species, such as the Mongolian gerbil (Meriones unguiculatus), have a prostate which morphology resembles the ventral portion of the male prostate complex and the female prostate in humans. In the last decades, there has been a constant increase in the exposure to substances capable of interfering with hormonal action, known as endocrine disruptors. Bisphenol A (BPA) belongs to one of the categories of endocrine disruptors present in the environment. Studies show that exposure to this compound negatively interferes with prostate morphophysiology, favoring the establishment of premalignant and malignant lesions. In addition to BPA, one of the current constant issues is the environmental exposure to exogenous hormones such as estradiol (E2). Thus, the exposure to drugs with a structure similar to steroid hormones can exert effects on the glands, since they bind to their hormone receptors, affecting prostatic homeostasis. The present study aimed to verify the morphofunctional changes in the female Mongolian gerbil prostate after perinatal exposure to daily safe environment doses of BPA (50 µg / kg) and doses of 17-β estradiol (35 µg / kg). Stereological, morphometric, cytochemical and immunohistochemical analysis were performed. Morphological analysis showed presence of alterations such as inflammatory foci associated with clear cells and prostatic intraepithelial neoplasms (PINs) in the E2, BPA and oil control (CO) groups in comparison to the water control group (CA). The immunohistochemical analysis showed presence of macrophages and the immunoexpression of alpha-actin. In addition, the non-muscular stromal compartment and lumen of the E2 group increased in comparison to the BPA and CA groups. In conclusion, the endocrine disruptors BPA and estradiol interfere in prostatic homeostasis in females, leading to morphological changes, similarly to what happens in males. Our study suggests that the female prostate has clinical relevance and the female gerbil is a good model for assessing the morphophysiological repercussions of endocrine disruptors on this genital gland.
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Palavras-chave
Gerbilo da Mongólia, Bisfenol A, 17beta estradiol, Próstata feminina, Disruptores endócrinos, Mongolian gerbil, Bisphenol A, Female prostate, Endocrine disruptors