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孕期暴露于炔雌醇会改变雄性和雌性沙鼠衰老过程中的形态模式,并增加前列腺病变的易感性。

Prenatal exposure to ethinylestradiol alters the morphologic patterns and increases the predisposition for prostatic lesions in male and female gerbils during ageing.

作者信息

Perez Ana P S, Biancardi Manoel F, Caires Cássia R S, Falleiros-Junior Luiz R, Góes Rejane M, Vilamaior Patricia S L, Santos Fernanda C A, Taboga Sebastião R

机构信息

Department of Structural and Functional Biology, Institute of Biology, University of Campinas -UNICAMP, Campinas, São Paulo, Brazil.

Department of Biology, Institute of Biosciences, Letters and Exact Sciences, São Paulo State University - IBILCE/UNESP, São José do Rio Preto, São Paulo, Brazil.

出版信息

Int J Exp Pathol. 2016 Feb;97(1):5-17. doi: 10.1111/iep.12153. Epub 2016 Feb 8.

Abstract

Ethinylestradiol (EE) is an endocrine disruptor (ED) which acts as an oestrogen agonist; this compound is known as an oral contraceptive. Male and female rodents exposed to EE during critical time points of development, such as in the prenatal period, show alterations in their reproductive tract during adulthood. Few studies have placed an emphasis on the effects of EE during ageing. Thus, this study had as it's objective the analysis of the morphological and immunohistochemical effects of exposure to EE in the prenatal period on ventral male prostate and female prostate of gerbils (Meriones unguiculatus) during ageing. The animals were exposed to EE (15 μg/kg/day) during the 18-22th days of prenatal life (EE/PRE group), and the analyses were performed when the male and female reached 12 months of age. Our results showed an increase in the development of prostatic intraepithelial neoplasia (PIN), which was observed in the male and female prostate of EE/PRE groups. Immunohistochemistry showed a rise in prostatic epithelial and basal cells immunoreactivity, respectively, and to AR and p63 in the male EE/PRE. There were alterations in the morphological pattern of the prostatic glands and increase in predisposition to emergence of prostatic lesions of both sexes during ageing. Despite male and female having been exposed to the same doses of EE, the "exposure to EE promoted modifications" more accentuated in the male prostate. Thus the male gland is more sensitive to the action of this synthetic oestrogen than the female prostate.

摘要

炔雌醇(EE)是一种内分泌干扰物(ED),具有雌激素激动剂的作用;这种化合物是一种口服避孕药。在发育的关键时间点,如孕期,接触EE的雄性和雌性啮齿动物在成年后其生殖道会出现改变。很少有研究关注EE在衰老过程中的影响。因此,本研究的目的是分析孕期接触EE对老年沙土鼠(长爪沙鼠)雄性腹侧前列腺和雌性前列腺的形态学和免疫组化影响。在孕期第18 - 22天,动物接触EE(15μg/kg/天)(EE/PRE组),当雄性和雌性达到12月龄时进行分析。我们的结果显示,EE/PRE组的雄性和雌性前列腺中前列腺上皮内瘤变(PIN)的发生率增加。免疫组化显示,雄性EE/PRE组中前列腺上皮细胞和基底细胞对雄激素受体(AR)和p63的免疫反应性分别升高。在衰老过程中,两性前列腺腺泡的形态模式发生改变,前列腺病变出现的易感性增加。尽管雄性和雌性接触的EE剂量相同,但EE对雄性前列腺的“暴露促进改变”更为明显。因此,雄性腺体比雌性前列腺对这种合成雌激素的作用更敏感。

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