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围生期暴露于双酚 A 和 17-β 雌二醇后雌性甾体激素反应腺中的炎症反应。

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17-β estradiol.

机构信息

Department of Biology, Humanities, and Exact Sciences, Institute of Biosciences, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.

Department of Histology, Embriology, and Cell Biology, Institute of Biological Sciences (ICB III), Federal University of Goiás (UFG), Goiânia, Goiás, Brazil.

出版信息

Cell Biol Int. 2021 Nov;45(11):2264-2274. doi: 10.1002/cbin.11665. Epub 2021 Aug 1.

Abstract

The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-β estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.

摘要

乳腺(MG)和女性前列腺是对激素高度敏感的具有可塑性的生殖器官。因此,内分泌干扰物,如双酚 A(BPA)和外源性雌激素,会对腺体的稳态产生负面影响。除了先前描述的改变外,炎症标志物表达的变化也会引发微环境的改变,从而促进肿瘤的进展。本研究旨在评估 MG 和前列腺在围生期易感性窗口中暴露于 BPA(50μg/kg)和 17-β雌二醇(35μg/kg)时的炎症反应。结果显示,在 6 个月大时,经 BPA 每日 50μg/kg 围生期暴露的雌性前列腺中磷酸化 STAT3(P-STAT3)阳性细胞的数量增加。此外,与未暴露的动物相比,这些动物的巨噬细胞数量增加,这可以通过 F4/80 标志物来证明。尽管乳腺的小叶腺泡和导管内增生的发生率增加,但在评估的四个炎症标志物(肿瘤坏死因子-α、COX-2、P-STAT3 和 F4/80)的表达上,MG 并未显示出任何差异。对同一动物的两个腺体进行分析的结果表明,在围生期易感性窗口中暴露于内分泌干扰物会导致不同生殖器官产生不同的炎症反应。由于前列腺对这些炎症机制更敏感,因此可以肯定的是,该器官的可能肿瘤改变与基质炎症模式的变化有关,而这种特征在 MG 中并不明显。

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