Oral Bisphenol A (BPA) given to rats at moderate doses is associated with erectile dysfunction, cavernosal lipofibrosis and alterations of global gene transcription.

Oral Bisphenol A (BPA) given to rats at moderate doses is associated with erectile dysfunction, cavernosal lipofibrosis and alterations of global gene transcription.
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DOI:
10.1038/ijir.2013.37
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发表时间:
2014-03
影响因子:
2.6
通讯作者:
Gonzalez-Cadavid, N. F.
Gonzalez-Cadavid, N. F.
中科院分区:
医学3区
文献类型:
--
作者:
Kovanecz, I.;Gelfand, R.;Masouminia, M.;Gharib, S.;Segura, D.;Vernet, D.;Rajfer, J.;Li, D. K.;Kannan, K.;Gonzalez-Cadavid, N. F.

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双酚A(BPA)是一种疑似生殖生物危害和内分泌干扰物,从塑料中释放出来,与职业暴露工人的勃起功能障碍(艾德)有关。然而,在大鼠中,尽管诱导性腺功能减退,阴茎海绵体平滑肌细胞凋亡,脂肪浸润到海绵体组织,并与高剂量BPA的腹腔内给药的全球基因表达的变化,艾德没有观察到。我们研究了BPA经口给药而不是腹腔给药是否会导致大鼠阴茎组织中的ED、艾德、组织学和生化标志物。2.5-每天给一个月大的大鼠饮用不含和含1和0.1 mg/kg/天BPA的水。两个月后,通过阴茎海绵体测量法(DIC)和电场刺激(EFS)测定勃起功能,并测定血清睾酮(T)、雌二醇(E2)和BPA水平。采用Masson(平滑肌(SM)/胶原)、油红O(脂肪)、TUNEL(凋亡)、Oct 4(干细胞)和α-SM肌动蛋白/钙调蛋白(SM和肌成纤维细胞)的免疫组织化学方法,应用定量图像分析对阴茎组织切片进行分析。其他标志物通过蛋白质印迹法测定。DNA微阵列/microRNA测定定义转录谱。口服BPA不影响体重,但:1)降低血清T和E2; 2)降低EFS反应,增加DIC下降率; 3)增加身体组织中脂肪、肌成纤维细胞和凋亡的存在; 4)降低SM和干细胞的含量,但不影响神经末梢;和5)引起阴茎干内mRNA和microRNA的转录谱的改变。大鼠长期暴露于口服BPA,导致中度的身体静脉闭塞功能障碍(CVOD),可能是由于身体组织内的改变,造成与炎症,纤维化和上皮/间质转化(EMT)相关的基因转录变化。
Bisphenol A (BPA), a suspected reproductive biohazard and endocrine disruptor released from plastics is associated with erectile dysfunction (ED) in occupationally exposed workers. However, in rats, despite the induction of hypogonadism, apoptosis of the penile corporal smooth muscle, fat infiltration into the cavernosal tissue, and changes in global gene expression with the intraperitoneal administration of high dose BPA, ED was not observed. We investigated whether BPA administered orally rather than intraperitoneally to rats for longer periods and lower doses will lead to ED. ED, histological, and biochemical markers in rat penile tissues. 2.5-month old rats were given drinking water daily without and with BPA at 1 and 0.1 mg/kg/day. Two months later, erectile function was determined by cavernosometry (DIC) and electrical field stimulation (EFS) and serum levels of testosterone (T), estradiol (E2), and BPA were measured. Penile tissue sections were assayed by Masson (smooth muscle (SM)/collagen), Oil Red O (fat), TUNEL (apoptosis), immunohistochemistry for Oct 4 (stem cells), and α-SM actin/ calponin (SM and myofibroblasts), applying quantitative image analysis. Other markers were assayed by western blots. DNA microarrays/microRNA assays defined transcription profiles. Orally administered BPA did not affect body weight, but: 1) decreased serum T and E2; 2) reduced the EFS response and increased the DIC drop rate; 3) increased within the corporal tissue the presence of fat, myofibroblasts and apoptosis; 4) lowered the contents of SM and stem cells, but not nerve terminals; and 5) caused alterations of the transcriptional profiles for both mRNA and microRNAs within the penile shaft. Long-term exposure of rats to oral BPA,caused a moderate corporal veno-occlusive dysfunction (CVOD), possibly due to alterations within the corporal tissue that pose gene transcriptional changes related to inflammation, fibrosis and epithelial/ mesenchymal transition (EMT).
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影响因子: --
作者:
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