Chronic high dose intraperitoneal bisphenol A (BPA) induces substantial histological and gene expression alterations in rat penile tissue without impairing erectile function.
Chronic high dose intraperitoneal bisphenol A (BPA) induces substantial histological and gene expression alterations in rat penile tissue without impairing erectile function.
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DOI：
10.1111/jsm.12336
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Gonzalez-Cadavid NF
中科院分区：
文献类型：
--
作者：
Kovanecz I;Gelfand R;Masouminia M;Gharib S;Segura D;Vernet D;Rajfer J;Li DK;Liao CY;Kannan K;Gonzalez-Cadavid NF
双酚A（BPA），从塑料和牙科密封剂中释放出来，是一种可疑的内分泌干扰物和生殖毒物。在职业暴露的工人中，BPA与勃起功能障碍（艾德）有关。为了确定大鼠长期暴露于高剂量BPA是否会影响睾酮（T）和雌二醇（E2）的血清水平，并诱导身体组织病理学和由此产生的ED。每天向幼龄大鼠腹膜内（IP）注射25 mg/kg/天BPA或溶剂（n = 8/组）。在3个月时通过阴茎海绵体测量和电场刺激（EFS）测量勃起功能。测定血清、尿液和阴茎组织中的BPA，并测定血清T和E2。对阴茎组织切片进行定量Masson三色染色、末端脱氧核苷酸转移酶dUTP缺口末端标记、油红O、钙调蛋白、α-平滑肌肌动蛋白的免疫组化以及Oct 4。蛋白质标记物通过Western印迹和2-D微凝胶进行评估，RNA通过DNA微阵列进行评估。勃起功能、组织学和身体组织的生化标志物。在BPA处理的大鼠中，血清、尿液和阴茎组织中的总BPA和游离BPA水平升高，而血清T和E2水平降低。此外，海绵体显示平滑肌（SM）含量、SM/胶原蛋白比例降低，肌成纤维细胞、脂肪沉积和细胞凋亡增加，但胶原蛋白含量或干细胞（核/核周）无显著变化。在阴茎干中，BPA诱导Nanog（干细胞）、神经元型一氧化氮合酶（氮能末梢）和血管内皮生长因子（血管生成）下调，与SM张力和细胞骨架相关的基因上调5- 50倍，伴随着多种蛋白质谱的变化。然而，海绵体测量和EFS均未被BPA改变。虽然长期接受高IP剂量BPA治疗的大鼠出现性腺功能减退症和通常与艾德相关的组织病理学和分子病理学，但通过EFS和海绵体测量法测得的勃起功能未检测到变化。需要进一步研究使用不同剂量和暴露时间的BPA给药替代途径来扩大这些发现。Kovanecz I，Gelfand R，Masouminia M，Gharib S，塞古拉D，Vernet D，Rajfer J，Li DK，Liao CY，Kannan K，and Gonzalez-Cadavid NF.慢性高剂量腹腔内双酚A（BPA）诱导大鼠阴茎组织的组织学和基因表达的变化，而不损害勃起功能。
Bisphenol A (BPA), released from plastics and dental sealants, is a suspected endocrine disruptor and reproductive toxicant. In occupationally exposed workers, BPA has been associated with erectile dysfunction (ED). To determine whether long-term exposure to high doses of BPA in the rat affects serum levels of testosterone (T) and estradiol (E2), and induces corporal histopathology and resultant ED. Young rats were injected intraperitoneal (IP) injection daily with BPA at 25 mg/kg/day or vehicle (n = 8/group). Erectile function was measured at 3 months by cavernosometry and electrical field stimulation (EFS). BPA was assayed in serum, urine, and penile tissue, and serum T and E2 were determined. Quantitative Masson trichrome, terminal deoxynucleotidyl transferase dUTP nick end labeling, Oil Red O, immunohistochemistry for calponin, α-smooth muscle actin, and Oct 4 were applied to penile tissue sections. Protein markers were assessed by Western blots and 2–D minigels, and RNA by DNA microarrays. Erectile function, histological, and biochemical markers in corporal tissue. In the BPA-treated rats, total and free BPA levels were increased in the serum, urine, and penile tissue while serum T and E2 levels were reduced. In addition, the corpora cavernosa demonstrated a reduction in smooth muscle (SM) content, SM/collagen ratio, together with an increase in myofibroblasts, fat deposits, and apoptosis, but no significant change in collagen content or stem cells (nuclear/perinuclear Oct 4). In the penile shaft, BPA induced a downregulation of Nanog (stem cells), neuronal nitric oxide synthase (nitrergic terminals), and vascular endothelial growth factor (angiogenesis), with genes related to SM tone and cytoskeleton upregulated 5- to 50-fold, accompanied by changes in the multiple protein profile. However, both cavernosometry and EFS were unaltered by BPA. While rats treated chronically with a high IP dose of BPA developed hypogonadism and a corporal histo- and molecular-pathology usually associated with ED, no changes were detected in erectile function as measured by EFS and cavernosometry. Further studies using alternate routes of BPA administration with various doses and length of exposure are needed to expand these findings. Kovanecz I, Gelfand R, Masouminia M, Gharib S, Segura D, Vernet D, Rajfer J, Li DK, Liao CY, Kannan K, and Gonzalez-Cadavid NF. Chronic high dose intraperitoneal bisphenol A (BPA) induces substantial histological and gene expression alterations in rat penile tissue without impairing erectile function.
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