Estrogen agonists, 17β-estradiol, bisphenol A, and diethylstilbestrol, decrease cortactin expression in the mouse testis
Estrogen agonists, 17β-estradiol, bisphenol A, and diethylstilbestrol, decrease cortactin expression in the mouse testis
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DOI：
10.1679/aohc.69.101
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发表时间：
2006-06-01
影响因子：
--
通讯作者：
Mori, Chisato
中科院分区：
文献类型：
--
作者：
Anaharal, Reiko;Yoshida, Miyo;Mori, Chisato
以往的报道表明，雌激素激动剂或抗雄激素化学物质会导致啮齿类动物异常生精。在生精上皮中，顶端胞质特化(ES)是一种在支持细胞和精子细胞之间发育的以肌动蛋白为基础的(细胞-细胞)连接结构，基础ES也是如此，尽管它位于相邻的支持细胞之间。在顶端和底部的ES中有几种控制精子细胞发育过程的黏附复合体蛋白。Cortactin是一种肌动蛋白结合蛋白，是ES黏附蛋白的一种，与多种细胞间黏附相关蛋白结合。本研究对12周龄ICR雄性小鼠皮下注射17β-雌二醇(E_2，1.2mU/kg)、双酚A(BPA，2.4mU/kg)和己烯雌酚(DES，2.5mU/kg)。通过Western印迹分析、免疫组织化学分析和免疫电子显微镜分析，观察E_2、BPA和DES对小鼠睾丸皮质蛋白表达的影响。观察表明，处理后的睾丸免疫反应性明显降低。治疗组大鼠睾丸顶端ES区皮质蛋白免疫组织化学反应性降低。免疫电子显微镜观察显示，雌二醇组和双酚A组大鼠顶端ES区皮质蛋白的免疫定位均较对照组减少，DES组顶端和基底区ES区免疫金颗粒明显减少。在毒理学领域，Cortactin可能被认为是精子发生异常的指示蛋白之一，受外源性化学物质的影响，如内分泌干扰化学物质。综上所述，这项研究有助于理解外源性激素化学处理导致精子发生的组织学异常的皮质素蛋白表达。
Previous reports have revealed that estrogen agonists or anti-androgenic chemicals induce abnormal spermiogenesis in rodents. In the seminiferous epithelium, the apical ectoplasmic specialization (ES) is an actin-based (cell-cell) junctional structure developing between the Sertoli cells and spermatids as is the basal ES also although it is located between adjoining Sertoli cells. In the apical and basal ES are several adhesion complex proteins that control the spermatid developing process. Cortactin, an actin-binding protein, is one of the ES adhesion proteins, combining with several cell-cell adhesions associating proteins. In the present study, 17 beta-estradiol (E2, 1.2,mu g/kg), bisphenol A (BPA, 2.4 mu g/kg), and diethylstilbestrol (DES, 2.5 mu g/kg) were subcutaneously injected in ICR 12-week-old male mice. Mice testes were observed for the expression of cortactin protein after E2, BPA, and DES treatments by Western blot analysis, immunohistochemical analysis, and immuno-electron microscopic analysis. Observations showed that the immunoreactivity of the treated testes was significantly decreased. The immunohistochemical reactivity of cortactin in the apical ES was decreased in the treated testis. In immunoelectron microscopic observations, ultrastructural immunolocalizations of cortactin protein in the apical ES by both E2 and BPA were decreased, and the immuno-gold particles of apical and basal ES by DES were much less than the control. In the toxicological field, cortactin may be considered to be one of the indicator proteins of abnormal spermiogenesis which is affected by exogenous chemicals, such as endocrine disrupting chemicals. In summary, this study helps toward understanding the cortactin protein expression underlying the histological abnormalities of spermatogenesis induced by exogenous hormonal chemical treatment.