Huang Xiande, Ma Taoye, Yin Yongsheng
Department of Urology, Gansu Provincial Hospital, Lanzhou, China.
Department of Urology, Second Provincial People's Hospital of Gansu, Lanzhou, China.
Front Pharmacol. 2018 Nov 30;9:1320. doi: 10.3389/fphar.2018.01320. eCollection 2018.
Dibutyltin dichloride (DBTCl), widely used as plastic stabilizer, can cause comprehensive toxicity. The present study aims to investigate the effects of DBTCl on rat Leydig cell developmental regeneration and characterize the related mechanism. Adult male Sprague Dawley rats were randomly divided into four groups and gavaged with saline (control) or 5, 10, or 20 mg/kg/day of DBTCl consecutively for 10 days. At the end of the DBTCl treatment, all rats received a single intraperitoneal injection (i.p.,) of 75 mg/kg ethane dimethane sulfonate (EDS) to eliminate all the adult Leydig cells and to induce Leydig cell developmental regeneration. Leydig cell developmental regeneration was evaluated by measuring the levels of serum testosterone, luteinizing hormone, and follicle-stimulating hormone on days 7, 35, and 56 post-EDS. Leydig cell gene and protein expression levels, as well as cell morphology and cell counts were also carried out on day 56 post-EDS. The present study found that DBTCl significantly reduced serum testosterone levels on days 35 and 56 post-EDS, but increased serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels on day 56 at ≥ 5 mg/kg/day. The mRNA and protein levels of Leydig (, and ) and Sertoli cells (, and ) were significantly downregulated in the DBTCl-treated testes compared to the control. Immunohistochemical staining showed that DBTCl-treatment caused fewer regenerated Leydig cells and impaired Sertoli cell development and function in the testis on day 56 post-EDS. In conclusion, the present study demonstrates that DBTCl retards rat Leydig cell developmental regeneration by downregulating steroidogenesis-related enzymes at the gene and protein levels, inhibiting Leydig cell proliferation and impairing Sertoli cell function and development.
二氯化二丁基锡（DBTCl）作为塑料稳定剂被广泛使用，可导致综合毒性。本研究旨在探讨DBTCl对大鼠睾丸间质细胞发育再生的影响，并阐明其相关机制。成年雄性Sprague Dawley大鼠随机分为四组，连续10天分别灌胃生理盐水（对照组）或5、10或20 mg/kg/天的DBTCl。在DBTCl处理结束时，所有大鼠均腹腔注射（i.p.）75 mg/kg乙烷二甲磺酸盐（EDS）以消除所有成年睾丸间质细胞并诱导睾丸间质细胞发育再生。在EDS处理后的第7、35和56天，通过检测血清睾酮、黄体生成素和卵泡刺激素水平来评估睾丸间质细胞的发育再生情况。在EDS处理后的第56天，还检测了睾丸间质细胞的基因和蛋白表达水平，以及细胞形态和细胞计数。本研究发现，DBTCl显著降低了EDS处理后第35和56天的血清睾酮水平，但在≥5 mg/kg/天剂量下，DBTCl在第56天增加了血清黄体生成素（LH）和卵泡刺激素（FSH）水平。与对照组相比，DBTCl处理的睾丸中睾丸间质细胞（、和）和支持细胞（、和）的mRNA和蛋白水平显著下调。免疫组织化学染色显示，在EDS处理后的第56天，DBTCl处理导致再生的睾丸间质细胞减少，并损害了睾丸中支持细胞的发育和功能。总之，本研究表明，DBTCl通过在基因和蛋白水平下调类固醇生成相关酶，抑制睾丸间质细胞增殖，损害支持细胞功能和发育，从而延缓大鼠睾丸间质细胞的发育再生。
