Kim Suel-Kee, Kim Jong-Hoon, Han Jung Ho, Yoon Yong-Dal
Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Int J Toxicol. 2008 Mar-Apr;27(2):175-82. doi: 10.1080/10915810801977906.
Tributyltin (TBT) is known to disrupt the development of reproductive organs, thereby reducing fertility. The aim of this study was to evaluate the acute toxicity of TBT on the testicular development and steroid hormone production. Immature (3-week-old) male mice were given a single administration of 25, 50, or 100 mg/kg of TBT by oral gavage. Lumen formation in seminiferous tubule was remarkably delayed, and the number of apoptotic germ cells found inside the tubules was increased in the TBT-exposed animals, whereas no apoptotic signal was observed in interstitial Leydig cells. Reduced serum testosterone concentration and down-regulated expressions of the mRNAs for cholesterol side-chain cleavage enzyme (P450scc), 17alpha -hydroxylase/C(17-20) lyase (P450(17alpha)), 3beta -hydroxysteroid-dehydrogenase (3beta -HSD), and 17beta -hydroxysteroid-dehydrogenase (17beta -HSD) were also observed after TBT exposure. Altogether, these findings demonstrate that exposure to TBT is associated with induced apoptosis of testicular germ cells and inhibition of steroidogenesis by reduction in the expression of steroidogenic enzymes in interstitial Leydig cells. These adverse effects of TBT would cause serious defects in testicular development and function.
已知三丁基锡(TBT)会干扰生殖器官的发育,从而降低生育能力。本研究的目的是评估TBT对睾丸发育和类固醇激素产生的急性毒性。对未成熟(3周龄)雄性小鼠经口灌胃单次给予25、50或100 mg/kg的TBT。在TBT暴露组动物中,生精小管中的管腔形成明显延迟,且在小管内发现的凋亡生殖细胞数量增加,而在间质中的睾丸间质细胞未观察到凋亡信号。TBT暴露后还观察到血清睾酮浓度降低以及胆固醇侧链裂解酶(P450scc)、17α-羟化酶/C(17-20)裂解酶(P450(17α))、3β-羟基类固醇脱氢酶(3β-HSD)和17β-羟基类固醇脱氢酶(17β-HSD)的mRNA表达下调。总之,这些发现表明,暴露于TBT与睾丸生殖细胞凋亡增加以及间质睾丸间质细胞中类固醇生成酶表达降低导致的类固醇生成抑制有关。TBT的这些不良反应会导致睾丸发育和功能出现严重缺陷。