Jones H B, Garside D A, Liu R, Roberts J C
Safety of Medicines Department, Zeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom.
Exp Mol Pathol. 1993 Jun;58(3):179-93. doi: 10.1006/exmp.1993.1016.
Phthalate esters are widely used in the manufacture of plastics and have been shown to cause testicular toxicity, purportedly, by targeting the Sertoli cell alone. Recent evidence, however, indicates that a paracrine control exists between Sertoli and Leydig cells and the breakdown of one component of this relationship is therefore detrimental to normal function. However, no data that explore the influence of testicular toxins on Leydig cell structure and function have been published hitherto. The preliminary studies reported here were initiated to test the hypothesis that phthalate intoxication may adversely alter Leydig cell structural and functional integrity. Four phthalate esters, namely, di(2-ethylhexyl) phthalate (DEHP, di-n-pentyl phthalate (DPP)., di-n-octyl phthalate (DOP), and diethyl phthalate (DEP) were investigated in vivo and their monoesters (MEHP, MPP, MOP, and MEP, respectively) in vitro for indications of Leydig cell toxicity in the rat. Rats were dosed by oral gavage with 2 g phthalate diester/kg/day in corn oil vehicle for 2 days, while Leydig cell primary cultures were incubated with 1,000 microM monoester for 2 hr. Light and electron microscopy were undertaken to determine the type and degree of any changes. Phthalate esters exerted a direct effect on Leydig cell structure and function (as determined by testosterone output) with correlation of the in vitro and in vivo effects of MEHP (DEHP) and MOP (DOP). No effects on Leydig cell structure or function were seen with MPP (DPP), although Sertoli cell cytoplasmic rarefaction and vacuolation were observed in vivo. DEP produced Leydig cell ultrastructural alterations in vivo. We conclude that individual phthalate esters may exert effects on both Sertoli and Leydig cells or one cell type alone.
邻苯二甲酸酯广泛应用于塑料制造，据称它会单独作用于支持细胞，从而导致睾丸毒性。然而，最近有证据表明，支持细胞和间质细胞之间存在旁分泌控制，因此这种关系中任何一个组成部分的破坏都会对正常功能产生不利影响。然而，迄今为止尚未发表任何探索睾丸毒素对间质细胞结构和功能影响的数据。此处报告的初步研究旨在检验邻苯二甲酸酯中毒可能会对间质细胞结构和功能完整性产生不利改变这一假设。研究了四种邻苯二甲酸酯，即邻苯二甲酸二（2-乙基己基）酯（DEHP）、邻苯二甲酸二正戊酯（DPP）、邻苯二甲酸二正辛酯（DOP）和邻苯二甲酸二乙酯（DEP）在体内的情况，以及它们的单酯（分别为MEHP、MPP、MOP和MEP）在体外对大鼠间质细胞毒性的指示作用。给大鼠经口灌胃2 g邻苯二甲酸二酯/千克/天，溶于玉米油载体中，持续2天，而间质细胞原代培养物则与1000微摩尔单酯孵育2小时。采用光镜和电镜来确定任何变化的类型和程度。邻苯二甲酸酯对间质细胞结构和功能产生直接影响（通过睾酮分泌量来确定），MEHP（DEHP）和MOP（DOP）的体外和体内作用具有相关性。MPP（DPP）对间质细胞结构或功能没有影响，尽管在体内观察到支持细胞胞质疏松和空泡化。DEP在体内引起了间质细胞超微结构改变。我们得出结论，不同邻苯二甲酸酯可能对支持细胞和间质细胞都有影响，或者仅对一种细胞类型有影响。
