Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes
Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes
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DOI：
10.1006/taap.1996.0055
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发表时间：
1996-03-01
影响因子：
3.8
通讯作者：
Boekelheide, K
中科院分区：
文献类型：
--
作者：
Richburg, JH;Boekelheide, K
邻苯二甲酸单(2-乙基己基)酯(MEHP)是一种被广泛研究的支持细胞毒物。本文报道了28日龄Fischer幼鼠经MEHP(2g/kg，po)染毒后0、3、6、12小时处死后，支持细胞波形细丝分布和睾丸生殖细胞凋亡率的变化。MEHP暴露3小时后，可观察到波形蛋白细丝的崩解，而支持细胞、微管蛋白或肌动蛋白的形态没有改变。从暴露后6小时到12小时，波形蛋白细丝的核周凝聚逐渐增加。为了评估这些支持细胞变化对生殖细胞的影响，研究了细胞凋亡在MEHP诱导的睾丸毒性中的作用。从染毒后6小时和12小时的大鼠睾丸中提取的DNA显示，由于核小体间切割而导致的低分子DNA显着增加。此外，末端脱氧核苷酸转移酶介导的地高辛标记缺口末端标记(TUNEL)染色显示，冰冻睾丸切片中的DNA片段化显示，从MEHP暴露后6至12小时，生殖细胞的凋亡率逐渐增加。然而，在MEHP暴露3小时后，与对照组相比，TUNEL阳性生殖细胞的发生率显著降低。综上所述，支持细胞波形蛋白细丝的早期崩溃和生殖细胞凋亡的同时减少，提示MEHP导致支持细胞功能障碍，导致生殖细胞凋亡的生理机制被破坏。(C)1996年学术出版社。
Mono-(2-ethylhexyl) phthalate (MEHP) is a widely studied Sertoli cell toxicant. Here we describe alterations in Sertoli cell vimentin filament distribution and the incidence of testicular germ cell apoptosis in young (28-day-old) Fischer rats that were treated with MEHP (2 g/kg, po) and killed 0, 3, 6, or 12 hr after exposure. A collapse in vimentin filaments was observed 3 hr after MEHP exposure without accompanying changes in the pattern of Sertoli cell tubulin or actin. A progressive increase in the perinuclear condensation of the vimentin filaments was observed from 6 to 12 hr after exposure. To evaluate the consequences of these Sertoli cell changes on germ cells, the role of apoptosis in MEHP-induced testicular toxicity was examined. DNA isolated from testis of rats 6 and 12 hr after MEHP exposure showed a marked increase in low-molecular-weight DNA resulting from internucleosomal cleavage. In addition, DNA fragmentation visualized in frozen testis cross sections by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end label (TUNEL) staining demonstrated a progressive increase in germ cell apoptosis from 6 to 12 hr after MEHP exposure. However, 3 hr after MEHP exposure, the incidence of TUNEL-positive germ cells was significantly decreased compared to that seen in controls. Taken together, the early collapse in Sertoli cell vimentin filaments and the concurrent decrease in germ cell apoptosis suggests that MEHP engenders Sertoli cell dysfunction resulting in the disruption of the physiological mechanism of germ cell apoptosis. (C) 1996 Academic Press, Inc.