Cadmium과 Di-(2-ethylhexyl) phthalate에 의한 고환 독성: 아연과 Apoptosis의 역할

Abstract

Cadmium (Cd) and di-(2-ethylhexyl) phthalate are used widely and distributed ubiquitously in the environment, which are well-known reproductive toxicants. DEHP and/or Cd causes the apoptosis, degeneration of spermatogenic cells, and massive necrosis, resulting in testicular atrophy. Zinc is an essential metal in spermatogenesis, the zinc concentration in testis is changed in DEHP- or Cd-treated animals. However, the role of zinc or apoptosis in testicular toxicity by DEHP or Cd has not been understood well. In this study, Sprague-Dawley male rats were given DEHP (2 g/kg, 5 ml corn-oil, PO) or Cd (CdCl₂2 mg/kg, 4 ml saline, sc) for 1, 2, 7 and 14 days. Control rats were given vehicle corresponding to each group. At day 1, 2, 7, and 14 after administration of DEHP or Cd, the morphological findings including apoptosis in testes were observed under the light microscope, and the zinc concentrations in testes were determined by atomic absorption spectrometry with flame method. Fas and FasL mRNA in testes were analyzed by RT-PCR method at 12 hours, 1, 7, 14 days after adminstration of DEHP or Cd. Absolute and relative testicular weight were lower in DEHP- or Cd-treated rats than control. DEHP or Cd produced morphological changes in testes, including apoptosis, degeneration, necrosis and massive loss of spermatogenic cells, resulting in testicular atrophy. The zinc concentration in testes was not different at day 1 after administration of DEHP, but was decreased at later times. Testicular zinc was lower at day 1, 2 in Cd-treated rats than control, but was higher at 7, 14 days after Cd administration. The levels of Fas and FasL mRNA were highly expressed in testes after administration of DEHP or Cd. These results suggest that the change of zinc level in testes might be a secondary effect of DEHP- or Cd-induced testicular toxicity, and Fas signal system might be play an important role in pocessing of apoptosis in testes by DEHP or Cd.