抄録
Phthalate esters have been used as plasticizers of synthetic polymers. Recent studies revealed that they induce atrophy of the testis, although its pathogenesis remains unknown. Testicular atrophy with aspermatogenesis was induced by feeding with 2% DEHP-containing diet. The biochemical and immunohistochemical analysis revealed that DEHP increased the reactive oxygen species generation, with concomitant decrease of glutathione and ascorbic acid, and selectively induced apoptosis of spermatocytes, thereby causing atrophy. Oxidative stress was selectively induced in germ cells, but not in Sertoli cells, treated with mono(2-ethylhexyl)phthalate (MEHP), a hydrolysed metabolite of DEHP. Furthermore, MEHP selectively induced the release of cytochrome c from mitochondria of the testis. These results indicate that oxidative stress elicited by MEHP principally injured mitochondrial function, and induced apoptosis of spermatocytes and atrophy of the testis. Using the 2% DEHP-dose, the effect of simultaneous administration of vitamins C and E was examined. The vitamin supplementation significantly prevented the testicular injury. Results suggest that antioxidant vitamins can protect the testes from DEHP-toxicity. Some of rare sugars (i.e. D-psicose and D-allose) are also effective in prevention of the testicular injury. Microarray analysis has been applied to elucidate the genes involved in the DEHP-toxicity and the protection mechanism. [J Physiol Sci. 2006;56 Suppl:S119]
