Oxidatively damaged proteins in the early stage of testicular toxicities in male rats by orally administered with a synthetic oestrogen, diethylstilbestrol

The molecular mechanism of severe adverse effects of the endocrine disruptor diethylstilbestrol (DES) on reproductive organs is not currently understood. The effects of DES on testicular proteins were studied in adult male rats orally treated with 0.35 and 3.5 mg DES/kg every two days for two weeks before the manifestation of morphological toxicities. Two up-regulated proteins (glutamine synthetase and chaperonin containing TCP1), two down-regulated proteins (thioredoxin-like 1 and testis-specific autoantigen) and two proteins with altered isoelectric points (protein disulfide isomerase [PDI a3] and enolase 1) were identified in DES groups. Carbonylation of PDI a3 was detected. A significant decrease in PDI activity and significant increases in caspase-12 and calpain activities were also found in the group. It is suggested that testicular toxicity by DES was initiated by the down-regulation of thioredoxin-like-1 leading to the cellular redox inbalances, and the resultant oxidative modification of several important proteins involved in protein foldings. (C) 2010 Elsevier Inc. All rights reserved.