Increased apoptosis in a variety of tissues of zinc-deficient rats

Zinc deficient rats were prepared to investigate histopathological changes in thymus, testis, skin, esophagus, kidney and liver and the relationship b etween these changes and apoptosis. Seven-week-old male SD rats were given a Zn deficient diet (0% Zn diet) or a standard diet (0.02% Zn diet). The ab ove-mentioned organs were excised 1, 2, 3, 4, 5, 10, 13, and 34 weeks after initiating diet administration. Then, these organs were examined morpholog ically, and apoptotic changes were analyzed by either the TdT- mediated dUT P - biotin nick end labeling (TUNEL) or electrophoresis. Significant morpho logical changes were seen only in rats on the 0% Zn diet. After 4 weeks, at rophy of the thymus was seen. After 5 weeks, oligospemia was observed, and after 10 weeks, testicular atrophy accompanied by the loss of sperm cells a nd spermatocytes was confirmed. In addition, after 10 weeks, thickening of epithelia was seen in the skin and esophagus of rats on the 0% diet. During the observation period, no marked morphological changes were observed in t he liver or kidney. In the thymus and testis of rats do the 0% Zn diet, pri or to detecting any morphological changes, increases in apoptosis were conf irmed at 1 and 3 weeks after initiating diet administration, respectively. In the kidney and liver, TUNEL positive cells appeared after 13 and 34 week s, respectively. These observations suggest that the functional and morphol ogical changes in the thymus and testis of rats on the 0% Zn diet are cause d by increased apoptosis, and that even when the supply of Zn is terminated for only a short period of time, immunocytes and germ cells can not surviv e or regenerate sufficiently. Again, the fact that even in the liver and ki dney, apoptosis was observed when administration of the 0% Zn diet was prol onged suggests that the appearance of apoptosis is dependent on the amount of Zn in tissues. In addition, the fact that increases in apoptosis were co nfirmed in the skin of rats on the 0% Zn diet, but not in the esophagus of these rats suggests that apoptosis does not directly cause thickening of st ratified squamous epithelium in Zn deficient rats. (C) 2001 Elsevier Scienc e Inc. All rights reserved.