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BOR - Papers in Press, published online ahead of print June 2, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.028886
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Submitted February 24, 2004
Returned for revision March 15, 2004
Accepted May 7, 2004

Male Reproductive Tract


The Effects of Long Term Vitamin E Treatment on Gene Expression and Oxidative Stress Damage in the Aging Brown Norway Rat Epididymis

Kathryn M. Jervis and Bernard Robaire *

* To whom correspondence should be addressed. E-mail: brobaire{at}pharma.mcgill.ca.

Abstract
The male reproductive tract of the Brown Norway rat is profoundly affected by aging. In the epididymis, the site of sperm maturation and storage, aging results in histological and biochemical changes that are suggestive of oxidative stress. Vitamin E is a potent lipid soluble antioxidant that ameliorates the oxidative stress load associated with some chronic disease conditions. To determine the effects of long term (18 month) vitamin E deficiency and supplementation on aging in the epididymis, we assessed gene expression changes using cDNA microarrays and lipid peroxidation using immunohistochemical detection of 4-hydroxynonenal (4-HNE) in 24 month old rats. Plasma vitamin E levels were significantly lower in vitamin E deficient animals, and higher in vitamin E supplemented animals, compared to age matched controls. Vitamin E deficiency resulted in increased expression of oxidative stress related transcripts along the epididymis. This effect was most marked in the corpus epididymidis where expression of glutathione S-transferases pi, 8 and mu as well as superoxide dismutase increased by over 50%. The effect of vitamin E supplementation on the expression of oxidative stress related transcripts was primarily decreased expression; however, the magnitude of the gene expression changes was smaller than that observed for vitamin E deficiency. 4-HNE immunostaining was present throughout the epididymis in control animals. Vitamin E deficiency both increased the intensity and altered the distribution of 4-HNE staining, while vitamin E supplementation had no observable effect. In summary we found that long-term vitamin E treatment alters the expression of oxidative stress related transcripts. Moreover long term vitamin E deficiency exacerbates the effects of age on the accumulation of oxidative stress damage in the epididymis.

Key words: Male Reproductive Tract • Aging • Epididymis • Stress


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