Changes in gene expression during aging in the Brown Norway rat epididymis.

Aging of the Brown Norway rat is associated with a decline in reproductive function. With advancing age, serum testosterone and sperm production decrease and sperm morphology is altered. In the epididymis, the site of sperm maturation and storage, dramatic histological and biochemical changes occur with age; these changes occur in a region-specific manner. In order to provide insight into the process of aging in the epididymis, we employed cDNA microarrays to analyze changes in gene expression with age in the initial segment, caput, corpus and cauda epididymidis. The overwhelming effect was a decrease in the relative intensity of gene expression during aging. In the initial segment, corpus and cauda epididymidis, more genes had decreased relative intensity with age than did not change. Interestingly, the magnitude of the decreases in relative intensity was considerably larger in the corpus and cauda epididymidis, where expression of 83% (211 of 254) and 62% (157 of 254), respectively, of the genes decreased by greater than 50% with age. This is in contrast to the initial segment, in which only 31% of genes (78 of 254) had relative intensities that decreased by at least 50%, and the caput epididymidis, the only segment where the largest proportion of genes did not change with age (less than 33% change between young and old). No genes had increased relative intensity with age throughout the tissue, however the expression of four transcripts was increased in a segment-specific manner. The expression of oxidative stress related genes, heat shock proteins and components of intracellular degradation pathways were examined in particular detail. We found that the relative intensity of some gene families decreased with age in a segment-specific manner; these decreases correlated well with the histological changes that occur in the aging epididymis.