Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary

Abstract

Background: The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on ad libitum (AL) feeding with a group on lifespan-extending 40% calorie restriction (CR).

Results: We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months), whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis.

Conclusion: Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary.

Figure 1

Global patterns of gene expression in ovary and testis in mice of age from 1 to 24 months, and on an AL or a CR diet. (A) Experimental design for females; (B) two-dimensional heatmap of expression of 3000 most significant genes in ovary; (C) three-dimensional heatmap of expression of the same genes in ovary; (D) experimental design for males; (E) two-dimensional heatmap of expression of 3000 most significant genes in testis (819 genes overlapped with ovary); (F) three-dimensional heatmap of expression of the same genes in testis.

Figure 2

Functional groups of genes affected by age. (A) Ovary and (B) testis. Pie charts show the proportion of genes that were over-expressed either in ovary or testis by at least two-fold. Functional categories of genes were assembled from GO annotations and from PubMed.

Figure 3

Functional groups of genes affected by diet (AL versus CR). (A) Ovary and (B) testis. Pie charts show the proportion of genes that were over-expressed either in ovary or testis by at least two-fold. Functional categories of genes were assembled from GO annotations and from PubMed.

Figure 4

Age-specific effect of diet (AL versus CR). (A), (B) Numbers of age-dependent genes which were also affected by diet at specific age from 6 to 24 months in ovary and testis, respectively. (C), (D) Proportion of genes that were over-expressed either in ovary or testis, respectively, by at least two-fold among genes that were increased or decreased by CR at specific age from 6 to 24 months.