Abstract
Male reproductive aging, or andropause, is associated with gradual age-related changes in testicular properties, sperm production, and erectile function. The testis, which is the primary male reproductive organ, produces sperm and androgens. To understand the transcriptional changes underlying male reproductive aging, we performed transcriptome analysis of aging testes in mice. A total of 31,386 mRNAs and 9387 long non-coding RNAs (lncRNAs) were identified in the mouse testes of diverse age groups (3, 6, 12, and 18 months old) by total RNA sequencing. Of them, 1571 mRNAs and 715 lncRNAs exhibited changes in their levels during testicular aging. Most of these aging-related transcripts exhibited slight and continuous expression changes during aging, whereas some (9.6%) showed larger expression changes. The aging-related transcripts could be classified into diverse expression patterns, in which the transcripts changed mainly at 3–6 months or at 12–18 months. Our subsequent in silico analysis provided insight into the potential features of testicular aging-related mRNAs and lncRNAs. We identified testis-specific aging-related transcripts (121 mRNAs and 25 lncRNAs) by comparison with a known testis-specific transcript profile, and then predicted the potential reproduction-related functions of the mRNAs. By selecting transcripts that are altered only between 3 and 18 months, we identified 46 mRNAs and 34 lncRNAs that are stringently related to the terminal stage of male reproductive aging. Some of these mRNAs were related to hormonal regulation. Finally, our in silico analysis of the 34 aging-related lncRNAs revealed that they co-localized with 19 testis-expressed protein-coding genes, 13 of which are considered to show testis-specific or -predominant expression. These nearby genes could be potential targets of cis-regulation by the aging-related lncRNAs. Collectively, our results identify a number of testicular aging-related mRNAs and lncRNAs in mice and provide a basis for the future investigation of these transcripts in the context of aging-associated testicular dysfunction.
Highlights
Male reproductive aging, or andropause, refers to age-related changes in male reproductive integrity, including sperm production and erectile function [1]
To investigate the potential effect of aging on the transcriptome related to testis-specific features, such as spermatogenesis, we identified aging-related mRNAs and long non-coding RNAs (lncRNAs) that are thought to be exclusively expressed in testes
We comprehensively investigated transcriptional changes associated with biological aging in adult mouse testis
Summary
Andropause, refers to age-related changes in male reproductive integrity, including sperm production and erectile function [1]. Unlike menopause resulting from female reproductive aging, which is relatively abrupt, male reproductive aging is accompanied by slow changes in function [1,2]. These gradual dysfunctional changes occur mostly in the testis, which is the main male reproductive organ and is responsible for producing sperm and hormones [1,2,3]. Spermatogenesis is the unique, complex, and tightly regulated process of male germ cell development [5]. LncRNAs could function as novel regulatory molecules which interact with DNA, RNA, and proteins They are implicated in various biological process, including differentiation and development. We recently reported that the testicular germ cell-specific lncRNA, Teshl, functions to regulate the expression of sex chromosome genes and maintain the quality of
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