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Adaptive evolution of proteins secreted during sperm maturation: an analysis of the mouse epididymal transcriptome.

ABSTRACT: A common pattern observed in molecular evolution is that reproductive genes tend to evolve rapidly. However, most previous studies documenting this rapid evolution are based on genes expressed in just a few male reproductive organs. In mammals, sperm become motile and capable of fertilization only after leaving the testis, during their transit through the epididymis. Thus, genes expressed in the epididymis are expected to play important roles in male fertility. Here, we performed evolutionary genetic analyses on the epididymal transcriptome of mice. Overall, epididymis-expressed genes showed evidence of strong evolutionary constraint, a finding that contrasts with most previous analyses of genes expressed in other male reproductive organs. However, a subset of epididymis-specialized, secreted genes showed several signatures of adaptive evolution, including an increased rate of nonsynonymous evolution. Furthermore, this subset of genes was overrepresented on the X chromosome. Immunity and protein modification functions were significantly overrepresented among epididymis-specialized, secreted genes. These analyses identified a group of genes likely to be important in male reproductive success.

SUBMITTER: Dean MD

PROVIDER: S-EPMC2915769 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Adaptive evolution of proteins secreted during sperm maturation: an analysis of the mouse epididymal transcriptome.

Dean Matthew D MD Good Jeffrey M JM Nachman Michael W MW

Molecular biology and evolution 20071201 2

A common pattern observed in molecular evolution is that reproductive genes tend to evolve rapidly. However, most previous studies documenting this rapid evolution are based on genes expressed in just a few male reproductive organs. In mammals, sperm become motile and capable of fertilization only after leaving the testis, during their transit through the epididymis. Thus, genes expressed in the epididymis are expected to play important roles in male fertility. Here, we performed evolutionary ge ...[more]

PMID: 18056076

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Project description:BackgroundPaternal lifestyle choices and male exposure history have a critical influence on the health and fitness of the next generation. Accordingly, defining the processes of germline programming is essential to resolving how the epigenetic memory of paternal experiences transmits to their offspring. Established dogma holds that all facets of chromatin organization and histone posttranslational modification are complete before sperm exits the testes. However, recent clinical and animal studies suggest that patterns of DNA methylation change during epididymal maturation. In this study, we used complementary proteomic and deep-sequencing approaches to test the hypothesis that sperm posttranslational histone modifications change during epididymal transit.ResultsUsing proteomic analysis to contrast immature spermatozoa and mature sperm isolated from the mouse epididymis, we find progressive changes in multiple histone posttranslational modifications, including H3K4me1, H3K27ac, H3K79me2, H3K64ac, H3K122ac, H4K16ac, H3K9me2, and H4K20me3. Interestingly, some of these changes only occurred on histone variant H3.3, and most involve chromatin modifications associated with gene enhancer activity. In contrast, the bivalent chromatin modifications, H3K4me3, and H3K27me3 remained constant. Using chromatin immunoprecipitation coupled with deep sequencing, we find that changes in histone h3, lysine 27 acetylation (H3K27ac) involve sharpening broad diffuse regions into narrow peaks centered on the promoter regions of genes driving embryonic development. Significantly, many of these regions overlap with broad domains of H3K4me3 in oocytes and ATAC-seq signatures of open chromatin identified in MII oocytes and sperm. In contrast, histone h3, lysine 9 dimethylation (H3K9me2) becomes enriched within the promoters of genes driving meiosis and in the distal enhancer regions of tissue-specific genes sequestered at the nuclear lamina. Maturing sperm contain the histone deacetylase enzymes HDAC1 and HDAC3, suggesting the NuRD complex may drive some of these changes. Finally, using Western blotting, we detected changes in chromatin modifications between caput and caudal sperm isolated from rams (Ovis aries), inferring changes in histone modifications are a shared feature of mammalian epididymal maturation.ConclusionsThese data extend our understanding of germline programming and reveal that, in addition to trafficking noncoding RNAs, changes in histone posttranslational modifications are a core feature of epididymal maturation.

Project description:PurposeDuring epididymal sperm maturation, spermatozoa acquire progressive motility through dynamic protein modifications. However, the relationship between sequential protein modifications during epididymal sperm maturation and sperm motility and fertility has not yet been investigated. This study investigated whether sequential changes in fertility-related protein expression including that of enolase 1 (ENO1), ubiquinol-cytochrome c reductase core protein 1 and 2 (UQCRC1 and UQCRC2), and voltage-dependent anion channel 2 (VDAC2) in spermatozoa during epididymal maturation are related to bovine sperm motility. Moreover, we found that mitochondrial metabolism is closely related to fertility-related proteins. Therefore, we investigated how the sequential modification of mitochondrial proteins during epididymal maturation regulates sperm motility.Materials and methodsTo determine the differential protein expression in caput and cauda epididymal spermatozoa from low and high motility bulls, western blot analysis was performed. Moreover, signaling pathways were identified to understand the mechanisms of regulation of sperm motility through the differential protein expression associated with fertility-related proteins.ResultsWe found that ENO1 was substantially higher in the caput spermatozoa from low motility bulls than the caput and cauda spermatozoa from high motility bulls. However, ENO1 expression in low motility bull spermatozoa was downregulated to a level comparable to that in the high motility bull spermatozoa during epididymal maturation. Moreover, there was a lack of modification of mitochondrial proteins, including glutathione peroxidase 4 and NADH:Ubiquinone Oxidoreductase Core Subunit S8, in low motility bull spermatozoa during epididymal maturation, whereas active changes were detected in high motility bull spermatozoa.ConclusionsIrregular modifications of mitochondrial proteins during epididymal sperm maturation may increase excessive ROS production and premature activation of spermatozoa during epididymal maturation. Consequently, spermatozoa may lose their motility by the earlier consumption of their energy source and may be damaged by ROS during epididymal maturation, resulting in a decline in sperm motility and bull fertility.

Dataset Information

Adaptive evolution of proteins secreted during sperm maturation: an analysis of the mouse epididymal transcriptome.

Publications

Adaptive evolution of proteins secreted during sperm maturation: an analysis of the mouse epididymal transcriptome.

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