The seminal vesicle-specific proteome

The seminal vesicle transcriptome

Transcriptome analysis of the seminal vesicle can be visualized with regard to specificity and distribution of transcribed mRNA molecules (Figure 1). Specificity illustrates the number of genes with elevated or non-elevated expression in the seminal vesicle compared to other tissues. Elevated expression includes three subcategory types of elevated expression:

• Tissue enriched: At least four-fold higher mRNA level in seminal vesicle compared to any other tissues.
• Group enriched: At least four-fold higher average mRNA level in a group of 2-5 tissues compared to any other tissue.
• Tissue enhanced: At least four-fold higher mRNA level in seminal vesicle compared to the average level in all other tissues.

Distribution, on the other hand, visualizes how many genes that have, or do not have, detectable levels (NX≥1) of transcribed mRNA molecules in the seminal vesicle compared to other tissues. As evident in Table 1, all genes elevated in seminal vesicle are categorized as:

• Detected in single: Detected in a single tissue
• Detected in some: Detected in more than one but less than one third of tissues
• Detected in many: Detected in at least a third but not all tissues
• Detected in all: Detected in all tissues

Figure 1. (A) The distribution of all genes across the five categories based on transcript specificity in seminal vesicle as well as in all other tissues. (B) The distribution of all genes across the six categories, based on transcript detection (NX≥1) in seminal vesicle as well as in all other tissues.

As shown in Figure 1, 180 genes show some level of elevated expression in the seminal vesicle compared to other tissues. The three categories of genes with elevated expression in seminal vesicle compared to other organs are shown in Table 1. In Table 2, the 2 enriched genes are defined.

Table 1. Number of genes in the subdivided categories of elevated expression in seminal vesicle.

Table 2. The 2 genes with enriched expression in seminal vesicle. "Tissue distribution" describes the transcript detection (NX≥1) in seminal vesicle as well as in all other tissues. "mRNA (tissue)" shows the transcript level in seminal vesicle as NX values. "Tissue specificity score (TS)" corresponds to the fold-change between the expression level in seminal vesicle and the tissue with second highest expression level.

Protein expression of genes elevated in seminal vesicle

In-depth analysis of the elevated genes in seminal vesicle using antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in different functional compartments including proteins related to insemination and sperm motility as well as protection.

Proteins related to sperm motility and protection in seminal vesicle

The proteins that are encoded by the genes SEMG1 and SEMG2 are the predominant proteins in semen. These secreted proteins are involved in the formation of a gel matrix that encases ejaculated spermatozoa. The preproproteins of SEMG1 and SEMG2 are proteolytically processed by the prostate-specific antigen (PSA) protease to generate multiple peptide products that exhibit distinct functions. One of these peptides is an antimicrobial peptide with antibacterial activity. This proteolysis process also breaks down the gel matrix and allows the spermatozoa to move more freely.

SEMG1
SEMG2

Tight junctions hold cells together and function as a protective barrier preventing unwanted molecules and ions to pass the plasma membrane and the adjacent cells. The protein expressed by CLDN2 belongs to the claudin protein family whose members have been identified as major integral membrane proteins localized exclusively at tight junctions. Claudins are expressed in an organ-specific manner and regulate tissue-specific physiologic properties of tight junctions. The ZNF185 gene encodes a zinc-finger protein that binds to nucleic acids and plays important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This gene encodes a LIM-domain zinc finger protein. The LIM domain is composed of two contiguous zinc finger domains, separated by a two-amino acid residue hydrophobic linker. The LIM domain mediates protein-protein interactions.

CLDN2
ZNF185

Another example of an enhanced gene is the MUC6 gene that encodes a member of the mucin protein family. Mucins are high molecular weight glycoproteins produced by many epithelial tissues, including the stomach and duodenum. MUC6 protein expression has been found in the gastrointestinal system as well as in the seminal vesicles and ductus deferens. The protein encoded by this gene is secreted and forms an insoluble mucous barrier that protects the lumen in several tissues, including the seminal vesicles.

MUC6 - seminal vesicle
MUC6 - stomach

Gene expression shared between the seminal vesicle and other tissues

There are 36 group enriched genes expressed in seminal vesicle. Group enriched genes are defined as genes showing a 4-fold higher average level of mRNA expression in a group of 2-5 tissues, including seminal vesicle, compared to all other tissues.

In order to illustrate the relation of seminal vesicle tissue to other tissue types, a network plot was generated, displaying the number of genes with shared expression between different tissue types.

Figure 2. An interactive network plot of the seminal vesicle enriched and group enriched genes connected to their respective enriched tissues (grey circles). Red nodes represent the number of seminal vesicle enriched genes and orange nodes represent the number of genes that are group enriched. The sizes of the red and orange nodes are related to the number of genes displayed within the node. Each node is clickable and results in a list of all enriched genes connected to the highlighted edges. The network is limited to group enriched genes in combinations of up to 3 tissues, but the resulting lists show the complete set of group enriched genes in the particular tissue.

The KIAA1210 gene is group enriched in seminal vesicle, epididymis and testis. The protein expression in seminal vesicle and epididymis, both excretory male glands, is restricted to the fibromuscular tissues surrounding the glandular epithelia, while the expression in testis is mainly detected in Sertoli cells.

KIAA1210 - seminal vesicle
KIAA1210 - epididymis
KIAA1210 - testis

Seminal vesicle function

Testosterone is the main regulator of morphology and secretory function in the seminal vesicles and the thick layer of smooth muscle surrounding the glands force the sperm out through the urethra during ejaculation. Spermatozoa require fructose as their largest nutrient which is provided by the secreting cells in the seminal vesicles. The secretory cells provide 70-80% of the total ejaculate content. Proteins, amino acids, citric acid and ascorbic acids among other important nutrients are released to facilitate sperm survival and transportation. Large amounts of prostaglandins are produced in the glands of the seminal vesicle. Prostaglandins stimulate inflammatory reactions among several other processes in our body.

Seminal vesicle histology

The seminal vesicles are paired, highly coiled, tubular structures located above the prostate and behind the urinary bladder. The seminal vesicles merge with vas deferens before debouching into the intra-prostatic urethra. The pseudostratified columnar epithelium in seminal vesicles is surrounded by thick fibromuscular tissue. The vesicle epithelium is composed of columnar and basal epithelial cells. The columnar epithelium typically contains large amounts of lipofuscin pigment. An unusual feature of normal epithelial cells is the feature of cellular atypia. However, atypical cells are often encountered in the seminal vesicle epithelium, where epithelial cells with large atypical nuclei often are present.

The histology of human seminal vesicle including detailed images and information about the different cell types can be viewed in the Protein Atlas Histology Dictionary.

Background

Here, the protein-coding genes expressed in seminal vesicle are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in seminal vesicle.

Transcript profiling was based on a combination of three transcriptomics datasets (HPA, GTEx and FANTOM5), corresponding to a total of 9332 samples from 113 different human normal tissue types. The final consensus normalized expression (NX) value for each tissue type was used for classification of all genes according to the tissue specific expression into two different categories, based on specificity or distribution.

Relevant links and publications

Uhlén M et al., Tissue-based map of the human proteome. Science (2015)
PubMed: 25613900 DOI: 10.1126/science.1260419

Yu NY et al., Complementing tissue characterization by integrating transcriptome profiling from the Human Protein Atlas and from the FANTOM5 consortium. Nucleic Acids Res. (2015)
PubMed: 26117540 DOI: 10.1093/nar/gkv608

Fagerberg L et al., Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. (2014)
PubMed: 24309898 DOI: 10.1074/mcp.M113.035600

Histology dictionary - the seminal vesicle