The last decade led to the discovery and characterization of several human β-defensins. Analysis of genomic information indicates that the number of β-defensin-like molecules encoded by the human genome may number in the tens. Growing interest in β-defensins steadily enhances our knowledge about various aspects of their gene location, expression patterns and the transcription factors involved in their regulation in vivo. The hallmark property of β-defensins, their antimicrobial activity, is clearly only the tip of the iceberg in the extensive network of inter-relations within the immune system in which these peptides function. Structural studies of β-defensins provide the molecular basis for a better understanding of their properties, functions and their potential for practical applications. In this review, we present some recent advances in the studies of human β-defensins, with an emphasis on possible correlations between their structural and functional properties.

Human β-defensins

Even tough differentiated spermatozoa are unable of transcriptional or translational activity; the sperm surface undergoes major modifications in macromolecules composition during the transit along the male reproductive tract. This is the result of sequential, well orchestrated interactions between the male reproductive tract secretions and the transiting male gamete. This is particularly true when spermatozoa transit along the epididymis. The epididymis is a long convoluted tubules in which the spermatozoa leaving the testis have to transit. The unraveled epididymal tubule can be as long as 80 m in stallion, and the transit time of spermatozoa is of 3–12 days depending on the species. The epididymis is usually divided in three segments: the caput (proximal part), the corpus, and cauda. While the cauda epididymides acts as a sperm reservoir, the caput and corpus are responsible for sperm maturation. This means that, under androgen control, the epididymal epithelium secretes proteins that will interact sequentially with sperm surface. Some of the sperm proteins acquired during maturation along the excurrent duct behave as integral membrane proteins. In fact, some epididymal originating proteins are glycosylphosphatidylinositol (GPI)-anchored to the sperm plasma membrane. Our laboratory has shown that some of these proteins are secreted in an apocrine manner by the epididymal epithelium and are associated to exosomes, called epididymosomes. Epididymosomes are rich in sphingomyelin and are characterized by a high cholesterol/phospholipids ratio. Many proteins are associated to epididymosomes, some of which are selectively transferred to spermatozoa during the epididymal transit. We have identified some of these exosomes associated proteins transferred to the maturing spermatozoa. These include two enzymes involved in the polyol pathway: an aldose reductase and a sorbitol dehydrogenase. A cytokine named MIF (macrophage migration inhibitory factor) is another protein associated to exosomes who is transferred to spermatozoa during the epididymal transit. We hypothesized that both the polyol pathway and MIF secreted in an apocrine fashion by the epididymal epithelium modulate sperm motility during the transit along the male reproductive tract. Finally, P25b, belonging to a family of sperm surface proteins (P26h/P34H) necessary for the binding to the surface of the egg, is also acquired through the interaction between epididymosomes and the male gamete. In vitro studies have defined the conditions of protein transfer when epididymal spermatozoa are co-incubated with epididymosomes. The transfer of selected proteins to specific membrane domains of spermatozoa is saturable, temperature and pH-dependent, being optimal at pH 6.5. The presence of zinc in the incubation medium, but not of calcium neither magnesium, significantly increases the efficiency of protein transfer. These results show that exosomes play a role in sperm epididymal maturation which is an essential event to produce male gametes with optimal fertilizing ability.

Role of exosomes in sperm maturation during the transit along the male reproductive tract.

During epididymal transit, spermatozoa acquire new proteins. Some of these newly acquired proteins behave as integral membrane proteins, including glycosylphosphatidylinositol (GPI)-anchored proteins. This suggests that the secreted epididymal proteins are transferred to spermatozoa by an unusual mechanism. Within the epididymal lumen, spermatozoa interact with small membranous vesicles named epididymosomes. Many proteins are associated with epididymosomes and the protein composition of these vesicles varies along the excurrent duct and differs from soluble intraluminal proteins. Some epididymosome-associated proteins have been identified and their functions in sperm maturation hypothesized. These include P25b, a zona pellucida binding protein, macrophage migration inhibitory factor, enzymes of the polyol pathway, HE5/CD52, type 5 glutathione peroxidase, and SPAM1 or PH-20. The electrophoretic patterns of proteins associated to epididymosomes are complex and some of these proteins are transferred to defined surface domains of epididymal spermatozoa. Epididymosomes collected from different epididymal segments interact differently with spermatozoa. This protein transfer from epididymosomes to spermatozoa is time-dependent, temperature-dependent and pH-dependent, and is more efficient in the presence of zinc. Some proteins are segregated to lipid raft domains of epididymosomes and are selectively transferred to raft domains of the sperm plasma membrane. Some evidence is presented showing that epididymosomes are secreted in an apocrine manner by the epididymal epithelial cells. In conclusion, epididymosomes are small membranous vesicles secreted in an apocrine manner in the intraluminal compartment of the epididymis and play a major role in the acquisition of new proteins by the maturing spermatozoa.

/pdf/epididymosomes-are-involved-in-the-acquisition-of-new-sperm-1boktwo7tg.pdf

Epididymosomes are involved in the acquisition of new sperm proteins during epididymal transit.

Maturation of spermatozoa, including the acquisition of motility and the ability to undergo capacitation, occurs during transit through the dynamic environment of the epididymis. The microenvironments created along the length of the epididymal tubule are essential to the molecular modifications of spermatozoa that result in fertile gametes. The secretory and resorptive processes of the epithelial cells that line this tubule generate these microenvironments. In the current study, 10 morphologically distinct segments of the mouse epididymis were identified by microdissection. We hypothesized that the changing environments of the epididymal lumen are established by differential gene expression among these segments. RNA isolated from each of the 10 segments was analyzed by microarray analysis. More than 17 000 genes are expressed in the mouse epididymis, compared with about 12 000 genes identified from whole epididymal samples. Screening a panel of normal mouse tissues identified both epididymal-selective and epididymal-specific transcripts. In addition, this study identified 2168 genes that are up-regulated or down-regulated by greater than 4-fold between at least two different segments. The expression patterns of these genes identify distinct patterns of segmental regulation. Using principal component analysis, we determined that the 10 segments form 6 different transcriptional units. These analyses elucidate the changes in gene expression along the length of the epididymis for 17 000 expressed transcripts and provide a powerful resource for the research community in future studies of the biological factors that mediate epididymal sperm maturation. epididymis, gene regulation, male reproductive tract, sperm maturation, sperm motility and transport

The Mouse Epididymal Transcriptome: Transcriptional Profiling of Segmental Gene Expression in the Epididymis

Background Spermatozoa acquire their fertilizing ability and forward motility properties during epididymal transit. Our knowledge of gamete physiology is based on studies conducted in laboratory and domestic species; our knowledge of these processes in humans is limited. Medical indications for assisted reproductive technologies (ART) have progressed to include male infertility. Surgical procedures allow collection of spermatozoa from all along the human excurrent ducts, and the former have been used with some success in reproductive medicine. This has raised questions over the role of the epididymis in human sperm physiology. Objective and rationale To reanalyze what we now know about epididymal physiology in humans and to assess the relevance of laboratory animal models for understanding human physiology and the pathophysiology of the epididymis. Search methods A systematic bibliographic search of PubMed for articles published in English before May 2015 was carried out using the search terms 'epididymis' and 'sperm maturation'. Literature on the consequences of vasectomy on the epididymis was also searched. Outcomes Whereas the proximal epididymis is almost exclusively occupied by efferent ducts, the sperm reservoir capacity is poorly developed in humans. At the molecular level, the human transcriptome and proteome show some segment specificity; conflicting results persist with regard to secretome variation along the tubule. The number of genes regulated along the excurrent ducts in men is lower when compared to rodent species, but remains significant. It is challenging to reconcile biochemical and physiological studies with clinical data obtained from men undergoing reanastomosis of the vas deferens at different points along the excurrent duct. We propose that vasectomy/vasovasostomy is a model to understand the consequences of obstruction on epididymis function in humans. Wider implications Despite the scarcity of biological material available, the interspecies variability of the male reproductive tract urges us to use modern molecular and cellular biology tools to better understand human epididymis physiology in order to apply ART in a more responsible manner.

/pdf/the-human-epididymis-its-function-in-sperm-maturation-3139bblk3f.pdf

The human epididymis: its function in sperm maturation

The epididymis is a tubular organ exhibiting vectorial functions of sperm concentration, maturation, transport, and storage. The molecular basis for these functions is poorly understood. However, it has become increasingly clear that regional differences along the length of the duct play a role in epididymal physiology and that region-specific gene expression is involved in the formation of these differences. Although not an overtly segmented organ, the epididymis consists of a series of highly coiled “zones,”separated by connective tissue septulae and distinct by cell morphology and their pattern of gene expression. Thus, it constitutes an interesting mammalian model to study how pattern formation is achieved by differential gene activity. A large number of epididymis-expressed genes have been cloned and analyzed at the molecular level, most of them have been characterized by a distinct temporal and spatial expression pattern within the organ. Only recently have theories been developed about how and when during ontogenesis this pattern formation takes place and what its significance might be. This review summarizes the current knowledge on regionalized gene expression in the epididymis and presents hypotheses concerning its ontogenetic origin and regulation in the adult.

Gene Expression in the Epididymis

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Kirchhoff C

Author Tools

Chat about Author

Papers

Gene Expression in the Epididymis