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      An analysis of benign human prostate offers insights into the mechanism of apocrine secretion and the origin of prostasomes

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          Abstract

          The structure and function of normal human prostate is still not fully understood. Herein, we concentrate on the different cell types present in normal prostate, describing some previously unreported types and provide evidence that prostasomes are primarily produced by apocrine secretion. Patients ( n = 10) undergoing TURP were prospectively consented based on their having a low risk of harbouring CaP. Scanning electron microscopy and transmission electron microscopy was used to characterise cell types and modes of secretion. Zinc levels were determined using Inductively Coupled Plasma Mass Spectrometry. Although merocrine secretory cells were noted, the majority of secretory cells appear to be apocrine; for the first time, we clearly show high-resolution images of the stages of aposome secretion in human prostate. We also report a previously undescribed type of epithelial cell and the first ultrastructural image of wrapping cells in human prostate stroma. The zinc levels in the tissues examined were uniformly high and X-ray microanalysis detected zinc in merocrine cells but not in prostasomes. We conclude that a significant proportion of prostasomes, possibly the majority, are generated via apocrine secretion. This finding provides an explanation as to why so many large proteins, without a signal peptide sequence, are present in the prostatic fluid.

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          Most cited references23

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          Prostate cancer incidence in 43 populations worldwide: An analysis of time trends overall and by age group.

          Prostate cancer is a significant public health burden and a major cause of morbidity and mortality among men worldwide. Analyzing geographic patterns and temporal trends may help identify high-risk populations, suggest the degree of PSA testing, and provide clues to etiology. We used incidence data available from the International Agency for Research on Cancer (IARC) and certain cancer registries for 43 populations across five continents during a median period of 24 years. Trends in overall prostate cancer rates showed five distinct patterns ranging from generally monotonic increases to peaking of rates followed by declines, which coincide somewhat with changes in the prevalence of PSA testing. Trends in age-specific rates generally mirrored those in the overall rates, with several notable exceptions. For populations where overall rates increased rapidly and then peaked, exemplified in North America and Oceania, the highest incidence tended to be most pronounced and occurred during earlier calendar years among older men compared with younger ones. For populations with almost continual increases in overall rates, exemplified in Eastern Europe and Asia, peaks were evident among men aged ≥ 75 years in many instances. Rates for ages 45-54 years did not clearly stabilize or decline in the majority of studied populations. Global geographic variation remained substantial for both overall and age-specific incidence rates regardless of levels of PSA testing, with the lowest rates consistently in Asia. Explanations for the persistent geographic differences and the continuing increases of especially early-onset prostate cancer remain unclear.
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            Epididymosomes, prostasomes, and liposomes: their roles in mammalian male reproductive physiology.

            Mammalian spermatozoa are unique cells in many ways, and the acquisition of their main function, i.e. fertilization capacity, is a multistep process starting in the male gonad and ending near the female egg for the few cells reaching this point. Owing to the unique character of this cell, the molecular pathways necessary to achieve its maturation also show some specific characteristics. One of the most striking specificities of the spermatozoon is that its DNA is highly compacted after the replacement of histones by protamines, making the classical processes of transcription and translation impossible. The sperm cells are thus totally dependent on their extracellular environment for their protection against oxidative stress, for example, or for the molecular changes occurring during the transit of the epididymis; the first organ in which post-testicular maturation takes place. The molecular mechanisms underlying sperm maturation are still largely unknown, but it has been shown in the past three decades that extracellular vesicles secreted by the male reproductive tract are involved in this process. This review will examine the roles played by two types of naturally occurring extracellular vesicles, epididymosomes and prostasomes, secreted by the epididymis and the prostate respectively. We will also describe how the use of artificial vesicles, liposomes, contributed to the study of male reproductive physiology.
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              Prostasomes: extracellular vesicles from the prostate.

              The term 'prostasomes' is generally used to classify the extracellular vesicles (EVs) released into prostatic fluid by prostate epithelial cells. However, other epithelia within the male reproductive tract also release EVs that mix with 'true' prostasomes during semen emission or ejaculation. Prostasomes have been proposed to regulate the timing of sperm cell capacitation and induction of the acrosome reaction, as well as to stimulate sperm motility where all three are prerequisite processes for spermatozoa to attain fertilising capacity. Other proposed functions of prostasomes include interfering with the destruction of spermatozoa by immune cells within the female reproductive tract. On the other hand, it is unclear whether the distinct presumed functions are performed collectively by a single type of prostasome or by separate distinct sub-populations of EVs. Moreover, the exact molecular mechanisms through which prostasomes exert their functions have not been fully resolved. Besides their physiological functions, prostasomes produced by prostate tumour cells have been suggested to support prostate cancer spread development, and prostasomes in peripheral blood plasma may prove to be valuable biomarkers for prostate cancer.
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                Author and article information

                Contributors
                n.fullwood@lancaster.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                14 March 2019
                14 March 2019
                2019
                : 9
                : 4582
                Affiliations
                [1 ]ISNI 0000 0000 8190 6402, GRID grid.9835.7, Biomedical and Life Sciences, Faculty of Health and Medicine, Furness College, , Lancaster University, ; Lancaster, LA1 4YG UK
                [2 ]ISNI 0000 0000 8190 6402, GRID grid.9835.7, Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, ; Lancaster, LA1 4AP UK
                [3 ]ISNI 0000 0004 0391 9602, GRID grid.416204.5, Sharoe Green Lane North, Royal Preston Hospital, Fulwood, ; Preston, PR2 9HT UK
                [4 ]ISNI 0000 0001 2167 3843, GRID grid.7943.9, School of Pharmacy and Biomedical Sciences, , University of Central Lancashire, ; Preston, PR1 2HE UK
                Author information
                http://orcid.org/0000-0002-9405-8515
                http://orcid.org/0000-0001-8562-4944
                Article
                40820
                10.1038/s41598-019-40820-2
                6418221
                30872668
                283bca5a-4860-40fb-a156-d1fe6fd70f36
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 March 2018
                : 22 February 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000266, RCUK | Engineering and Physical Sciences Research Council (EPSRC);
                Award ID: EP/K023349/1
                Award ID: EP/K023349/1
                Award Recipient :
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