Identification of genital tract markers in the human seminal plasma using an integrative genomics approach

STUDY QUESTION Can protein biomarkers of the male genital tract be identified in human seminal plasma? SUMMARY ANSWER We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. WHAT IS KNOWN ALREADY The seminal plasma fulfills critical func...

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Bibliographic Details
Published in:Human reproduction (Oxford) 2013-01, Vol.28 (1), p.199-209
Main Authors: Rolland, A.D., Lavigne, R., Dauly, C., Calvel, P., Kervarrec, C., Freour, T., Evrard, B., Rioux-Leclercq, N., Auger, J., Pineau, C.
Format: Article
Language:English
Subjects:
Adult
biomarkers
Biomarkers - metabolism
Biopsy
Chromatography, High Pressure Liquid
Data processing
Epididymis
Fertility
Gene expression
Gene Expression Profiling
Genital Diseases, Male - metabolism
Genital tract
Genitalia, Male - metabolism
Genitalia, Male - secretion
genomics
Genomics - methods
Germ cells
Humans
Infertility
Infertility, Male - metabolism
Isoenzymes - chemistry
Isoenzymes - genetics
Isoenzymes - metabolism
L-Lactate Dehydrogenase - chemistry
L-Lactate Dehydrogenase - genetics
L-Lactate Dehydrogenase - metabolism
Life Sciences
Male
Mass spectroscopy
Organ Specificity
Patent applications
Peptide Fragments - chemistry
Peptide Fragments - genetics
Peptide Fragments - metabolism
Peptide Mapping
Phosphoglycerate Kinase - chemistry
Phosphoglycerate Kinase - genetics
Phosphoglycerate Kinase - metabolism
proteomics
Reproductive Biology
Reproductive system
Secretions
Semen
Semen - metabolism
Seminal Plasma Proteins - chemistry
Seminal Plasma Proteins - genetics
Seminal Plasma Proteins - metabolism
Sperm
Spermatozoa - metabolism
Spermatozoa - secretion
Tandem Mass Spectrometry
Testes
Transketolase - chemistry
Transketolase - genetics
Transketolase - metabolism
Trypsin
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Summary:STUDY QUESTION Can protein biomarkers of the male genital tract be identified in human seminal plasma? SUMMARY ANSWER We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. WHAT IS KNOWN ALREADY The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract. STUDY DESIGN, SIZE, DURATION This study combines proteomic analyses of normal seminal plasma together with transcriptomic gene expression profiling of human healthy tissues. MATERIALS, SETTING, METHODS Non-liquefied seminal plasma proteins from a healthy donor were prefractionated using two sequential Proteominer™ libraries. Eight subproteome fractions were collected, trypsin digested and subjected to three successive mass spectrometry analyses for peptide characterization. The list of identified proteins was compared with and merged with other available data sets of the human seminal plasma proteome. The expression of corresponding genes was then investigated using tissue transcriptome profiles to determine where, along the male reproductive tract, these proteins were produced. Finally, tissue specificity of a selected subset of biomarker candidates was validated on human tissues. MAIN RESULTS AND THE ROLE OF CHANCE We first performed a proteomic analysis of the human seminal plasma and identified 699 proteins. By comparing our protein list with other previous proteomic data sets, we found that 2545 unique proteins have been described so far in the human seminal plasma. We then profiled their expression at the gene level and identified 83 testis, 42 epididymis, 7 seminal vesicle and 17 prostate candidate protein markers. For a subset of testis-specific candidates, i.e. TKTL1, LDHC and PGK2, we further validated their germ cell expression and demonstrated that such markers could distinguish between semen from fertile and infertile men. LIMITATIONS, REASONS FOR CAUTION While some of the markers we identified are well-known tissue-specific products, further dedicated studies to validate the biomarker status of new candidates will be required. Additionally, whether or not the abundance of these proteins is indeed decreased in some specific pathological situations r
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/des360