Background
Year | Technique used | Outcome | Reference |
---|---|---|---|
1888 | Acetic acid precipitation | Detection of propeptone | [16] |
1942 | Electrophoresis (Tiselius apparatus) | First electrophoretic separation that identified 4 protein fractions | [18] |
1942 | Electrophoresis (Tiselius apparatus) | Electrophoretically separated 4 protein fractions correspond to albumin, α-, β- and γ-globulins | [17] |
1978 | 2DE | Separated 40 peptides and identified p30 as a marker for semen in forensic samples (vaginal swabs). Established the idea that semen proteins can act as biomarkers | [19] |
1981 | 2DE | Detected > 200 peptides and reported the absence of many glycoproteins in vasectomized men | [20] |
2003 | 2DE-MALDI-TOF-MS | Detected impaired spermatogenesis-associated markers by narrow immobilized pH gradients in azoospermic men | [21] |
2007 | 2DE-LC-MS/MS | Reported candidate marker proteins for non-obstructive and obstructive azoospermia | [26] |
2009 | 1DE-LC-MS/MS | Proposed that downregulation of DJ-1 is responsible for oxidative stress and thereby affects the quality of the semen in asthenozoospermia | [27] |
2011 | N-linked glycosylated peptide enrichment, combined with LC-MS/MS | N-glycosylated prostate-specific antigen is known to be an efficient biomarker that can distinguish benign prostate hyperplasia from prostate cancer | [30] |
2012 | 2DE-LC-MS/MS | Identified 59 proteins in seminal plasma as candidate biomarkers of prostatitis | [28] |
2013 | LC-MS/MS | Testis-specific TKTL1, LDHC and PGK2 could distinguish semen from fertile and infertile men | [23] |
2013 | 1DE-LC-MS/MS | Identified proteins that are over- or underexpressed in the seminal plasma of teratozoospermic, oligozoospermic and oligoteratozoospermic men | [29] |
2014 | LC-MS/MS followed by MS-based multiplex SRM assay | ECM1 and TEX101 levels can distinguish OA from NOA and circumvent testicular biopsies for prediction of outcome of sperm retrieval in azoospermic patients | [6] |
2015 | 1DE-LC-MS/MS | MME and FAM3D along with ROS levels in the seminal plasma may serve as good markers for diagnosis of male infertility | [24] |
2016 | LC-MS/MS | Cab45/SDF4, protein lefty-1, DNase I, PAP2-alpha, IBP-7, HDC, and CRISP-3 are proposed as putative biomarkers in adolescents with varicocele | [25] |
Review criteria
Composition of seminal plasma
History and evolution of the study of seminal plasma proteome
Proteomic signatures of seminal plasma in evaluation of male infertility
Condition | Identified protein markers | Reference |
---|---|---|
Poor semen parameters/azoospermia | PGDS | |
Obstructive and non-obstructive azoospermia | TEX101, ECM1 | [33] |
Azoospermia vs normo-, astheno- and oligozoospermia | Fibronectin, PAP, PIP, B2M, PSMA3, LGALS3BP, CNDP2 | [13] |
Infertility | Semenogelin I/II, olfactory receptor 5R1, Lactoferin, hCAP18, Spindling 1, Clusterin | [3] |
Abnormal semen parameters, ROS and asthenozoospermia | DJ-1 | |
ROS and prostate cancer | LGALS3BP | [37] |
Different levels of ROS and infertility | MME, FAM3D | [24] |
Fertile vs infertile | TKTL1, LDHC, PGK2 | [23] |
Seminal exosomal proteins and their role in sperm function
Protective role of seminal plasma molecules in fertilization
Proteins involved | Site of Action | Mechanism of action | Reference |
---|---|---|---|
FOXP3 | Uterine regulatory T cells | Immunosuppression and improved tolerance towards paternal antigens | |
GM-CSF | Embryo | Blastocyst stage development | [72] |
IL-6 | Embryo | Protection from apoptosis by secreting anti-apoptotic micro RNAs | [72] |
LIF | Inner cell mass | Blastocyst development | [72] |
IGF-1 | Germ cells | Maturation of spermatozoa | |
α2-macroglobulin | Germ cells | Progressive motility | |
Enkephalin | Sperm cells | Sperm motility | |
VEGF, MMPs | Endometrium | Embryo implantation | |
TGF-β, PGE | Female reproductive epithelial tissues | Inflammatory signaling response | |
GM-CSF, IL-1A, IL-6, IL-8, MCP-1 (CCL2), MIP3A (CCL20) | Female epithelial layers and deeper stromal tissues | Immediate and rapid influx of inflammation to cause fertilization |