Review Article

Power of Proteomics in Linking Oxidative Stress and Female Infertility

Table 1

Proteins identified in relation to endometriosis.

Protein assessed/technique of assessmentFunction and site of expressionSourceAssociation with endometriosisPopulation sizeReference

Fibrinogen B peptide/SELDI-TOF-MSHelps in blood coagulation, regulation of cell adhesion, and spreading.PlasmaDecreased in endometriosis due to overconsumption and the consequence is adhesion of endometrial fragments.254 samples from women who underwent laparoscopy with or without pelvic pain. 89 women without endometriosis and 165 with endometriosis[47]

Afamin/ELISA or 2D-gel electrophoresis Vitamin E binding protein.Peritoneal fluidIncreased causing a decrease in antioxidant activity242 reproductive age women. [65]
ā€‰24 samples of peritoneal fluid from symptomatic women [8]
[8, 69]

Hemopexin/2Dgel electrophoresisHeme binding proteinPeritoneal fluid Decreased leading to oxidative stress24 samples of peritoneal fluid from symptomatic women [8]

Inter-alpha inhibitor H4 (ITIH4)/2Dgel electrophoresis Not clear but involved in acute phase inflammationPeritoneal fluid Increased in peritoneal endometriosis.24 samples of peritoneal fluid from symptomatic women [8]

Apolipoprotein A4/2Dgel electrophoresisBind lipids to form lipoproteins. Peritoneal fluidDecreased in ovarian endometriosis24 samples of peritoneal fluid from symptomatic women [8]

Haptoglobin/2Dgel electrophoresisHemoglobin binding proteinPeritoneal fluidIncreased. Removes iron and prevents oxidative stress24 samples of peritoneal fluid from symptomatic women [8]

Vitronectin/2Dgel electrophoresisInvolved in cell migration, adhesion, and invasion.Peritoneal fluid Increased24 samples of peritoneal fluid from symptomatic women [8]

SERPINA/2Dgel electrophoresisAssociated with inflammatory outcomesPeritoneal fluid Increased and might be a good biomarker24 samples of peritoneal fluid from symptomatic women [8]

Superoxide dismutase (SOD)/mass spectrometry, high performance liquid chromatography, and ELISABreakdown of superoxide radical into hydrogen peroxide and oxygenFollicular fluidDecreased leading to oxidative stress91 infertile women who were going to undergo IVF, 23 with endometriosis identified by laparoscopy or ultrasound and 68 infertile due to different reasons (not endometriosis)[31]

Thioredoxin binding protein 2 (TBP)/ELISA Binds thioredoxin (TRX) which is an antioxidantCells from endometriosis tissue It was noted that there is an increase in the TRX/TBP in endometriosis patients 66 women 35 with confirmed endometriosis and 31 patients without endometriosis as a control[70]

Interleukins (IL-6, IL-10, and IL-1B)Function in the immune system of different cells.Serum and follicular fluidIncrease in follicular fluid showing immune involvement with the disease38 patients, 20 with endometriosis, and 18 controls[71]

Vascular endothelial growth factor/ELISAIncrease in vascular permeability Peritoneal fluid Increases in patients with endometriosis 43 patients in reproductive age who were undergoing diagnostic laparoscopy for dysmenorrhea or elective laparoscopy for infertility, 19 controls without endometriosis, and 24 patients with endometriosis[72]

G antigen family B/Mass spectrometry and 2Dgel electrophoresisResponsible for the androgen-insensitive phenotypeSerumMay effect the level of estrogen and therefore the occurrence of endometriosis12 women of reproductive age, 6 with laparoscopically proven endometriosis, and 6 without endometriosis[73]

Carbonic anhydrase 1/mass spectrometry and 2Dgel electrophoresisInvolved with the process of bio-respirationSerumDecreased in patients with endometriosis12 women of reproductive age, 6 with laparoscopically proven endometriosis, and 6 without endometriosis[73]

Actin family proteins (actin related protein 6 and actin-like-7-alpha)/mass spectrometry and 2D-gel electrophoresisActin is in the cellular cytoskeleton and involved in mitosis, signal transduction, and motility.SerumDifferentially expressed in endometriosis12 women of reproductive age, 6 with laparoscopically proven endometriosis, and 6 without endometriosis[73]

CD166 antigen/mass spectrometry and 2D-gel electrophoresisCell adhesion molecules that bind to CD6 and might play a role in T and B cell adhesion to leukocytesSerumDownregulated causing change in immune function of endometriosis patients12 women of reproductive age, 6 with laparoscopically proven endometriosis, and 6 without endometriosis[73]

CyclinA1/mass spectrometry
and 2D-gel electrophoresis
Controls the cell cycle at G1/S and the G2/M stopsSerumDifferentially expressed12 women of reproductive age, 6 with laparoscopically proven endometriosis and 6 without endometriosis[73]

Vimentin/mass spectrometry and 2D-gel electrophoresisA component of the cytoskeleton especially in mesenchymal cellsSerumIncreased in endometriosis tissue as cytoskeletal changes are required12 women of reproductive age, 6 with laparoscopically proven endometriosis, and 6 without endometriosis[73]

B-actin/mass spectrometry and 2D-gel electrophoresisComponent of the cytoskeleton and mediates cell motility and may affect expression of some endometriosis related genesSerumIncreased as cellular changes occur12 women of reproductive age, 6 with laparoscopically proven endometriosis, and 6 without endometriosis[73]

ATP synthase/mass
spectrometry and 2D gel electrophoresis
The production of ATP from ADPSerumIncreased as retrograde menstruation requires ATP12 women of reproductive age, 6 with laparoscopically proven endometriosis and 6 without endometriosis[73]

Glycodelin/2D-gel electrophoresisInvolved in regulating uterine environment for pregnancy and timing the occurrence of fertilization eventsEndometrial tissueIncreased in the eutopic endometrium of patients24 women undergoing laparoscopy either for endometriosis, elective tubal sterilization, or diagnostic purposes. [12]

HSP90/2D-gel electrophoresisChaperone molecule for the correct folding of proteinsEndometrial tissue Decreased expression in eutopic endometrium 24 women undergoing laparoscopy either for endometriosis, elective tubal sterilization, or diagnostic purposes[12]

Annexin A2/2D-gel electrophoresisInvolved in the cytoskeleton and exocytosisEndometrial tissue Decreased in patients showing less secretory activity24 women undergoing laparoscopy either for endometriosis, elective tubal sterilization, or diagnostic purposes.[12]

Peroxiredoxin/2D-gel electrophoresisAntioxidant moleculesEndometrial tissue Altered expression in endometrial tissue24 women undergoing laparoscopy either for endometriosis, elective tubal sterilization, or diagnostic purposes.[12]