Power of Proteomics in Linking Oxidative Stress and Female Infertility

Table 3

Proteins identified at different endometrial stages, in IVF and in the embryo.

Protein estimated/proteomic technique	Function	Source	Relation to endometrial receptivity or embryo readiness	Population size	Reference
L-Glutamate NMCA receptor zeta subunit 1/LC-MS/MS	Subunit of a ligand gated channel that is involved in neuron plasticity. Other roles include glutamate mediated toxicity in mitochondria leading to apoptosis	Endometrial tissue	Only expressed in the secretory endometrium	6 samples of endometrial tissue from a tissue bank; 3 from proliferative phase and 3 from secretory phase (as classified by a pathologist)	[46]
FRAT1/LC-MS/MS	Proto-oncogene that activates the WNT pathway. Inhibits apoptosis	Endometrial tissue	Only expressed in the secretory endometrium	6 samples of endometrial tissue from a tissue bank; 3 from proliferative phase and 3 from secretory phase (as classified by a pathologist)	[46]
Myosin light chain kinase 2/LC-MS/MS	Muscle contraction	Endometrial tissue	Only expressed in the secretory endometrium	6 samples of endometrial tissue from a tissue bank; 3 from proliferative phase and 3 from secretory phase (as classified by a pathologist)	[46]
Isopentenyl diphosphate delta-isomerase/LC-MS/MS	Catalyzes a step in the formation of isoprenoids.	Endometrial tissue	Only expressed in the secretory endometrium	6 samples of endometrial tissue from a tissue bank; 3 from proliferative phase and 3 from secretory phase (as classified by a pathologist)	[46]
Macrophage migration inhibitor factor (MIF)/LC-MS/MS	Prevent macrophages from performing their job in the endometrium	Endometrial tissue	Found in all phases of the endometrium	6 samples of endometrial tissue from a tissue bank; 3 from proliferative phase and 3 from secretory phase (as classified by a pathologist)	[46]
Glycodelin/LC-MS/MS	Regulating the uterine cavity for pregnancy	Endometrial tissue	Up-regulated during the secretory phase	6 samples of endometrial tissue from a tissue bank; 3 from proliferative phase and 3 from secretory phase (as classified by a pathologist)	[46]
Stathmin 1/gel electrophoresis and MALDI-MS	Cytoskeleton, intracellular signaling cascade	Endometrial tissue	Decreased during receptive phase	8 fertile women in their reproductive age, during prereceptive and receptive times of the menstrual cycle	[113]
Annexin A2/gel electrophoresis and MALDI-MS	Skeletal development		Increased during receptive phase	8 fertile women, in their reproductive age, during prereceptive and receptive times of the menstrual cycle	[113]
Monoamine oxidase A/gel electrophoresis and MALDI-MS	Electron transport	Endometrial tissue	Increased during receptive phase	8 fertile women in their reproductive age, during prereceptive and receptive times of the menstrual cycle	[113]
Membrane-associated progesterone receptor component; 1/gel electrophoresis and MALDI-MS	Signaling	Endometrial tissue	Decreased during receptive phase	8 fertile women in their reproductive age, during prereceptive and receptive times of the menstrual cycle	[113]
Collagen alpha 1/gel electrophoresis and MALDI-MS	Skeletal development	Endometrial tissue	Increased during receptive phase	8 fertile women, in their reproductive age, during prereceptive and receptive times of the menstrual cycle	[113]
Annexin A4/gel electrophoresis and MALDI-MS	Signal transduction	Endometrial tissue	Increased during receptive phase	8 fertile women in their reproductive age, during prereceptive and receptive times of the menstrual cycle	[113]
Vimentin/gel electrophoresis and MALDI-MS	Cytoskeleton	Endometrial tissue	Decreased during receptive phase	8 fertile women, in their reproductive age, during prereceptive and receptive times of the menstrual cycle	[113]
S100-A10/gel electrophoresis and MALDI-MS	Signal transduction	Endometrial tissue	Increased during receptive phase	8 fertile women in their reproductive age, during prereceptive and receptive times of the menstrual cycle	[113]
Sulfur oxide dismutase	Enzymatic antioxidant	Serum	Increased during ovarian stimulation	15 patients undergoing ovarian stimulation who had PCOS, endometriosis, or unexplained infertility and all went controlled ovarian stimulation	[9]
Paraoxonase 1 (PON1)	Enzymatic antioxidant	Serum	Increased during ovarian stimulation	15 patients undergoing ovarian stimulation who had PCOS, endometriosis, or unexplained infertility and all went controlled ovarian stimulation	[9]
Glutathione peroxidase (GPx)	Enzymatic antioxidant	Serum	Increased during ovarian stimulation	15 patients undergoing ovarian stimulation who had PCOS, endometriosis, or unexplained infertility and all went controlled ovarian stimulation	[9]
Interleukin 6	Acts as both an anti-inflammatory and proinflammatory cytokine	Serum	Increased during ovarian stimulation	15 patients undergoing ovarian stimulation who had PCOS, endometriosis, or unexplained infertility and all went controlled ovarian stimulation	[9]
Apolipoprotein A1/Tandem MS	Component of high density lipoproteins and acceptor of extra-hepatic cholesterol	Embryo culture media	Decreased in secretome of embryos	702 samples analyzed from women undergoing IVF or from egg donor recipients irrespective of age (26–49 years) or reason for infertility	[11]
Leptin/RT-PCR	Regulates energy uptake and expenditure	Endometrial culture	Increased in competent embryos	Embryos and granulose cells from 9 patients after ovarian hyperstimulation and artificial insemination. Human adipose tissue was used as control for leptin levels. Human endometrial and placental tissue was also studied	[114]
HOXA10/RT-PCR	Functions in embryo viability	Ishikawa cells which are well-differentiated endometrial adenocarcinoma cell line	Increased in cells exposed to blastocyst media	Ishikawa cells grown with blastocyst cells and ones that were placed with an embryo not yet in the blastocyst stage	[115]
Lipocalin-1/mass spectrometry	Transport proteins	Blastocyst secretions	Used for non-invasive aneuploidy testing	65 couples undergoing infertility treatment. Samples were pooled for MS into a group that had 100% implantation from euploid blastocysts or media of aneuploid blastocysts. IVF media without an embryo were used as control	[116]
Complement precursor proteins/2D gel electrophoresis, 2D HPLC and MALDI-MS	Part of the innate immune system	Human follicular fluid and plasma	Altered expression during IVF procedures	38 women (24–38 years) undergoing stimulation prior to IVF. All the samples were used from women with 100% success of IVF	[117]
Fibrinogen Beta precursor/2D gel electrophoresis, 2D HPLC and MALDI-MS	Involved in blood clotting cascade	Human follicular fluid and plasma	Altered expression during IVF procedures	38 women (24–38 years) undergoing stimulation prior to IVF. All the samples were used from women with 100% success of IVF	[117]
Antithrombin III precursor/2D gel electrophoresis, 2D HPLC and MALDI-MS	Inactivates the coagulation system	Human follicular fluid and plasma	Altered expression during IVF procedures	38 women (24–38 years) undergoing stimulation prior to IVF. All the samples were used from women with 100% success of IVF	[117]
Heparin-binding epidermal growth factor- (EGF-) like growth factor precursor/SELDI-TOF-MS	Cell-to-cell juxtacrine signaling inhibiting growth activity	Human embryonic cells	Increased in embryos that failed to develop	21 blastocysts at different developmental stages that had been cryopreserved. They were graded as early, expanded, or degenerated embryos	[118]
Cystatin like precursor/SELDI-TOF-MS	Inhibits cysteine proteases involved in implantation	Human embryonic cells	Increased in embryos that failed to develop	21 blastocysts at different developmental stages that had been cryopreserved. They were graded as early, expanded, or degenerated embryos	[118]
Caspase 1 precursor/SELDI-TOF-MS	Involved in cell death	Human embryonic cells	Increased in embryos that failed to develop	21 blastocysts at different developmental stages that had been cryopreserved. They were graded as early, expanded, or degenerated embryos	[118]
Cytochrome c oxidase subunit VIIIa 3/SELDI-TOF-MS	Part of the electron transport chain in mitochondria	Human embryonic cells	Increased in embryos that failed to develop	21 blastocysts at different developmental stages that had been cryopreserved. They were graded as early, expanded, or degenerated embryos	[118]
Ubiquitin/SELDI-TOF-MS	Part of the ubiquitin-proteosome pathway involved in degradation of proteins	Mice and human embryo secretome	Increased in embryonic secretome associated with successful pregnancies	2-cell human embryos and mouse embryos. Mouse embryos were collected after hyperstimulation of mouse and fertilization. Human embryos were obtained from cryopreserved embryos	[119]