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. 2023 Feb 23;24(5):4429. doi: 10.3390/ijms24054429

Table 2.

MS-based profiling studies on human SP: major proteomics findings and candidate biomarkers of male infertility disorders using bottom-up and top-down approaches.

References Study Groups Main Findings Candidate Biomarkers Expression Levels Validation Assay
Wang et al., 2009 [29]
  • -

    NZ 1 (n = 20)

  • -

    AS 2 (n = 38)

 45 proteins were ↑ 3 and 56 proteins were ↓ 4 in the AS group.
Most of these proteins originated from the epididymis and prostate.
ITLN1, ADH, ALAD, DJ-1 were suggested as biomarkers for oxidative stress in AS patients
  • -

    ITLN1, ADH and ALAD were ↑ in AS.

  • -

    DJ-1 was ↓ in AS.

 Western Blot (DJ-1)
Drabovich et al., 2011 [25]
  • -

    NZ (n = 12)

  • -

    PV 5 (n = 8)

  • -

    Non-obstructive AZ 6 (n = 10)

 18 biomarkers were identified at differential abundance between NZ, Non-obstructive AZ, and PV.
Some testis-specific proteins (LDHC, TEX101, and SPAG11B) performed with absolute or nearly absolute specificities and sensitivities.
  • -

    TEX101, LDHC, SPAG11B, PTGDS, MUC15, FAM12B were ↓ in PV and Non-obstructive AZ

 Stable-isotope dilution SRM 7
Batruch et al., 2012 [30]
  • -

    NZ (n = 5)

  • -

    Non-obstructive AZ (n = 5)

  • -

    PV (n = 5)
  • -

    34 proteins were ↑ in NZ compared to Non-obstructive AZ men.

  • -

    18 were ↓ in NZ compared to Non-obstructive AZ.

  • -

    59 were ↑ in Non-obstructive AZ compared to PV patients.

  • -

    16 were ↓ in Non-obstructive AZ compared to PV patients.

Many of these proteins are linked to fertility and are involved in sperm capacitation, spermatogenesis and intracellular signaling.
  • -

    STOM, OVCH2, PTGDS, CRISP2, LIPI, LDHC, SERPINA6, CA4, HIST1H2BA, MPO were ↓ in Non-obstructive AZ compared to NZ

  • -

    VAV2, TGM2, SPARC, KIAA0368, EPS8L2, SPARCL1, COL6A2, DDX1, CST2, CST4 were ↑ in Non-obstructive AZ compared to NZ

  • -

    MUC5B, CPVL, CRIM2, SLLC2A5, ELSPBP1, PATE4, LOC642103, SPINT3, COL18A1, BGN were ↑ in Non-obstructive AZ compared to PV

  • -

    HIST1H2BL, FGG, AZU1, MPO, GSTM2, PRELP, ORM1, FLJ11151, FGB, PAEP were ↓ in Non-obstructive AZ compared to PV

 None
Drabovich et al., 2013 [26]
  • -

    NZ (n = 42)

  • -

    Non-obstructive AZ (n = 25)

  • -

    Obstructive AZ (n = 10)

  • -

    PV (n = 42)

 Epididymis-expressed ECM1 and testis-expressed TEX101 were differentially expressed between Obstructive AZ and Non-obstructive AZ patients and may serve as biomarkers of azoospermia
  • -

    ECM1 was ↑ in NZ and Non-obstructive AZ and ↓ in Obstructive AZ men

  • -

    TEX101 was ↑ in NZ and ↓ in Non-obstructive AZ and Obstructive AZ men

 ELISA (ECM1)
Immunohistochemistry analysis (TEX101)
Immuno-SRM assay (TEX101)
Herwig et al., 2013 [31]
  • -

    NZ (n = 11)

  • -

    OAT 8 (n = 11)

 24 proteins were ↑ in the OAT compared to NZ men.
These proteins are mainly involved in metabolism and inflammation, defense, and stress responses		 AACT and ALDR were ↑ in OAT. None
Sharma et al., 2013 [28]
  • -

    NZ (n = 26)

  • -

    TZ 9 (n = 22)

  • -

    OZ 10 (n = 6)

  • -

    OT 11 (n = 10)

 20 proteins were differentially expressed among the 4 groups.
Biological regulation is the main process affected.
  • -

    MUC6, ORM1 precursor and AEG-like isoform 1 precursor were ↓ in TZ

  • -

    CLU isoform 1 was ↓ in the OZ group

  • -

    PAP was ↓ in TZ and OZ

  • -

    PSA isoform 1 preprotein, SEMG I isoform b preprotein were ↑ in OT

  • -

    CST3 was ↓ in OT

  • -

    ZA2G 1 and TIMP-1 precursor were ↑ in OZ

  • -

    PTPRS isoform 1 precursor was ↑ in TZ

  • -

    DJ-1 was ↑ in TZ and OZ

 None
Cadavid et al., 2014 [37]
  • -

    NZ (n = 7)

  • -

    OA 12 (n = 9)

 Ten proteins were identified with a statistical difference between the NZ and OA patients UBE2C, CSTA, DCD, GNAO, IDE, CERU, SLIT2 Isoform 1, UGT 1 precursor, IQGAP1 were ↑ in OA None
Del Giudice et al., 2016 [27]
  • -

    Adolescents without varicocoele (n = 23)

  • -

    Adolescent with varicocele and normal semen analysis (n = 37)

  • -

    Adolescents with varicocele and altered semen analysis (n = 17)
  • -

    Cab45, protein lefty-1, DNase I, PAP2-alpha were suggested as biomarkers of spermatogenesis and homeostasis associated to the control group.

  • -

    IBP-7, HDC, and CRISP-3 were suggested as biomarkers associated to varicocoele. These proteins participate in cell adhesion, immune and defense response.
  • -

    Cab45 was ↓ in varicocoele groups

  • -

    CRISP-3 was ↑ in Adolescents with varicocoele and altered semen analysis.

 Western Blot (Cab45 and CRISP-3)
Saraswat et al., 2017 [34]
  • -

    NZ (n = 7)

  • -

    AS (n = 10)

 429 proteins were differentially expressed between NZ and AS
  • -

    WAC, RANB3, TICN3, PGAM4, DI3L1, DPP3, MP2K5, TERA, TEX14, SLTM were ↓ in AS

  • -

    SPON2, BSPH1, LX15B, PRDX5, MRO2A, PP1B, IL1FS, A1BG, EFCB5 were ↑ in AS

 None
Liu et al., 2018 [35]
  • -

    NZ (n = 10)

  • -

    OA (n = 10)

 22 proteins were ↑ and 20 proteins were ↓ in the OA patients. These proteins were involved in physiological processes, including metabolism, transport, antioxidation and immune response.
  • -

    PSA, ECM1, HE1, PTGDS and CD177 were ↓ in OA.

  • -

    LTF and PIP were ↑ in OA.

 Western Blot (PSA and LTF)
Wu et al., 2019 [32]
  • -

    NZ (n = 3)

  • -

    AS (n = 3)

 29 proteins were differentially expressed between the two groups:
  • -

    22 proteins were ↑ in NZ group

  • -

    7 proteins were ↓ in NZ group.

Most of these proteins are mainly associated with sperm motility, spermatogenesis and male infertility
  • -

    SORD, ANXA2 and KLK2 were ↓ in AS.

  • -

    HSPA2 was ↑ in AS.

 Western Blot (KLK2, HSPA2, SORD, ANAX2)
Barrachina et al., 2019 [33]
  • -

    NZ (n = 4)

  • -

    AS (n = 4)

  • -

    OZ (n = 4)

  • -

    AZ (n = 4)

 6 proteins were differentially expressed among the groups. These proteins are involved in sperm-oocyte binding, fertilization and immune response. CRISP1, NPC2, SPINT3, and ECM1 were ↓ in OZ and AZ IGHG2 was ↑ in NZ ANPEP was ↓ in AS Western Blot (ECM1)
Correnti et al., 2022 [36]
  • -

    NZ (n = 15)

  • -

    Infertile men (AT 13 =2; OAT = 5; TZ = 6; OZ = 2)

 7 peaks were statistically different between NZ and infertile men. All the peaks were ↓ in infertile men compared to NZ:
  • -

    m/z = 2331 (Fragm: 330–349; SEMG I)

  • -

    m/z = 2362 (Fragm: 248–267; SEMG II)

  • -

    m/z = 2482 (Fragm: 195–215; SEMG I)

  • -

    m/z = 2893 (Fragm: 428–453; SEMG I)

  • -

    m/z = 3059 (Fragm: 248–273; SEMG I)

  • -

    m/z = 3083 (Fragm: 248–273; SEMG II)

  • -

    m/z = 3938 (Fragm: 549–582; SEMG II)

 None

1 NZ, normozoospermic. 2 AS, asthenozoospermic. 3 ↑, upregulated. 4 ↓, downregulated. 5 PV, post-vasectomy (simulates obstructive AZ). 6 AZ, azoospermic. 7 SRM, selective reaction monitoring. 8 OAT, oligoasthenoteratozoospermic. 9 TZ, teratozoospermic. 10 OZ, oligozoospermic. 11 OT, oligoteratozoospermic. 12 OA, oligoasthenozoospermic. 13 AT, asthenoteratozoospermic.