Table 4 Differentially expressed proteins as a potential biomarker for patients exhibiting high, medium and low ROS levels

O14967

Calmegin

CLGN

Essential for formation of normal spermatozoa. Important role in spermatogenesis, acts as a chaperone for a range of client proteins that are important for sperm adhesion onto the egg zona pellucida and for subsequent penetration of the zona pellucida.

Overexpressed/ High ROS group, Medium ROS group, Low ROS group

Its expression is triggered in case of elevated oxidative stress. Thus, in men with ROS generation above physiological levels (oxidative stress), calmegin overexpression may impair the ability of spermatozoa to bind to the zona pellucida. Hence, it may be a cause of infertility in these men.

[28–30]

P29144

Tripeptidyl-peptidase 2

TPPII

Tripeptidyl peptidase II is a ‘multi-purpose peptidase’ with house-keeping function in intracellular protein degradation and plays a role in several vital cellular processes such as cell division, apoptosis or antigen processing. TPPII regulates sperm function by modifying the levels of tyrosine phosphorylation. It is involved in the fertilization process, and regulates sperm maturation.

Overexpressed/ High ROS group, Medium ROS group, Low ROS group

Overexpression of TPPII in men with ROS generation above physiological levels may modify sperm protein tyrosine phosphorylation levels, such that spermatozoa is unable to undergo protein tyrosine phosphorylation-associated processes such as capacitation, hyperactivation, and acrosome reaction.

[31–33]

Q9GZS0

Dynein intermediate chain 2, axonemal

DNAI2

Part of the dynein complex of respiratory cilia. DNAI2 can result in reduced fertility due to sperm tail abnormalities.

Underexpressed/High ROS group, Medium ROS group, Low ROS group

The underexpression of DHAI2 in men with ROS above physiological levels may contribute to the negative effect of oxidative stress on sperm motility.

[34]

Q15075

Early endosome antigen 1

EEA1, ZFYVE2

Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking.

Uniquely expressed/High ROS group, Medium ROS group, Low ROS group

Its unique expression in the 3 ROS groups suggests that EEA1 may be involved in the failure of acrosome biogenesis, that results in male infertility.

[35–37]

O95757

Heat shock 70 kDa protein 4L

HSPA4L, APG1, OSP94

Apg-1 encodes a heat shock protein belonging to the Hsp110 family and is inducible by a 32 degrees C to 39 degrees C heat shock in somatic cells. In mouse testicular germ cells Apg-1 mRNA is constitutively expressed depending on the developmental stage. It belongs to the HSP110 heat shock gene family and is produced ubiquitously and predominantly in the testis. It is highly expressed in the spermatogenic cells, from late pachytene spermatocytes to post meiotic spermatids. It is required for normal spermatogenesis.

Underexpressed/High ROS group, Medium ROS group, Low ROS group

The underexpression of HSPA4L in men with ROS above physiological levels may disrupt the normal spermatogenesis process which may contribute to infertility seen in these men.

[38]

P05154

Plasma serine protease inhibitor

SERPINA5, PCI, PLANH3, PROCI

SERPINA5 is a heparin-dependent serine protease inhibitor that acts on body fluids and secretions. Serine protease with lys and arg ester bond specificity is involved in the control of sperm motility. SERPINA5 inhibits the serpin acrosin and indirectly protects the component of the male genital tract from being degraded by excessive released acrosin. It also inhibits tissue-and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities and has a control on sperm motility and fertilization.

Underexpressed/High ROS group, Medium ROS group, Low ROS group

Underexpression of SERPINA5 in men with ROS generation above physiological levels suggests that the reduced motility seen in these infertile patients may be due to the serine protease inhibiting action of SERPINA 5.

[39–41]