**9. Physiological role of ROS in seminal plasma**

Physiological level of ROS plays a significant task in the physiological process such as capacitation, hyperactivation, acrosomal reaction, fusion of sperm and oocyte in order to assure the proper fertilization [56].

### **9.1 Capacitation**

When spermatozoa pass the epididymis, it is supposed to be mature and their activity is checked by different inhibitory factors which are produced by genital duct epithelia. However, at that time sperm is unable to fertilize the ova. Ejaculated mammalian spermatozoa should reside in the female genital tract for several hours before gaining their fertilizability. In humans however, sperm must move out of the seminal plasma immediately after ejaculation and appear

**35**

proteins [63].

*Insights of Sperm Pathology and Its Association with Infertility*

in the fallopian tube within minutes. As soon as sperm cells are moving out of the ejaculate and passing the cervical mucus, they undergo several biochemical changes collectively called capacitation. These changes involve molecules absorbing on, or integrating into, the sperm plasma membrane during epididymal maturation. The removal or alteration of these molecules prepares the sperm toward successful binding, penetration and fertilization with the egg [57]. During the process of capacitation a production of ROS occurs in spermatozoa that initiates various molecular modifications. Firstly, there is an increase in cAMP; in various organisms and varieties of life processes, this cAMP pathway is necessary because it might activate various enzymes and might regulate the expression of genes [58]. cAMP activates the protein kinase A and causes the phosphorylation of PKA substrate like arginine, serine and threonine. This successively leads to the phosphorylation of MEK, threonine-glutamate-tyrosine, and tyrosine phosphorylation of fibrous sheath proteins. This cAMP increase makes the hyperactivation of sperm. Only the hyperactivated spermatozoa undergo acrosomal reaction due to increased motility and acquired all those properties which are necessary for

Hyperactivation is the peculiar condition of sperm motility. The hyperactivation process is significant for lucrative fertilization and it regarded a subcategory of capacitation. Hyperactivated sperm have characteristics of asymmetric flagellar movement, high amplitude, side to side head displacement and also a nonlinear

Hyperactivated spermatozoon binds to zona pellucida after passing the cumulus oophorus, starting the exocytotic discharge of hyaluronidase and proteolytic enzymes, sperm acrosome reaction (AR) induced by oocyte investment, is a prerequisite event for the spermatozoa. It is obligatory for the sperm cell to enable to penetrate the zona pellucida (ZP) and to fuse with the oocyte. Progesterone (P4), secreted by cumulus cells, is an important cofactor for the occurrence of this exocytosis event. The AR results from the fusion between outer acrosomal and plasma membranes leading to inner acrosomal membrane exposure. Binding of agonists, P4 or ZP3 glycoprotein, to plasma membrane sperm receptors activates intraspermatic signals and enzymatic pathways involved in the AR. Among the proteins or glycoproteins described as potential sperm receptors for ZP, Gi/ Go protein-coupled and tyrosine kinase receptors have been described. ZP- and P4-promoted AR is mediated by an obligatory intracellular calcium increase, appearing first at the acrosome equatorial segment and spreading throughout the head. The plasma membrane channels involved in calcium entry are operated by a plasma membrane depolarization and protein phosphorylation mediated by protein kinase C and tyrosine kinase protein. Part of the calcium increase could also be due to intracellular store release through nucleotide (cAMP)-gated channels. Besides adenylate cyclase and phospholipase C activations, intracellular calcium increase also stimulates phospholipase A2 and actin depolymerization, leading to membrane fusion [62]. The sperm cell crosses the physical barrier of zona pellucida and within few minutes it fuses with the oocytes. ROS is involved in the action of the spermatozoa by phosphorylating three plasma membrane

*DOI: http://dx.doi.org/10.5772/intechopen.90950*

fertilization [59, 60].

**9.2 Hyperactivation**

**9.3 Acrosome reaction**

motility [61].

### *Insights of Sperm Pathology and Its Association with Infertility DOI: http://dx.doi.org/10.5772/intechopen.90950*

in the fallopian tube within minutes. As soon as sperm cells are moving out of the ejaculate and passing the cervical mucus, they undergo several biochemical changes collectively called capacitation. These changes involve molecules absorbing on, or integrating into, the sperm plasma membrane during epididymal maturation. The removal or alteration of these molecules prepares the sperm toward successful binding, penetration and fertilization with the egg [57]. During the process of capacitation a production of ROS occurs in spermatozoa that initiates various molecular modifications. Firstly, there is an increase in cAMP; in various organisms and varieties of life processes, this cAMP pathway is necessary because it might activate various enzymes and might regulate the expression of genes [58]. cAMP activates the protein kinase A and causes the phosphorylation of PKA substrate like arginine, serine and threonine. This successively leads to the phosphorylation of MEK, threonine-glutamate-tyrosine, and tyrosine phosphorylation of fibrous sheath proteins. This cAMP increase makes the hyperactivation of sperm. Only the hyperactivated spermatozoa undergo acrosomal reaction due to increased motility and acquired all those properties which are necessary for fertilization [59, 60].
