**3.1 Steps of spermatogenesis**

The process of spermatogenesis starts at an average age of 12–13 years, continues throughout the remaining life, and markedly decreases during the older age. During the initial stage of spermatogenesis, the spermatogonia shift toward the central

**27**

*Insights of Sperm Pathology and Its Association with Infertility*

lumen of seminiferous tubules. The Sertoli cells are part of a seminiferous tubule and support the process of spermatogenesis. Its main function is to nourish the developing sperm cells throughout the stages of spermatogenesis. Sertoli cells control the entry and exit of nutrients, hormones and other substances into the tubules of the testis. The Sertoli cells are also responsible for establishing and maintaining the spermatogonial stem cell niche, which ensures the renewal of stem cells and the differentiation of spermatogonia into mature germ cells, that progress stepwise through the long process of spermatogenesis, ending in the release of spermatozoa.

Spermatogonia which are able to pass across Sertoli cell layer change and grow in size progressively into primary spermatocytes. The two secondary spermatocytes are formed by meiotic division from the primary spermatocytes. These secondary spermatocytes, also divide to produce spermatids that transform into sperm after a period of time. During the process of spermatocyte to spermatid stage transformation, the 23 pair of chromosomes (46 chromosome total) of spermatocytes also divides, and as a result, 23 chromosomes go to one spermatid and the rest 23 chromosomes to the other spermatid. It takes about 74 days to complete the entire process of spermatogenesis, from spermatogonia to spermatozoa [6] **Figure 2**. Suggested: Round and elongated spermatids will differentiate into mature sperma-

Motility of sperm cells is provided by the back-and-forth movement of tail and it results from rhythmic longitudinal sliding motion between the anterior and posterior tubules [8]. Different molecular markers of sperm, such as mitochondrial membrane potential (MMP), DNA fragmentations and ROS have presently concluded as reliable estimators of sperm function that can be used to evaluate the quality of the sperm [9]. Due to the overloading of ROS, osmatic stress is increased which in turn decreases the MMP and increases the fragmentation of DNA, affecting the viability of sperm [10]. It is broadly accepted that motility of sperm mainly depends upon ATP which is produced by the mitochondria. The latest is located in mid piece of spermatozoa, which explains the correlation between motility and

The spermatozoon is the cell of male reproductive system. Sperm count, also known as sperm concentration, is the parameter to measure the number of sperm cells in the ejaculate. During each coitus the quantity of ejaculated semen in average, is about 3.5 milliliters, and 120 million sperm might be present in average in each milliliter of semen. However, in normal males this count can vary from 35 to 200 million. In several milliliters of each ejaculated semen, an average of total of 400 million sperms might be present. When the sperm count is less than 20 million in 1 milliliter (ml), it might point to infertility. A relatively high sperm count might

There are several causes of infertility in males such as genetic factors like cryptorchidism, congenital absence of vas deferens, karyotype abnormalities and some acquired factors like trauma, varicocele, medication, urogenital infection, inflam-

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

tozoa, by the process of spermiogenesis.

mitochondrial membrane potential [11, 12].

elevate the chances of conception [6].

mation, testicular torsion and idiopathic factors.

**4.1 Sperm count: how much is considered normal?**

**4. Sperm motility**

**3.2 Meiosis**

**Figure 2.** *Steps of spermatogenesis.*

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

lumen of seminiferous tubules. The Sertoli cells are part of a seminiferous tubule and support the process of spermatogenesis. Its main function is to nourish the developing sperm cells throughout the stages of spermatogenesis. Sertoli cells control the entry and exit of nutrients, hormones and other substances into the tubules of the testis. The Sertoli cells are also responsible for establishing and maintaining the spermatogonial stem cell niche, which ensures the renewal of stem cells and the differentiation of spermatogonia into mature germ cells, that progress stepwise through the long process of spermatogenesis, ending in the release of spermatozoa.

### **3.2 Meiosis**

*Innovations in Assisted Reproduction Technology*

The process of spermatogenesis starts at an average age of 12–13 years, continues throughout the remaining life, and markedly decreases during the older age. During the initial stage of spermatogenesis, the spermatogonia shift toward the central

**3.1 Steps of spermatogenesis**

**26**

**Figure 2.**

*Steps of spermatogenesis.*

Spermatogonia which are able to pass across Sertoli cell layer change and grow in size progressively into primary spermatocytes. The two secondary spermatocytes are formed by meiotic division from the primary spermatocytes. These secondary spermatocytes, also divide to produce spermatids that transform into sperm after a period of time. During the process of spermatocyte to spermatid stage transformation, the 23 pair of chromosomes (46 chromosome total) of spermatocytes also divides, and as a result, 23 chromosomes go to one spermatid and the rest 23 chromosomes to the other spermatid. It takes about 74 days to complete the entire process of spermatogenesis, from spermatogonia to spermatozoa [6] **Figure 2**. Suggested: Round and elongated spermatids will differentiate into mature spermatozoa, by the process of spermiogenesis.

### **4. Sperm motility**

Motility of sperm cells is provided by the back-and-forth movement of tail and it results from rhythmic longitudinal sliding motion between the anterior and posterior tubules [8]. Different molecular markers of sperm, such as mitochondrial membrane potential (MMP), DNA fragmentations and ROS have presently concluded as reliable estimators of sperm function that can be used to evaluate the quality of the sperm [9]. Due to the overloading of ROS, osmatic stress is increased which in turn decreases the MMP and increases the fragmentation of DNA, affecting the viability of sperm [10]. It is broadly accepted that motility of sperm mainly depends upon ATP which is produced by the mitochondria. The latest is located in mid piece of spermatozoa, which explains the correlation between motility and mitochondrial membrane potential [11, 12].

### **4.1 Sperm count: how much is considered normal?**

The spermatozoon is the cell of male reproductive system. Sperm count, also known as sperm concentration, is the parameter to measure the number of sperm cells in the ejaculate. During each coitus the quantity of ejaculated semen in average, is about 3.5 milliliters, and 120 million sperm might be present in average in each milliliter of semen. However, in normal males this count can vary from 35 to 200 million. In several milliliters of each ejaculated semen, an average of total of 400 million sperms might be present. When the sperm count is less than 20 million in 1 milliliter (ml), it might point to infertility. A relatively high sperm count might elevate the chances of conception [6].

There are several causes of infertility in males such as genetic factors like cryptorchidism, congenital absence of vas deferens, karyotype abnormalities and some acquired factors like trauma, varicocele, medication, urogenital infection, inflammation, testicular torsion and idiopathic factors.

Semen deficiencies are termed as


### *4.1.1 Oligospermia*

Oligospermia, is one of male infertility causes, defined as low concentration of sperm cells in the ejaculate. Semen with decreased concentration of sperm may often depict considerable abnormalities in morphology and motility of spermatozoa. Low sperm count may be due to an endocrinopathy such as varicocele, prolactinoma or it may be a genetic cause. In about 6 and 15% of patients with severe low sperm count or azoospermia (respectively), microdelitions can be found in azoospermic factor (AZF) region of Y chromosome. AZF refers to one of several proteins or their genes, which are coded from the AZF region located in the human male Y chromosome. Deletions in this region are associated with inability to produce sperm. Subregions within the AZF region are AZFa, AZFb and AZFc, located in the long arm of Y chromosome [13]. By cytogenetic analysis, chromosomal abnormalities were detected in 2% of men having low sperm count and 15–20% with no sperm count. These abnormalities include translocation of nonsex chromosome and Klinefelter syndrome [14].

### *4.1.2 Asthenozoospermia*

Asthenozoospermia, low sperm motility, could be derived due to:


Sperm with the following syndromes: abnormal axoneme, partial or complete lacking of dynein (a family of cytoskeletal motor proteins that move along microtubules in cells and convert the chemical energy stored in ATP to mechanical work), lack of central sheath and lack of inner arms might be unable to show motility;

**29**

*Insights of Sperm Pathology and Its Association with Infertility*

**5. Heritable effect on human sperm structure**

overproduction of reactive oxygen species, might lead to damages in the

**D.** Dysplasia of fibrous sheath spermatozoa: spermatozoa with very short, thick, rigid and immotile tail, mainly due to disorganized and hyperplastic fibrous

The hereditary condition which causes the defects in the flagella of sperm is termed as Kartagener's syndrome, immotile cilia syndrome (ICS), or primary ciliary dyskinesia (PCD). It often leads to chronic respiratory problems, male sterility and situs inversus [19]. These states are linked directly or indirectly with the autosomal recessive traits. The aforementioned conditions make the flagella unable to show normal movement. Sperm with these syndromes have abnormal axoneme lacking dynein arm partially or completely, lack of central sheath, lack of inner arms [20]. Due to variety of defects presented in sperm and cilia, many genes are mutated and contribute to the syndrome [21]. Another flagellar defect characterized by severe asthenozoospermia is familiar as dysplasia of fibrous sheath. In this type of disorder, the sperm have disorganized and hyperplastic fibrous sheath, and very short, thick, rigid and immotile tail [17, 18]. Another flagellar defect which appears in sperm cells of infertile men is known as flagellar dyskinesia [15]. This type of defect was observed in brothers and has been suggested that it arises due to the genetic abbreviation [22]. The sperm consist of altered peri-axonemal structure but have normal axoneme. Densed individual fibers are extended abnormally along the axoneme location and number of longitudinal columns of fibrous sheath are modified and else, there are changes in the order of termination of these structures [15].

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

spermatozoa [16].

sheath [17, 18].

**6. Regulation of sperm motility**

Sperm depicts two kinds of motility:

been shown in this type of motility [23].

circular swimming [24].

hyperactivated motility of sperm.

**6.1 Activation of motility**

a.Progressive motility—typical for newly ejaculated sperm.

cyclic adenosine monophosphate (cAMP) and bicarbonate (HCO3

Spermatozoa acquire the ability of progressive motility in the epididymis. Relatively symmetrical motion of flagella which leads to forward movement has

b.Hyperactivated motility—after sometimes either in reproductive tract of female or in culture, sperm achieves the hyperactivated motility that is characterized by whip like beating of flagellum, asymmetrical flagellar bends and

It is broadly acquired that precious motility of sperm is the chief component of fertility of male. During the beginning of progressive motility and origin of hyper activation of sperm, key factors are involved. These key factors are calcium (Ca2+),

and GABA receptors are the possible candidates which trigger the progressive and

<sup>−</sup>). Olfactory

**C.** Necroozospermia—binding of antisperm antibodies or an increase in white blood cell concentration in the ejaculate, which later results in the *Innovations in Assisted Reproduction Technology*

Semen deficiencies are termed as

b.Aspermia—complete lack of semen.

some and Klinefelter syndrome [14].

*4.1.2 Asthenozoospermia*

syndrome—ICS).

structures [15].

c.Azoospermia—absence of sperm cells in semen.

d.Hypospermia—reduction in the seminal volume.

f. Asthenozoospermia—reduced motility of sperm.

e.Teratospermia—abnormal morphology of sperm cells.

in semen.

*4.1.1 Oligospermia*

a.Oligospermia or oligozoospermia—lower than normal number of spermatozoa

Oligospermia, is one of male infertility causes, defined as low concentration of sperm cells in the ejaculate. Semen with decreased concentration of sperm may often depict considerable abnormalities in morphology and motility of spermatozoa. Low sperm count may be due to an endocrinopathy such as varicocele, prolactinoma or it may be a genetic cause. In about 6 and 15% of patients with severe low sperm count or azoospermia (respectively), microdelitions can be found in azoospermic factor (AZF) region of Y chromosome. AZF refers to one of several proteins or their genes, which are coded from the AZF region located in the human male Y chromosome. Deletions in this region are associated with inability to produce sperm. Subregions within the AZF region are AZFa, AZFb and AZFc, located in the long arm of Y chromosome [13]. By cytogenetic analysis, chromosomal abnormalities were detected in 2% of men having low sperm count and 15–20% with no sperm count. These abnormalities include translocation of nonsex chromo-

Asthenozoospermia, low sperm motility, could be derived due to:

**A.** Inborn metabolic deficiency (such as Kartagener's syndrome or immotile cilia

**B.** Abnormal ultrastructure of the sperm flagellum: as primary ciliary dyskinesia; spermatozoa consist of altered peri-axonemal structure but have normal axoneme. Densed individual fibers are extended abnormally along the axoneme, location and number of longitudinal columns of fibrous sheath are modified and change in the order of termination of these

Sperm with the following syndromes: abnormal axoneme, partial or complete lacking of dynein (a family of cytoskeletal motor proteins that move along microtubules in cells and convert the chemical energy stored in ATP to mechanical work), lack of central sheath and lack of inner arms might be unable to show motility;

**C.** Necroozospermia—binding of antisperm antibodies or an increase in white blood cell concentration in the ejaculate, which later results in the

**28**

overproduction of reactive oxygen species, might lead to damages in the spermatozoa [16].

**D.** Dysplasia of fibrous sheath spermatozoa: spermatozoa with very short, thick, rigid and immotile tail, mainly due to disorganized and hyperplastic fibrous sheath [17, 18].
