MALE REPRODUCTIVE SYSTEM

MALE REPRODUCTIVE SYSTEM
Reproductive system is as important as well as the human body that is concern with procreation, continuation of life or survival of human species. It is non functional at the early stage of life, although the anatomical structures are already in place but become active at puberty under hormonal influences.

Function of the male reproductive system
1. Production of gametes.
2. Transfer of spermatozoa to the female during coitus
3. Production of sex hormone 

STRUCTURES
Male reproductive system can be divided into:
• Primary sex organ: the primary sex organ in the male is the testis which produces the gamete and secrete male sex hormone(androgens)
• Secondary sex organ: they are responsible for storage and transportation of spermatozoa. They includes:
i. Ducts: epididymis, ductus deferens, ejaculatory ducts and urethra.
ii. Accessory glands: seminal vesicles, prostrate and bulbourethra glands.
iii. Corpulatory organs: penis

Structure-testis, Epididymis and Vas Deferens
The testes are the male gonads, similar to ovaries in females. The human testes are two glandular, ovoid organs that lie in the scrotum enveloped by a strong connective tissue covering, the tunica albuginea. Early in the embryonal life, testes lie retroperitoneally in the abdominal cavity. Before birth, the testes and spermatic cord descend through the inguinal canal into the scrotum.1 each testis contains about 370 seminiferous lobules measuring about 180 μm in diameter each. These lobules lie between the fibrous septa extending between the mediastinum testis and the tunica albuginea. They are enclosed by connective tissue containing Leydig cells, blood vessels, lymphatics and nerves.

ANATOMY AND PHYSIOLOGY OF MALE GAMETOGENESIS 
Along the posterior border, the testes are loosely connected to the epididymis, a narrow, tightly-coiled tube that connects the efferent ducts from the back of each testis to its vas deferens. Spermatozoa produced in the testis are stored in the epididymis to be carried away by the vas deferens. Smooth muscles in the wall of the epididymis contract to thrust the spermatozoa forward into the prostatic urethra. Here sperms mix with secretions from accessory glands including the prostate, seminal vesicles and bulbourethra gland          
                             
SUPPORTING CELLS 
• Leydig cells
• Sertoli cells

LEYDIG CELLS 
Leydig cells, named after the German anatomist Franz Leydig who first identified them in 1850, are somatic cells lying in the testicular interstitium. These are irregularly shaped cells containing granular cytoplasm and are often seen in clumps within the connective tissue. Leydig cells of testis are the main site of synthesis and secretion of androgens, including testosterone, the primary male sex hormone.1 Luteinizing hormone (LH) secreted by the pituitary, stimulates the Leydig cell to produce testosterone, which is then accumulated in the interstitium and seminiferous tubules.

SERTOLI CELLS 
The Sertoli cells line the seminiferous tubules and are the ‘nurse’ cells of the testes. Their main function is to nurture the developing germ cells during various stages of spermatogenesis.4 Sertoli cells communicate with germ cells through multiple sites for the maintenance of spermato-genesis. Sertoli cells also form tight junctions that divide the seminiferous tubules into two compartments for the spermatozoal development. The basal compartment below the tight junctions is in contact with the circulatory system and is the site where spermatogonia develop into primary spermatocytes. The tight junctions open at specific times and allow progression of spermatocytes to the adluminal compartment, where meiosis is completed. In the adluminal compartment, spermatocytes are protected by a blood-testis barrier formed by tight junctions between the Sertoli cells.

The principal functions of Sertoli cells are as follows:
• Provide support for germ cells, forming an environment in which they develop and mature.
• Provide the signals that initiate spermatogenesis and sustain spermatid development.
• Regulate pituitary gland function and, in turn, control of spermatogenesis.
• Secrete aqueous secretion into the lumen to aid sperm transport.

SPERMATOGENESIS 
Spermatogenesis is the process by which male spermato-gonia develop into mature spermatozoa.

During this complex process, primitive totipotent stem cells divide to produce daughter cells, which, over a span of approximately 70 days mature into spermatids. The process involves both mitosis and meiosis and is regulated by Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) from the anterior pituitary.

Spermatogonia divide by mitosis and differentiate until they become primary spermatocytes, which remain dormant until puberty. 

The process of spermatogenesis can be best understood by discussing individual stages. The first stage of formation of spermatozoa is spermatocytogenesis. During this stage, stem cells divide to produce a population of cells destined to become mature sperm cells and to replace themselves. Spermatocytogenesis occurs in the basal compartment.

 Spermatogonium is of three functional types (Figure 1.3)
• Type Ad “dark”
• Type Ap “pale”
• Type B
Type Ad cells maintain the initial pool of spermato-gonium. These cells do not take part directly in the process of spermatid formation but ensure a continuous supply of stem cells for spermatogenesis. Type Ad 

Type Ap spermatogonia undergo repeated mitotic divisions to produce a clone of cells. These cells are tethered together with cytoplasmic bridges that allow synchronized development. The resultant cells differentiate into Type B spermatogonia. Type B spermatagonia undergo mitosis to produce diploid intermediate cells, the primary spermatocytes. The primary spermatocytes are arrested in the prophase of the first meiotic division until puberty and thus have the longest life span of all types of spermatagonia. At puberty, the diploid (2N) primary spermatocytes enter meiosis I and divide by to become haploid (N) secondary spermatocytes. Secondary spermatocytes have the shortest life span (1.1 to 1.7 days) of all types of spermatagonia. Secondary spermatocytes undergo meiosis II to yield spermatozoa (N) with half the DNA material of the primary spermatocytes from which they originated. The process begins with one primary spermatocyte containing double genetic material, which divides into two haploid secondary spermatocytes, each containing normal complement of genetic material and finally resulting in four spermatids, each containing half of the genetic material from the original spermatocyte


Once the process of meiosis is completed, the final stage of spermiogenesis, begins. During this stage the spermatids develop into mature, motile spermatozoa (Figure 1.5). This occurs in deep folds of cytoplasm of the Sertoli cells. The maturation of spermatids to spermatozoa depends on the action of androgens on the Sertoli cells in which the developing spermatozoa are embedded. FSH acts on the Sertoli cells to facilitate the last stages of spermatid maturation.

Six different stages in the process of spermatid maturation are described by morphology:
• Sa-1 and Sa-2
– Golgi complex and mitochondria are well developed and differentiated.
– The acrosomal vesicle appears.
– The chromatin body appears in one pole of the cell opposite from the acrosomal vesicle.
– The proximal centriole and axial filaments appear.
• Sb-1 and Sb-2
– Acrosome formation is completed.
– Intermediate piece is formed.
• Sc-1 and Sc-2
– Tail development is completed during Sc stage.

During the post meiotic phase, progressive condensation of the nucleus occurs with inactivation of the genome, the histones convert to transitional proteins, and protamines convert to well-developed disulfide bond.5 Mature spermatozoa are released from the Sertoli cells and become free in the lumen of the tubules. This process is spermiation. The newly released sperm are non-motile. They are suspended in a fluid secreted by the Sertoli cells and are transported to the epididymis by peristaltic contraction of the myoid cells present in the walls of the tubules. The spermatozoa reach the epididymis by passing through the efferent
ductules, the first segment of the extra-testicular duct system. Within the epididymis, activation of the CatSper protein localized in the principal piece of the sperm tail develops the progressive motility of the sperm. This protein appears to be a Ca2+ ion channel that permits cAMP-generated Ca2+ influx. Smooth muscle peristalsis transports the sperm through the remainder of the male reproductive system.

SPERMATOZOA 
Each sperm is an intricate motile cell, rich in DNA, with a head comprised mostly of chromosomal material (Figure 1.6). Sperm are highly specialized, differentiated and condensed cells that do not divide. Approximately 60 μm long and 1 μm wide, each sperm is composed of the head, midpiece (body), and tail.

HEAD 
The normal head of the spermatozoa is oval and measures about 3.0-5.0 μm in length and 2.0-3.0 μm in width with a thickness of 1.5 μm (Mortimer). The normal length-to-width ratio is about 1.50-1.75 (Anibal AA). The head contains the nuclear material for the fertilization process. The acrosome covers the sperm head like a cap. This lysosome-like organelle is rich in enzymes which mediate the penetration of ovum by the sperm.

NECK 
The neck is the junction between the head and tail. The presence of decapitated spermatozoa is a common abnormality.

TAIL 
The tail contains the locomotory flagellum, divided into middle, principal and end pieces. The middle piece has the flagellum, surrounded by a sheath of mitochondria that provide the energy for movement.

 

HORMONAL REGULATION OF SPERMATOGENESIS
Spermatogenesis is regulated by hormones secreted by the hypothalamicpituitary- gonadal axis. Spermatogenesis is regulated by negative feedback mechanism. Hypothalamus secretes gonadotrophin releasing factor (GnRH) in the hypothalamo-hypophyseal portal circulation. This factor stimulates synthesis and releases the gonadotrophins, FSH and LH, by the pituitary gland into the systemic circulation. LH acts on the Leydig cells stimulating the production of testosterone. FSH acts on the Sertoli cells and is important for the development of the Sertoli cells that are vital for spermatogenesis. Sertoli cells under the influence of the FSH secrete androgen binding protein, inhibin and plasminogen activator. Androgen binding protein (ABG) is necessary to maintain high levels of the androgens locally which is important for spermatogenesis. The plasminogen factor helps in spermiation and inhibin has a negative feedback effect on the FSH secretion by the anterior pituitary gland.
Testosterone is the principle androgen produced by the Leydig cells in the testis under the influence of LH.

Functions of Testosterone
• Differentiation, development and maturation of internal and external reproductive organs in male.
• Stimulation of spermatogenesis.
• Regulation of accessory sex gland functions.
• Development of the secondary sex characters.

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