Myoid cells of seminiferous tubules

Myoid cells of seminiferous tubules 

 

 

Definition : A peritubular myoid (PTM) cell is one of the smooth muscle cells which surround the seminiferous tubules in the testis

Ultrastructure: Myoid cells have a basal lamina and large numbers of actin filaments.

They also exhibit a significant amount of rough endoplasmic reticulum (rER), a feature indicating their role in collagen synthesis in the absence of typical fibroblasts.

Features:

1.     PTM cells are derived from mesonephric cells

2.     PTM cells are spindle shaped and

3.     They  form several thin elongated layers, approximately 5-7 cell layers, and surround Sertoli cells.

4.     Blood vessels and extensive lymphatic vasculature as well as Leydig cells are present external to the myoid layer.

5.     These are detected in the lamina propria of the seminiferous tubule and immunohistochemical studies have shown functional distinctions between these layers. The inner layers have been shown to express desmin, a smooth muscle phenotype, whereas the outer layers express vimentin, a connective tissue phenotype

Functions of myoid cells:  

1.     Rhythmic contractions of the myoid cells create peristaltic waves that help move spermatozoa and testicular fluid through the seminiferous tubules to the excurrent duct system.

2.     Peritubular myoid cells play a crucial role in the self-renewal and maintenance of the spermatogonial stem cell (SSC) population

T lymphocyte and B lymphocyte

T lymphocyte and B lymphocyte 

 T lymphocyte

T lymphocyte develop from bone marrow-derived cells that migrate to the thymus .

They are essential to human defense against infectious organisms and some cancers. There are two main types of T-cells: helper T-cells and killer T-cells. Helper T-cells stimulate B-cells to make antibodies and help killer cells develop. Killer T-cells directly kill cells that have already been infected by a foreign invader. T-cells also use cytokines as messenger molecules to send chemical instructions to the rest of the immune system to ramp up its response. Activating T-cells against cancer cells is the basis behind checkpoint inhibitors, a relatively new class of immunotherapy drugs that have recently been federally approved to treat lung cancer, melanoma and other difficult cancers. Cancer cells often evade patrolling T-cells by sending signals that make them seem harmless. Checkpoint inhibitors disrupt those signals and prompt the T-cells to attack the cancer cells.

B lymphocyte

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype.

 They function in the humoral immunity component of the adaptive immune system by secreting antibodies.

Additionally, B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines

 In mammals, B cells mature in the bone marrow, which is at the core of most bones.

 In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, (B for bursa) and not from bone marrow as commonly believed.

B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on their cell membrane

 BCRs allow the B cell to bind to a specific antigen, against which it will initiate an antibody response

While both are critical to the body's defense against disease and infection, T-cells and B-cells play very different roles. CART therapy and checkpoint inhibitors are examples of how researchers are using what they’ve learned about T-cells specifically in developing new cancer treatments. But as their differences and similarities show, both types of immune cells employ important natural defenses in helping the body fight cancer.

 

 Summary of T Lymphocyte and B lymphocyte 

topic	T lymphocyte	B lymphocyte
Origin	Bone marrow	Bone marrow
Mature	Thymus	Bone marrow
Location of mature cell	Mature cell present within the lymph node	Mature cell present out side the lymph node
Receptors	Bear TCR receptors	Bear BCR receptor
Viral antigens	Recognized viral antigens on the outside of infected cells	Recognized  antigens on the surface of bacteria and viruses
Life span	Long	Short
Type of immunity	Cell mediated immunity	Humoral or Antibodies mediated immunity
Types of active cell	Cytotoxic T cell , Helper T cell and suppressor / regulatory T cells and memory cells	Plasma cell and memory cells
Surface antigens	Lack of surface antigen	Have surface antigen
Secrete	Lymphokines	Antibodies
%	80% are T lymphocyte	20% are B lymphocyte
Site of infection	Move to the site of infection	Does not move to the site of infection
Tumor cell	Act against tumor cell or transplant	Do not act against tumor cell or transplant
Effect on immune system	Inhibitory effect on immune system	No inhibitory effect on immune system
Functions	·         Lyse virus infected cells and cancer cells ·         Provides immunity against most viruses and few bacteria ·         Aid B cell in antibodies production ·         Modulate immune response	Help eliminate free foreign invaders by enhancing innate immune responses against them Provide immunity against most bacteria and few viruses

Summary of sertoli cell

Seminiferous Epithelium/ sertoli cells

Sertoli cells, also known as supporting, or sustentacular,cells.

The Sertoli cells are important for the function of the testes.

These cells are elongated pyramidal cells that partially envelop cells of the spermatogenic lineage. The bases of the Sertoli cells adhere to the basal lamina, and their apical ends frequently extend into the lumen of the seminiferous tubule.

 In the light microscope, the outlines of Sertoli cells appear poorly defined because of the numerous lateral processes that surround spermatogenic cells .

Studies with the electron microscope reveal that these cells contain abundant smooth endoplasmic reticulum, some rough endoplasmic reticulum, a well-developed Golgi complex, and numerous mitochondria and lysosomes. The nucleus, which is often triangular in outline, possesses numerous infoldings and a prominent nucleolus; it exhibits little heterochromatin

Adjacent Sertoli cells are bound together by occluding junctions at the basolateral part of the cell, forming a blood testis barrier .

The spermatogonia lie in a basal compartment that is situated below the barrier. During spermatogenesis, some of the cells resulting from division of spermatogonia somehow traverse these junctions and come to lie in the adluminal compartment situated above the barrier.

Spermatocytes and spermatids lie within deep invaginations of the lateral and apical margins of the Sertoli cells, above the barrier. As the flagellar tails of the spermatids develop, they appear as tufts extending from the apical ends of the Sertoli cells.

 

Sertoli cells are also connected by gap junctions that provide ionic and chemical coupling of the cells; this may be important in coordinating the cycle of the seminiferous epithelium described above

Sertoli cells in humans and in other animals do not divide during the reproductive period. They are extremely resistant to adverse conditions such as infection, malnutrition, and x-irradiation and have a much better rate of survival after these insults than do cells of the spermatogenic lineage.

Sertoli cells have several functions:

·        Support, protection, and nutritional regulation of the developing spermatozoa. As mentioned above, the cells of the spermatogenic series are interconnected via cytoplasmic bridges. This network of cells is physically supported by extensive cytoplasmic ramifications of the Sertoli cells. Because spermatocytes, spermatids, and spermatozoa are isolated from the blood supply by the blood–testis barrier, these spermatogenic cells depend on the Sertoli cells to mediate the exchange of nutrients and metabolites. The Sertoli cell barrier also protects the developing sperm cells from immunological attack (discussed below).

·        Phagocytosis. During spermiogenesis, excess spermatid cytoplasm is shed as residual bodies. These cytoplasmic fragments are phagocytosed and digested by Sertoli cell lysosomes.

·        Secretion. Sertoli cells continuously secrete into the seminiferous tubules a fluid that flows in the direction of the genital ducts and is used for sperm transport. Secretion of an ABP by Sertoli cells is under the control of follicle-stimulating hormone (FSH) and testosterone and serves to concentrate testosterone in the seminiferous tubule, where it is necessary for spermatogenesis.

·        Sertoli cells can convert testosterone to estradiol. They also secrete a peptide called inhibin, which suppresses synthesis and release of FSH in the anterior pituitary gland

·        Production of the anti-mullerian hormone. Anti- mullerian hormone (AMH, also called mullerian-inhibiting hormone), a glycoprotein that is a member of the transforming growth factor- family, acts during embryonic development to promote regression of the mullerian (paramesonephric) ducts in the male fetus; testosterone fosters the development of structures derived from the Wolffian (mesonephric) ducts.

·        The blood testis barrier. The existence of a barrier between the blood and the interior of the seminiferous tubules accounts for the fact that few substances from the blood are found in the testicular fluid. The testicular capillaries are fenestrated and permit passage of large molecules. Spermatogonia have free access to materials found in blood. However, occluding junctions between the Sertoli cells form a barrier to the transport of large molecules along the space between Sertoli cells. Thus, the more advanced stages of spermatogenesis are protected from blood-borne products protecting male germ cells against blood-borne noxious agents.

·        Production of inhibin B. Inhibin B inhibits the production of FSH by the hypophysis.

 

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Blood testis barrier : lecture note

Blood testes barrier

Definition :

The blood–testis barrier is a physical barrier between the blood vessels and the seminiferous

tubules of the testes.

The name "blood-testis barrier" is misleading in that it is not a blood- organ barrier in a strict sense,

but is formed between Sertoli cells of the seminiferous tubule and as such isolates the further

developed stages of germ cells from the blood.

A more correct term is the "Sertoli cell barrier" (SCB).

To understand blood testes barrier , you have to understand structure of seminiferous tubule of

testes first.

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Each testis possesses approximately 500 sperm-producing seminiferous tubules (30 to 70 cm long and 150 to 250 m in diameter) embedded in a loose vascular connective tissue. The connective tissue wall of each seminiferous tubule, called the tunica propria, is surrounded by a basal lamina.

The tunica (lamina) propria, also called peritubular tissue, is a multilayered connective tissue that lacks typical fibroblasts. In man, it consists of three to five layers of myoid cells (peritubular contractile cells) and collagen fibrils, external to the basal lamina of the seminiferous epithelium (see Fig. 22.6). At the  ltrastructural level, myoid cells demonstrate features associated with smooth muscle cells, including a basal lamina and large numbers of actin filaments. They also exhibit a significant amount of rough endoplasmic reticulum (rER), a feature indicating their role in collagen synthesis in the absence of typical fibroblasts. Rhythmic contractions of the myoid cells create peristaltic waves that help move spermatozoa

and testicular fluid through the seminiferous tubules to the excurrent duct system. Blood vessels and extensive lymphatic vasculature as well as Leydig cells are present external to the myoid layer. As a normal consequence of aging, the tunica propria increases in thickness. This thickening is accompanied by a decreased rate of sperm production and an overall reduction in the size of the seminiferous tubules. Excessive thickening of the tunica propria earlier in life is associated with infertility

The thick seminiferous epithelium (germinal epithelium) is composed of two different epithelial types: Sertoli (supporting) cells and spermatogenic cells that are in the process of differentiation to form spermatozoa. Sertoli cells (Fig. 21.3) are tall columnar cells that possess large clear indented nuclei, abundant mitochondria, well-developed smooth endoplasmic reticulum, Golgi bodies, endolysosomes, and many

cytoskeletal elements. The occluding junctions formed between adjacent Sertoli cells subdivide the lumen of the  eminiferous tubule into:

• A basal compartment, basal to the tight junctions, which is exposed to the underlying vascular connective tissue

• An adluminal compartment, which is isolated from the vascular connective tissue, establishing a blood-testis barrier and protecting the developing gametes from being exposed to the immune system, which would otherwise mount an

immune response against the developing gametes

The functions of Sertoli cells are to:

• S upport, protect, and nourish developingspermatogenic cells

• Phagocytose cell remnants (residual bodies)discarded during the process of spermiogenesis

• Facilitate the release of mature spermatids into the lumen of the seminiferous tubules via actin-mediated contraction (spermiation)

• S ecrete:• Androgen binding protein (ABP) into the seminiferous tubule lumen, increasing testosterone concentration in the seminiferous tubules

• Inhibin, which hinders the release of FSH

• Fructose-rich fluid, which nourishes and transports spermatozoa along the genital ducts

• Testicular transferrin to assist in providing iron to maturing gametes

• Antimüllerian hormone, during embryonic development, which prevents the formation of the female reproductive system and permits the development of the male reproductive system

The Sertoli cell–to–Sertoli cell junctional complex is the site of the blood–testis barrier.

The existence of a barrier between the blood and the interior of the seminiferous tubules accounts for the fact that few substances from the blood are found in the testicular fluid. The testicular capillaries are fenestrated and permit passage of large molecules. Spermatogonia have free access to materials found in blood. However, occluding junctions between the Sertoli cells form a barrier to the transport of large molecules along the space between Sertoli cells. Thus, the more advanced stages of spermatogenesis are protected from blood-borne products protecting male germ cells against blood-borne noxious agents.

This barrier is essential in creating a physiologic compartmentalization within the seminiferous epithelium with respect to ionic, amino acid, carbohydrate, and protein composition. Therefore, the composition of the fluid in the seminiferous tubules and excurrent ducts differs considerably from the composition of the blood plasma and testicular lymph. Plasma proteins and circulating antibodies are excluded from the lumen of the seminiferous tubules. The exocrine  secretory products of the Sertoli cells (particularly the androgen-binding protein (ABP), which has a high binding affinity for testosterone and DHT) are highly concentrated in the lumen of the seminiferous tubules and maintain a high concentration of testosterone, which provides a favorable microenvironment for the differentiating spermatogenic cells.

Most important, the blood–testis barrier isolates the genetically different and therefore antigenic haploid germ cells (secondary spermatocytes, spermatids, and sperm) from the immune system of the adult male. Antigens produced by, or specific to, the sperm are prevented from reaching the systemic circulation. Conversely, _-globulins and specific spermantibodies found in some individuals are prevented from reaching the developing spermatogenic cells in the seminiferous

tubule (Folder 22.3). Therefore, the blood–testis barrier serves an essential role in isolating the spermatogenic cells from the immune system.

Seminiferous Epithelium/ sertoli cells

Seminiferous Epithelium/ sertoli cells
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The seminiferous epithelium is composed of sustentacular Sertoli cells and a stratified layer of developing malegametes. Sertoli cells establish a blood-testis barrier by forming occluding junctions with each other, thus subdividing the seminiferous tubule into adluminal and basal compartments. The basal compartment houses spermatogonia A (both light and dark), spermatogonia B, and the basal aspects of Sertoli cells.

 The adluminal compartment contains the apical portions of Sertoli cells, primary spermatocytes, secondary spermatocytes, spermatids,and spermatozoa. Spermatogenic cells, which regularly replicate and differentiate into mature sperm. These cells are derived from primordial germ cells originating in the yolk sac that colonize the gonadal ridges during early development of the testis.

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Leydig cells (interstitial cells)

Leydig cells (interstitial cells) are large, polygonal, eosinophilic cells that typically contain lipid droplets Lipofuscin pigment is also frequently present in these cells as well as distinctive, rod-shaped cytoplasmic crystals, the crystals of Reinke.

Like other steroid-secreting cells, Leydig cells have an elaborate smooth endoplasmic reticulum (sER), a feature that accounts for their eosinophilia . The enzymes necessary for the synthesis of testosterone from cholesterol are associated with the sER. Mitochondria with tubulovesicular

cristae, another characteristic of steroid-secreting cells, are also present in Leydig cells.

Leydig cells differentiate and secrete testosterone during early fetal life. Secretion of testosterone is required during embryonic development, sexual maturation, and reproductive

function:

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• In the embryo, secretion of testosterone and other androgens is essential for the normal development of the gonads in the male fetus.

At puberty, secretion of testosterone is responsible for the initiation of sperm production, accessory sex gland secretion, and development of secondary sex characteristics.

• In the adult, secretion of testosterone is essential for the maintenance of spermatogenesis and of secondary sex characteristics, genital excurrent ducts, and accessory sex glands.

The Leydig cells are active in the early differentiation of the male fetus and then undergo a period of inactivity beginning at about 5 months of fetal life. Inactive Leydig cells are difficult to

distinguish from fibroblasts. When Leydig cells are exposed to gonadotropic stimulation at puberty, they again become androgen-secreting cells and remain active throughout life.

Seminiferous tubules of testes

Seminiferous tubules of testes 

The testes have an unusually thick connective tissue capsule, the tunica albuginea. An unusually thick, dense connective tissue capsule, the tunica albuginea, covers each testis

 The inner part of this capsule, the tunica vasculosa, is a loose connective tissue layer that contains blood vessels. Each testis

is divided into approximately 250 lobules by incomplete connective tissue septa that project from the capsule. Along the posterior surface of the testis, the tunica albuginea thickens and projects inward as the mediastinum testis. Blood vessels, lymphatic vessels, and the genital excurrent ducts pass through the diastinum as they enter or leave the testis.

Each lobule consists of several highly convoluted seminiferous tubules.

Each lobule of the testis consists of one to four seminiferous tubules, in which sperm are produced, and a connective tissue stroma, in which Leydig (interstitial) cells are contained

The seminiferous tubules consist of a seminiferous epithelium surrounded by a tunica propria.

Each seminiferous tubule is approximately 50 cm long (range, 30 to 80 cm) and 150 to 250 _m in diameter. The seminiferous epithelium is an unusual and complex stratified epithelium composed of two basic cell populations:

• Sertoli cells, also known as supporting, or sustentacular,cells. These cells do not replicate after puberty. Sertoli cells are columnar cells with extensive apical and lateral processes that surround the adjacent spermatogenic cells and occupy the spaces between them.

Seminiferous Tubules

Each highly convoluted seminiferous tubule is composed of a fi bromuscular tunica propria, which is separated from the seminiferous epithelium by a basal membrane.

Seminiferous Epithelium

The seminiferous epithelium is composed of sustentacular Sertoli cells and a stratifi ed layer of developing malegametes. Sertoli cells establish a blood-testis barrier by forming occluding junctions with each other, thus subdividing the seminiferous tubule into adluminal and basal compartments. The basal compartment houses spermatogonia A (both light and dark), spermatogonia B, and the basal aspects of Sertoli cells. The adluminal compartment contains the apical portions of Sertoli cells, primary spermatocytes, secondary spermatocytes, spermatids,and spermatozoa. Spermatogenic cells, which regularly replicate and differentiate into mature sperm. These cells are derived from primordial germ cells originating in the yolk sac that colonize the gonadal ridges during early development of the testis.

2. Tunica Propria: The tunica propria consists of loose collagenous connective tissue, fi broblasts, and myoid cells. The tunica (lamina) propria, also called peritubular tissue, is a multilayered connective tissue that lacks typical fibroblasts. In man, it consists of three to five layers of myoid cells (peritubular contractile cells) and collagen fibrils, external to the basal lamina of the seminiferous epithelium . At the ultrastructural level, myoid cells demonstrate features associated with smooth muscle cells, including abasal lamina and large numbers of actin filaments. They also exhibit a significant amount of rough endoplasmic reticulum (rER), a feature indicating their role in collagen synthesis in the absence of typical fibroblasts. Rhythmic contractions of the myoid cells create peristaltic waves that help move spermatozoa and testicular fluid through the seminiferous tubules to the excurrent duct system. Blood vessels and extensive lymphatic vasculature as well as Leydig cells are present external to the myoid layer.

As a normal consequence of aging, the tunica propria increases in thickness. This thickening is accompanied by a decreased rate of sperm production and an overall reduction in the size of the seminiferous tubules. Excessive thickening of the tunica propria earlier in life is associated with infertility.

C. Stroma

The loose vascular connective tissue stroma surrounding seminiferous tubules houses small clusters of large, vacuolated-appearing endocrine cells, the interstitial cells (of Leydig). Leydig Cells

Leydig cells (interstitial cells) are large, polygonal, eosinophilic cells that typically contain lipid droplets Lipofuscin pigment is also frequently present in these cells as well as distinctive, rod-shaped cytoplasmic crystals, the crystals of Reinke.

Like other steroid-secreting cells, Leydig cells have an elaborate smooth endoplasmic reticulum (sER), a feature that accounts for their eosinophilia . The enzymes necessary for the synthesis of testosterone from cholesterol are associated with the sER. Mitochondria with tubulovesicular

cristae, another characteristic of steroid-secreting cells, are also present in Leydig cells.

Leydig cells differentiate and secrete testosterone during early fetal life. Secretion of testosterone is required during embryonic development, sexual maturation, and reproductive

function:

• In the embryo, secretion of testosterone and other androgens is essential for the normal development of the gonads in the male fetus.

At puberty, secretion of testosterone is responsible for the initiation of sperm production, accessory sex gland secretion, and development of secondary sex characteristics.

• In the adult, secretion of testosterone is essential for the maintenance of spermatogenesis and of secondary sex characteristics, genital excurrent ducts, and accessory sex glands.

The Leydig cells are active in the early differentiation of the male fetus and then undergo a period of inactivity beginning at about 5 months of fetal life. Inactive Leydig cells are difficult to

distinguish from fibroblasts. When Leydig cells are exposed to gonadotropic stimulation at puberty, they again become androgen-secreting cells and remain active throughout life.