Spermatogenesis
Short note on the process of spermatogenesis.
Gametogenesis - Spermatogenesis
It is simply the process of gamete production. It is a biological process in which mature haploid gametes are formed from diploid or haploid precursor cells after cell division and differentiation. In gametogenesis, the meiotic division of diploid germ cells leads to the formation of various gametes, or it may be produced by the mitotic division of haploid germ cells.
Gametogenesis in Animals
The process of gametogenesis occurs in the specific organs named gonads which are testis in males and ovary in females. Both male and female individuals produce gametes, i.e., sperms and ova, respectively, to achieve the success of sexual reproduction.
The gametes are produced from germ cells initially originated in a developing embryo and remain distinct from the rest of the somatic cells. These germ cells are proliferating in gonads via mitosis and lead to gamete formation upon meiotic division.
The variable forms of gametogenesis are because of different sex types.
However, gametes' embryonic development is the same in both males and females before they turn into gametogonia. These gametogonia are successor of primordial germ cells (PGCs) and are originated from the endoderm, while the gonads are mesodermally originated.
Spermatogenesis
Spermatogenesis occurs in the seminiferous epithelium. The seminiferous epithelium consists of Sertoli cells (somatic cells) and several types of germ cells.
The process of spermatogenesis occurs in the seminiferous tubules of the testis. The testis is situated in a pouch-like scrotum to hold them outside the main body because spermatogenesis requires 2-3°C less temperature than normal body temperature.
The cytogenesis concerned with spermatogenesis is known as spermatogenesis.
It is divided into two phases.
Spermatocytogenesis
In seminiferous tubules, the stem cells adjacent to the inner tubule wall divide in a centripetal direction, which means it begins from the outer side and proceeding towards the central region, called a lumen. In humans' testes produces approximately 200-300 million sperms daily, out of which only 100 million become viable, and the complete spermatogenesis takes place in 74 days. The spermatogenesis process starts in seminiferous tubules. The seminiferous tubules have two types of cells.
- Sertoli cell
- Germinal cell (Spermatogonia)
The arrangement of Sertoli cells in the seminiferous tubules divides the seminiferous tubules into two compartments.
- Adluminal compartment
- Basal compartment
Spermatogenesis process in the germ stem cells called type A spermatogonia. Type A spermatogonia lies in the basal compartment of seminiferous tubules.
Figure: Overview of spermatogenesis.
- (A) Formation of syncytial clones (daughter cells whose cytoplasms are connected) of mammalian male germ cells. In mice, there may be 16 type B spermatogonia linked together. In humans, the cytoplasmic linkages are probably limited to four cells.
- (B) The principal cell types of spermatogenesis and the developmental events separating them.
- (C) Cells move from the basal lamina of the seminiferous tubule toward the lumen as development progresses.
Later on, in cytogenesis, these cells move in a spiral manner towards the tubules' lunch.
The initial spermatocytogenesis shows divisions where the nucleus is divided, but the cytoplasm of daughter cells is connected via thin cytoplasmic bridges.
The subsequent Type B spermatogonia again divide mitotically to produce diploid primary spermatocyte. The primary spermatocyte divides meiotically to give else to haploid secondary spermatocyte. Meiosis II occurs in secondary spermatocytes and leads to the generation of spermatids.
Spermatogenesis
Spermiogenesis is the transformation of a spherical spermatid to a sperm-like mature spermatid. It is simply a transformation process in which the spermatids are differentiated into male germ cells.
Nuclear condensation
The protamine protein is expressed in a high amount in a spermatid. Protamine is rich in arginine and has over 60% arginine residue.
During nuclear condensation, the histones are replaced by protamine. Protamines bind more tightly with DNA and make DNA more condense. This leads to shut down of transcription of all genes. The nuclear condensation resulting in very few transcriptions of genes that is approximately 15% of total genes.
Acrosome formation
The vesicles of the Golgi apparatus are merged and invert to form a cap in most part of condensed nucleus. That is known as acrosome. It functions as lysosome (containing enzymes like hyaluronidase and proteases.
Flagellum formation
One of the centrioles of the cell elongates to become the tail of the sperm.
Sperm cells contain a pair of centrioles. One of the centrioles grows out with nine double peripheral microtubules and two singlets in center. At the time of development of acrosomal vesicle, this flagellum primordium lies opposite to it. It has principally three parts i.e., neck, midpiece and tail. The midpiece is wrapped by mitochondrial group and the tail with 9 + 2 axoneme.
Cytoplasm reduction
The unnecessary organelles and cytoplasm of developing spermatids is phagocytized by Sefton cells and disposed in the tubular lumens. Only a small amount of cytoplasm resides in sperm at neck midpiece region.
Figure: Modification of a germ cell to form a mammalian sperm. (A) The centriole produces a long flagellum at what will be the posterior end of the sperm. The Golgi apparatus forms the acrosomal vesicle at the future anterior end. Mitochondria collect around the flagellum near the base of the haploid nucleus and become incorporated into the midpiece (“neck”) of the sperm. The remaining cytoplasm is jettisoned, and the nucleus condenses. The size of the mature sperm has been enlarged relative to the other stages.
Formation of Tail
One of the centrioles of the cell elongates to become the tail of the sperm. A temporary structure called the “manchette” assists in this elongation. During this phase, the developing spermatozoa orient themselves so that their tails point towards the center of the lumen, away from the epithelium.
Figure: Structure of sperm
Spermiation breaks the structures and bonds, anchoring a mature spermatid to a Sertoli cell, so the spermatozoon is released into the tubule lumen and can be washed out of the seminiferous tubule.
Duration
For humans, the entire process of spermatogenesis takes 74 days within including the transport on ductal system, it takes 3 months. Testes produce 200 to 300 million sperms daily.
Sertoli cell
A Sertoli cell or sustentacular cell is a 'nurse' cell of the testes that provide nutrition to developing sperms. FSH receptor are present on Sertoli cell. FSH is released by pituitary gland and stimulate the proliferation of Sertoli cell. This is the main factor behind the enlargement of testis during puberty. Sertoli cells also act as phagocytes, consuming the residual cytoplasm during spermatogenesis.
Sertoli cells secrete the following substances:
- Anti-Mullerian hormone (AMH): Secreted during the early stages of embryonic development. AMH regress the Mullerian duct in male.
- Inhibin and activins: Secreted after puberty and work together to regulate FSH secretion. The inhibin inhibits the secretion of FSH and the activins as the name suggest activates the secretion of FSH.
- Androgen binding protein (Testosterone binding globulin): This protein binds with the testosterone and increase testosterone concentration in the vicinity of seminiferous tubules. The increased concentration stimulates spermatogenesis.
- Estradiol: Aromatase from Sertoli cells convert testosterone to 17 beta-estradiol to direct spermatogenesis.
- Glial cell line-derived neurotrophic factor (GDNF): The self-renewal capability is spermatogonia is ensure by GDNF.
- The Ets related molecule (ERM transcription factor): This maintains the stock of the spermatogonial stem cell in the adult testis blood-testis barrier.
- Sertoli cell form the tight junction with each other to form blood-testis barrier. This protects spermatids from the immune system of the male.
The intercellular adhesion molecules ICAM-1 and soluble ICAM-1 have antagonistic effects on the tight junctions forming the blood-testis barrier. ICAM-2 molecules regulate spermatid adhesion on the apical side of the barrier (towards the lumen). Due to the tight junction the lumen of Sertoli cell is differentiated into two compartments.
Adluminal compartment this is the lumen where mature sperm are found in basal compartment this is that lumen where spermatogonia cell are found. Tight junctions make an Adluminal compartment an immune-privileged site.
Figure: Schematic illustrating the morphological structure of adult Sertoli cells and their interactions with the different germ cells within the seminiferous epithelium. The relative locations of tight junctions between adjacent Sertoli cells, which create the blood–testis barrier (BTB) and divide the seminiferous tubule into basal and adluminal compartments, are indicated.
Sertoli cells are required for male sexual development. During male development, the gene 'SRY' present on Y chromosome activates 'SOX9'. SOX 9 activates fibroblast growth factor-9 (FGF9). The proliferation and differentiation of Sertoli cell is mainly activated by 'FGF9'. The absence of FGF9 tends to cause a female to develop. Once fully differentiated, the Sertoli cell is unable to proliferate. Therefore, once spermatogenesis has initiated, no more Sertoli cells are created.
Hormonal Regulation of spermatogenesis
Leydig's Interstitial Cells
Leydig cells lies between the seminiferous tubules and act as endocrine cells which produce testosterone in the presence of luteinizing hormone (LH). Testosterone is released into the blood. Leydig cells release a class of hormones called androgens (19-carbon steroids). They secrete testosterone, androstenedione and dehydroepiandrosterone (DHEA), when stimulated by the pituitary hormone luteinizing hormone (LH). LH increases cholesterol desmolase activity (an enzyme associated with the conversion of cholesterol to pregnenolone), leading to testosterone synthesis and secretion by Leydig cells. Testosterone & LH initially act during embryonic development and later at puberty age after LH secretion from anterior hypophysis (pituitary).
The testosterone secreted by these cells along with adrenal cortex initiates the maturation of sperm at puberty.
Figure: Hormones control sperm production in a negative feedback system.
Suggested Readings
- Development Biology, Gilberts, 12th Edition
- Instant Notes in Developmental Biology, R.M. Twyman