Spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubules. These cells are called spermatogonial stem cells. The mitotic division of these produces two types of cells. Type A cells replenish the stem cells, and type B cells differentiate into primary spermatocytes. The primary spermatocyte divides meiotically into two secondary spermatocytes; each secondary spermatocyte divides into two equal haploid spermatids by Meiosis II. The spermatids are transformed into spermatozoa by the process of spermiogenesis. These develop into mature spermatozoa, also known as sperm cells. Thus, the primary spermatocyte gives rise to two cells, the secondary spermatocytes, and the two secondary spermatocytes by their subdivision produce four spermatozoa and four haploid cells.
Spermatozoa are the mature male gametes in many sexually reproducing organisms. Thus, spermatogenesis is the male version of gametogenesis, of which the female equivalent is oogenesis. In mammals it occurs in the seminiferous tubules of the male testes in a stepwise fashion. Spermatogenesis is highly dependent upon optimal conditions for the process to occur correctly, and is essential for sexual reproduction. DNA methylation and histone modification have been implicated in the regulation of this process. It starts during puberty and usually continues uninterrupted until death, although a slight decrease can be discerned in the quantity of produced sperm with increase in age.
Spermatogenesis starts in the bottom part of seminiferous tubes and, progressively, cells go deeper into tubes and moving along it until mature spermatozoa reaches the lumen, where mature spermatozoa are deposited. The division happens asynchronically; if the tube is cut transversally one could observe different maturation states. A group of cells with different maturation states that are being generated at the same time is called a spermatogenic wave.
Purpose
Spermatogenesis produces mature male gametes, commonly called sperm but more specifically known as spermatozoa, which are able to fertilize the counterpart female gamete, the oocyte, during conception to produce a single-celled individual known as a zygote. This is the cornerstone of sexual reproduction and involves the two gametes both contributing half the normal set of chromosomes to result in a chromosomally normal zygote.To preserve the number of chromosomes in the offspring – which differs between species – one of each gamete must have half the usual number of chromosomes present in other body cells. Otherwise, the offspring will have twice the normal number of chromosomes, and serious abnormalities may result. In humans, chromosomal abnormalities arising from incorrect spermatogenesis results in congenital defects and abnormal birth defects and in most cases, spontaneous abortion of the developing foetus.
Location in humans
Spermatogenesis takes place within several structures of the male reproductive system. The initial stages occur within the testes and progress to the epididymis where the developing gametes mature and are stored until ejaculation. The seminiferous tubules of the testes are the starting point for the process, where spermatogonial stem cells adjacent to the inner tubule wall divide in a centripetal direction—beginning at the walls and proceeding into the innermost part, or lumen—to produce immature sperm. Maturation occurs in the epididymis. The location is important as the process of spermatogenesis requires a lower temperature to produce viable sperm, specifically 1°-8 °C lower than normal body temperature of 37 °C. Clinically, small fluctuations in temperature, such as from an athletic support strap, cause no impairment in sperm viability or count.Duration
For humans, the entire process of spermatogenesis is variously estimated as taking between 72 and 74 days and approximately 120 days. Including the transport on ductal system, it takes 3 months. Testes produce 200 to 300 million spermatozoa daily. However, only about half or 100 million of these become viable sperm.Stages
The entire process of spermatogenesis can be broken up into several distinct stages, each corresponding to a particular type of cell in humans. In the following table, ploidy, copy number and chromosome/chromatid counts are for one cell, generally prior to DNA synthesis and division. The primary spermatocyte is arrested after DNA synthesis and prior to division.Spermatocytogenesis
Spermatocytogenesis is the male form of gametocytogenesis and results in the formation of spermatocytes possessing half the normal complement of genetic material. In spermatocytogenesis, a diploid spermatogonium, which resides in the basal compartment of the seminiferous tubules, divides mitotically, producing two diploid intermediate cells called primary spermatocytes. Each primary spermatocyte then moves into the adluminal compartment of the seminiferous tubules and duplicates its DNA and subsequently undergoes meiosis I to produce two haploid secondary spermatocytes, which will later divide once more into haploid spermatids. This division implicates sources of genetic variation, such as random inclusion of either parental chromosomes, and chromosomal crossover that increases the genetic variability of the gamete. The DNA damage response machinery plays an important role in spermatogenesis. The protein FMRP binds to meiotic chromosomes and regulates the dynamics of the DDR machinery during spermatogenesis. FMRP appears to be necessary for the repair of DNA damage.During spermatocytogenesis, meiosis employs special DNA repair processes that remove DNA damages and help maintain the integrity of the genome that is passed on to progeny. These DNA repair processes include homologous recombinational repair and non-homologous end joining
Each cell division from a spermatogonium to a spermatid is incomplete; the cells remain connected to one another by bridges of cytoplasm to allow synchronous development. Not all spermatogonia divide to produce spermatocytes; otherwise, the supply of spermatogonia would run out. Instead, spermatogonial stem cells divide mitotically to produce copies of themselves, ensuring a constant supply of spermatogonia to fuel spermatogenesis.
Spermatidogenesis
Spermatidogenesis is the creation of spermatids from secondary spermatocytes. Secondary spermatocytes produced earlier rapidly enter meiosis II and divide to produce haploid spermatids. The brevity of this stage means that secondary spermatocytes are rarely seen in histological studies.Spermiogenesis
During spermiogenesis, the spermatids begin to form a tail by growing microtubules on one of the centrioles, which turns into basal body. These microtubules form an axoneme. Later the centriole is modified in the process of centrosome reduction. The anterior part of the tail thickens because mitochondria are arranged around the axoneme to ensure energy supply. Spermatid DNA also undergoes packaging, becoming highly condensed. The DNA is packaged firstly with specific nuclear basic proteins, which are subsequently replaced with protamines during spermatid elongation. The resultant tightly packed chromatin is transcriptionally inactive. The Golgi apparatus surrounds the now condensed nucleus, becoming the acrosome.Maturation then takes place under the influence of testosterone, which removes the remaining unnecessary cytoplasm and organelles. The excess cytoplasm, known as residual bodies, is phagocytosed by surrounding Sertoli cells in the testes. The resulting spermatozoa are now mature but lack motility. The mature spermatozoa are released from the protective Sertoli cells into the lumen of the seminiferous tubule in a process called spermiation.
The non-motile spermatozoa are transported to the epididymis in testicular fluid secreted by the Sertoli cells with the aid of peristaltic contraction. While in the epididymis the spermatozoa gain motility and become capable of fertilization. However, transport of the mature spermatozoa through the remainder of the male reproductive system is achieved via muscle contraction rather than the spermatozoon's recently acquired motility.
Role of Sertoli cells
At all stages of differentiation, the spermatogenic cells are in close contact with Sertoli cells which are thought to provide structural and metabolic support to the developing sperm cells. A single Sertoli cell extends from the basement membrane to the lumen of the seminiferous tubule, although the cytoplasmic processes are difficult to distinguish at the light microscopic level.Sertoli cells serve a number of functions during spermatogenesis, they support the developing gametes in the following ways:
- Maintain the environment necessary for development and maturation, via the blood-testis barrier
- Secrete substances initiating meiosis
- Secrete supporting testicular fluid
- Secrete androgen-binding protein, which concentrates testosterone in close proximity to the developing gametes
- * Testosterone is needed in very high quantities for maintenance of the reproductive tract, and ABP allows a much higher level of fertility
- Secrete hormones affecting pituitary gland control of spermatogenesis, particularly the polypeptide hormone, inhibin
- Phagocytose residual cytoplasm left over from spermiogenesis
- Secretion of anti-Müllerian hormone causes deterioration of the Müllerian duct
- Protect spermatids from the immune system of the male, via the blood-testis barrier
- Contribute to the spermatogonial stem cell niche