Gametogenesis: Spermatogenesis and Oogenesis

Gametogenesis is the process of forming mature gametes or germ cells (ova and sperm). It is an integral part of reproducing new offspring in almost all animal species, especially those that undergo fertilization. 

The formation of sperms (mature male germ cells) is termed spermatogenesis, whereas ova (female germ cells) is termed oogenesis—gametogenesis forms haploid gametes. 

Different hormones control the number of spermatozoa but not the entire cycle during spermatogenesis. However, hormones tightly regulate and control oogenesis. The primordial germ cells convert into gametes during gametogenesis (oogenesis and spermatogenesis). 

In humans, spermatogenesis begins during puberty (10 to 14 years). However, oogenesis begins in the embryonic stage and freezes. So, a female is born with a fixed number of oocytes (usually 1 million), which declines to 200,000 due to atresia until puberty. When a woman reaches her menopause, the ovary lacks oocytes. Spermatogenesis declines with age. 

In humans, spermatogenesis occurs inside the testis, and oogenesis occurs in the ovary. 

Spermatogenesis

It is the process of producing mature male gametes (sperm), which fertilize the female gametes (oocytes). It occurs along the length of each seminiferous tubule of the testis in successive cycles. In humans, it usually begins during puberty until the seminiferous tubules are inactive. New cycles occur regularly (every 2-3 weeks) before the previous ones are completed. 

It requires approximately 64 days to complete. Although it begins during or just before puberty, it continues throughout life, with only a slight decrease in amount during later stages of life. 

The increase in the hormones gonadotropins and testosterone influences the initiation of spermatogenesis. Although hormones influence the initiation and alter the number of gamete cells produced, they do not affect the duration of the cycle.

Approximately 200 million spermatozoa are produced daily in the adult human testes. Chemical carcinogens, chemotherapeutic agents, certain drugs, environmental toxins, irradiation, and extreme temperatures can reduce the number of replicating germ cells or cause chromosomal abnormalities in individual cells.

Steps of Spermatogenesis

It is a continual process divided into three distinct phases: cellular proliferation by mitosis, reduction divisions by meiosis, and cell differentiation by spermiogenesis. 

  1. Mitosis: The primordial germ cells enter the adluminal portion of seminiferous tubules to convert into spermatogonia. Spermatogonia undergoes a series of mitotic cell divisions before entering meiosis. The mitotic cell division changes spermatogonia into primary spermatocytes. 
  2. Meiosis: The first meiotic cell division (Meiosis I) of primary spermatocyte forms diploid secondary spermatocytes. The second meiotic cell division (Meiosis II) produces haploid spermatids. Every four spermatids emerging from a primary spermatocyte have two X and two Y chromosomes. Due to numerous mitosis cycles and two rounds of meiosis, each spermatogonium committed to meiosis should yield 256 spermatids if all cell survives.    
  3. Spermiogenesis: The conversion of spermatids to mature spermatozoa is termed spermiogenesis. Spermatids are small, round, and non-distinctive cells. These spermatids undergo considerable restructuring to form mature spermatozoa. The changes include the formation of a tail, massive loss of cytoplasm, and alterations in the nucleus. The nucleus becomes eccentric and decreases in size, and chromatin becomes condensed. The acrosome, a lysosome-like structure unique to spermatozoa, buds from the Golgi apparatus, flattens and covers most of the nucleus. The centriole near the Golgi apparatus migrates to the caudal pole, forming a long axial filament of nine peripheral doublet microtubules surrounding a central pair. This structure becomes the axoneme or major of the tail. The cytoplasmic content is redistributed and discarded in the form of residual bodies.

Structure of Spermatozoon (Plural: Spermatozoa)

The spermatozoon structure has three parts: a head, a middle piece, and a tail. 

  1. Head: The head, housing the condensed chromatin and the acrosome, plays a pivotal role in fertilization. The acrosome, a key component, contains proteolytic enzymes that remain inactive until the sperm head makes contact with the egg, facilitating the penetration of the sperm through the egg’s membrane.
  2. Middle piece: The middle piece, an extended part of the tail, is home to a spiral sheath of mitochondria. These mitochondria, the powerhouses of the cell, supply the energy required for the sperm’s locomotion and metabolism.
  3. Tail: It is the motile part of the sperm. It consists of a 9+2 microtubule arrangement, typical of cilia or flagella. The entire part is surrounded by a fibrous sheath that provides some rigidity. The movement of the sperm is by a twisting motion of the tail, which involves the interactions between tubulin fibers and dynein side arms. The interactions require ATP and magnesium.  

Oogenesis and Folliculogenesis

Female ovaries release a mature egg or oocyte every month. The follicle is the functional structure in which the primary oocyte develops. It consists of a single oocyte initiated to grow and develop into a single mature oocyte. The maturation occurs only once every menstrual cycle. 

Most follicles in the ovary undergo atresia, but some develop into mature follicles, produce steroids, and ovulate. With the maturation of follicles, oocytes also mature by entering meiosis, creating the proper number of chromosomes in preparation for fertilization. After rupturing, the follicle becomes a corpus luteum. 

Folliculogenesis

Development and maturation of follicles occur during this process. Follicles are in the following physiologic states: resting, growing, degenerating, or ready to ovulate. During every menstrual cycle, the ovaries generate a group of increasing follicles, most of which fail to develop and undergo follicular atresia (death) at some stage of development. 

However, a dominant follicle, a crucial player in this process, generally emerges from the group of developing follicles and ovulates, releasing a mature haploid ovum. Primordial follicles are usually a non-growing resting pool of follicles that get progressively depleted throughout life. By the time of menopause, the ovaries are devoid of all follicles. The primordial ovaries are in the ovarian cortex (periphery of the ovary)

Primary stage

The progression of primordial follicles to the next stage, the primary stage, occurs at a constant and predictable rate throughout fetal, juvenile, prepubertal, and adult life. Once the primordial follicles leave the resting pool, they commit to further development or atresia. Here, the primordial follicle undergoes morphological changes. These changes include the flattening of pre-granulosa cells into cuboidal granulosa cells. These cells proliferate to form a single continuous layer of cells surrounding the oocyte. During this stage, a glassy membrane, the zona pellucida, surrounds the oocyte and serves as the means of attachment through which granulosa communicate with the oocyte. This is the primary follicular stage of development, with a layer of cuboidal granulosa cells and a basement membrane.

Secondary follicular stage

The primary follicles keep growing mainly by the proliferation of their granulosa cells so that several layers of granulosa cells exist in the secondary follicular stage of development. As the secondary follicle grows more profound in the cortex, stromal cells near the basement membrane begin to differentiate into cell layers called the theca interna and theca externa, and a blood supply with lymphatics and nerves forms within the thecal component. The theca interna eventually become flattened, epitheliod, and steroidogneic. The theca externa remains fibroblastic and provides structural support to the developing follicle. Development beyond the primary follicle begins at puberty and continues in a cyclic manner throughout the reproductive years, highlighting the regularity and predictability of the process.

Tertiary follicular stage

Once the follicle grows, the theca layers expand, and fluid-filled spaces or antra develop around the granulosa cells. This early antral stage of follicle development is called the tertiary follicular stage. FSH hormone controls this stage. 

Graffian follicular stage 

As the antra increases in size, a single, large, coalesced antrum develops, pushing the oocyte to the periphery of the follicle and forming a large 2 to 2.5 cm wide Graafian follicle (preovulatory follicle). In the Graafian follicle, there are three distinct compartments. The granulosa cells around the oocyte are called cumulus granulosa cells, cells lining the antral cavity are called antral granulosa cells, and those attached to the basement are called mural granulosa cells. 

Oogenesis

Female germ cells, crucial for the development of the ovary, embark on a significant journey. They develop in the embryonic yolk sac and migrate to the genital ridge. Here, these cells, known as oogonia, actively divide by mitosis, a process of paramount importance. 

From birth to menopause, the number of oocytes in the ovaries undergoes a dramatic reduction. Starting with an estimated 1 million at birth, most of them perish through a process called atresia. By puberty, only 200,000 oocytes remain, and by age 30, a mere 26,000 are left. By the time of menopause, the ovaries are essentially devoid of oocytes, a testament to the natural progression of life. 

Once the mitosis process ceases, they are called primary oocytes. The oocytes enter the meiotic cycle to prepare for producing a haploid ovum, become arrested in the prophase of the first meiotic division, and remain detained until they either die or grow into mature oocytes at ovulation. The oocytes are inside the 20-mm primordial follicle, which may or may not be surrounded by a single layer of flattened (squamous) pre granulosa cells.

Meiosis resumes during the preovulatory phases. 

As mentioned earlier, healthy primary oocytes remain arrested during the first meiosis, specifically in the prophase I of meiosis. When a graafian follicle, a structure of vital importance, is subjected to a surge of gonadotropins (LH and FSH), the oocyte within undergoes the final stages of meiosis, culminating in the production of a mature gamete. 

Maturation occurs by two successive cell divisions, during which the chromosome number reduces, producing haploid gametes. During fertilization, the diploid state is restored by combining with the male gamete. 

Primary oocytes arrested in meiotic prophase 1 (of the first meiosis) duplicate their centrioles and DNA (4n DNA) so that each chromosome has two identical chromatids. The resumption of meiosis I produces secondary oocytes and the first polar body, which is a small, nonfunctional cell. 

The secondary oocytes now remain arrested after the completion of prophase II until fertilization begins (a very short time after the first arrest). So, the secondary oocyte is arrested in metaphase II. Once a spermatozoon penetrates the secondary oocyte during fertilization, the second meiotic cycle resumes, forming a second polar body and fertilized zygote. However, the secondary oocyte degenerates if fertilization does not occur within 24-48 hours.

References

  1. Larose, H., Shami, A. N., Abbott, H., Manske, G., Lei, L., & Hammoud, S. S. (2019). Gametogenesis: A journey from inception to conception. Current topics in developmental biology, 132, 257–310. https://doi.org/10.1016/bs.ctdb.2018.12.006 
  2. Bustos-Obregon, E., Courot, M., Flechon, J. E., Hochereau-de-Reviers, M. T., & Holstein, A. F. (1975). Morphological appraisal of gametogenesis. Spermatogenetic process in mammals with particular reference to man. Andrologia, 7(2), 141–163. https://doi.org/10.1111/j.1439-0272.1975.tb01247.x 
  3. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Sperm. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26914/

Ashma Shrestha

Hello, I am Ashma Shrestha. I had recently completed my Masters degree in Medical Microbiology. Passionate about writing and blogging. Key interest in virology and molecular biology.

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