Gametogenesis

Gametogenesis is the process of formation of the male and female gametes i.e. the formation of the sperms and ova. It is a process whereby diploid mother sex cells yield haploid gametes with characteristic features. The process involves two different types of cell division, namely mitosis and meiosis in addition to differentiation and change in the cell shape. Formation of the male gamete (sperm) is called spermatogenesis, whereas formation of the female gamete (ovum) is known as oogenesis. Gametogenesis in both males and females commences at puberty.

Spermatogenesis

Spermatogenesis is the process whereby the haploid unique-featured spermatozoa are formed. It takes place within the seminiferous tubules of the testis and commences at puberty. Accordingly, the structure of the testis before puberty differs from its structure after puberty. Before puberty the somniferous tubules of the testis contain only two types of cells; these are the supportive Sertoli cells and spermatogonia. Sertoli cells are large cells with basal nuclei, whereas the spermatogonia are spherical cells with spherical dense nuclei. At puberty the pituitary gland begins to secrete gonadotrophic hormones, namely, the interstitial cell stimulating hormone (ICSH), the follicle stimulating hormone (FSH), and the luteinizing hormone (LH). The ICSH stimulates the interstitial cells of Leydig cell to produce the male sex hormone testosterone. Testosterone acts on Sertoli cells and spermatogonia to initiate spermatogenesis. Spermatogonia undergo mitotic cell divisions and yield two types of cells; type-A and type-B. Type A replace the mother cells and type B are the cells that develop into spermatocytes. Type-A spermatogonia are characterized by pale nuclei containing prominent nucleoli, whereas type-B spermatogonia have dense nuclei that contain no nucleoli. Moreover, type-A spermatogonia have more numerous cytoplasmic organelles. Spermatogonia are undifferentiated male germ cells. They are unipotential stem cells that proliferate and differentiate to give rise to only type of functional cells known as spermatozoa, which are unique haploid cells with a characteristic head and tail. To give rise to spermatozoa, spermatogonia develop by meiotic cell divisions into spermatocytes and then spermatids, which change shape to become spermatozoa.

From birth until the age of four years, the testis is at a static phase where the seminiferous tubules are filled with small cuboidal spermatogonia and Sertoli cells; Leydig cells are inconspicuous. From the age of four years to ten years, the testis is at a growth phase where the seminiferous tubules enlarge, acquire lumina and become tortuous but the cell types remain the same as before. At the age of ten or thereafter, puberty commences and the seminiferous tubules show numerous spermatocytes, spermatids and spermatozoa, in addition to the spermatogonia and Sertoli cells. The lumen often contains numerous threadlike structures, which are the tails of newly formed spermatozoa. Moreover, the spermatogonia are of two types: type-A and type-B.

Fig. 2.1. H&E-stained sections showing features of the somniferous tubules before puberty (left) and after puberty (right). Before puberty the lumen is small and wall cells are mostly spermatogonia. After puberty the wall contains different types of cells, the lumen is wider, and contains numerous threadlike structures, which are the tails of newly formed sperms.  

Spermatogenesis is the process whereby spermatogonia yields spermatozoa. It involves cell divisions of two different types and as well a transformation in the cell shape. The part of spermatogenesis involving cell divisions is called spermatocytogenesis, whereas the other part which involves change in cell shape without cell division is called spermiogenesis. Spermatocytogenesis results in the formation of three different types of known as the primary spermatocytes, secondary spermatocytes and spermatid.

Fig. 2.2. The illustration shows the process of spermatogenesis. The first part spermatogenesis which is a succession of cells divisions, mitosis followed by cell growth and meiosis is called spermatocytogenesis. The second part which involves change in cell shape without cell division is called spermiogenesis.

Fig. 2.3. The illustration shows events of the process of spermatogenesis.

Spermatocytogenesis

Spermatocytogenesis is the first phase of spermatogenesis whereby spermatogonia give rise to primary spermatocytes, then secondary spermatocytes, and then spermatids. It involves cell divisions only and comprises two different types of cells division, known as mitosis and meiosis. Mitosis is that type of cell division whereby somatic cells of body divide, replicate and proliferate. Somatic cells include all body cells except spermatogonia, spermatocytes, oogonia and oocytes. By mitosis a diploid (2N) cell divides and gives rise to two diploid (2N) daughter cells identical to each other and to the mother cell. Any mitotic division is preceded by synthesis of new DNA that leads to doubling the number of the cell chromosomes. Meiosis on the other hand, is found only in sex cells i.e. spermatocytes in the testis and oocytes in the ovary. Meiosis involves two successive cell divisions preceded by only one doubling of the chromosomes, i.e. there is no DNA synthesis and doubling of chromosomes between the two successive meiotic divisions. Accordingly, the cells produced by the second meiotic division are haploid cells (Spermatogonia proliferate by -N cells) possessing half number of chromosomes of somatic cells.

The mother cells for spermatogenesis are the spermatogonia; theses are immature germ cells present in the basal parts of the wall of the seminiferous tubules. Spermatogonia of the adult testis are of two types, type-A and type-B.  Type-A cells undergo mitotic divisions, each dividing cell gives rise to two cells genetically identical to each other. One of the two daughter cells replaces mother cell and remains as a type-A spermatogonium. The other daughter cell, which is known as type-B spermatogonium, proliferates and grows in size yielding primary spermatocytes. Primary spermatocytes enters prophase of the first meiotic division, which is a lengthy process. It is the prophase of the first meiotic division differs from the prophase of mitotic divisions; the S-phase is the phase where synthesis of new molecules of DNA takes place ultimately leading to doubling of the number of chromosomes; thus cells which was a diploid cells that had a two sets of chromosomes (2N) becomes a tetraploid cell (4N) containing four sets of chromosomes. This phase (prophase of meiosis-1) differs from the prophase of other types of cell division in that pairing of the homologous chromosomes takes place. Since each chromosome consists of two chromatids, the process of pairing leads to four chromatid associated together forming chromosomal tetrads. Each of the two arms of the inner adjacent chromatids of the homologous chromosomes meet and cross over each other at point known as the chiasma. During the  next phase (metaphase of meiosis-1) the peripheral segments of the crossed-over arms are exchanged between these two chromatids, thus, an exchange of genetic material takes place between the homologous non-sister chromatids; this helps in shuffling of genes. Failure of separation of these two chromatids from each other during the next phase of division (anaphase) is known as non-disjunction of chromosomes and can  lead to anomalies such as trisomy and monosomy. Trisomy of autosome number 21 causes Down syndrome, whereas monosomy of the sex chromosomes in females (XO) causes Turner syndrome.

The primary spermatocytes completes the first meiotic division giving rise to two secondary spermatocytes which immediately go into the second meiotic division without DNA-replication and divide into two haploid cells, known as spermatids.

Fig. 2.4. The illustration on the left shows the process whereby type-A spermatogonia undergo mitotic divisions giving rise to two types of cells; one of them is a type-A spermatogonium that replaces the mother cell that has divided and the other is a type-B spermatogonium; all are diploid cells. The illustration on the right shows how a type-B spermatogonium (a diploid cell) yields four haploid spermatids by two successive divisions, meiosis-1 and meiosisi-2.  

Chiasma and Genetic Crossing-over

Chiasma is an X-shaped structure that forms between paired homologous chromosomes by a crossover that forms a physical link between non-sister chromatids of the homologous chromosomes; it takes place during prophase of the first meiotic division. Homologous chromosomes are a pair of chromosome of approximately the same length, centromere position, and staining pattern, for genes with the same corresponding loci. One homologous chromosome is maternal i.e. inherited from the mother while the other is paternal, inherited from the father. Formation of chiasmata is followed by the act of genetic crossing over. The phenomenon of genetic crossing over is necessary for the natural selection; it increases the chances of genetic variation between individuals.

Fig. 2.5. The illustrations show the process of chiasma formation between chromatids of a paired homologous chromosome. The paired homologous chromosome is a tetrad made of four chromatids. Chiasma formation led to exchange of chromatid segments and genes.

Spermiogenesis

Spermiogenesis is the process whereby spermatids change shape without cell division giving rise to spermatozoa (sperms). The spherical normal looking spermatids gradually change their shape and form peculiar-shaped motile spermatozoa. The process of spermiogenesis involves changes in the nucleus and the cytoplasm. Of the cytoplasmic organelles, the rough endoplasmic reticulum (rER), Golgi apparatus, the centrioles, and mitochondria play important roles in the process of spermiogenesis. rER synthesize two important enzymes called hyaluronidase and acrosin. The enzymes are stored for a short while within the cisternae of rER and then transported by transfer vesicles to the Golgi apparatus where they condense and form dense granules known as the acrosome granules. These granules coalesce and form vesicle called the acrosomal vesicle. Meanwhile, the nucleus moves one pole of the cell, condenses and assumes an oval shape to form the head of the developing sperm. The acrosomal vesicle moves towards the condensing nucleus and covers the anterior surface of the nucleus -the future sperm head- forming a cover known as the head cap or acrosomal cap. The centrioles then move and occupy the posterior pole of the nucleus opposite to the head cap. One of the centrioles moves towards the cell periphery and the other remains close to posterior nuclear pole. A flagellum or axoneme develops from this centriole and passes caudally to form the sperm’s tail. The mitochondria arrange themselves around the axoneme extending between the two centrioles forming the mitochondrial sheath of the middle piece of the tail. These mitochondrial provide energy required for beating of the tail that facilitates sperm motility. The microtubules gather together and arrange themselves into bundles alongside the condensed nucleus forming the manchettes. Spermatids rid themselves of excess cytoplasm by streaming it down the manchettes. The shed off masses of cytoplasm constitute residual bodies that are phagocytosed by Sertoli cells.

Fig. 2.6. The illustrations demonstrate the process of spermiogenesis.

The Mature Sperm

The mature sperm is also called the spermatozoon. It comprises a head, neck, and tail made of a middle piece and a principal piece. The spermatozzon is a unique-shaped motile cell about 50-5-60um in length that can swim at speed of 20-50um/second. The spermatozoon’s primary function is the fertilization of a mature ovum to yield a zygote. This function is facilitated by the ability of the sperm to move and reach the site where the ovum is present and also its ability to penetrate the membranes surrounding the oocyte. Normally, millions of sperms are produced by the testes daily, each with a lifespan of about 5-7 days.

Fig. 2.7. The illustration shows the parts of the mature spermatozoon.

The sperm head is a condensed nucleus that contains the male genome, i.e. the complete set of DNA strands. Its anterior part is covered by a special covering known as the head cap or the acrosome. The nucleus, its cap and all other parts of the spermatozoon are covered with a plasma membrane (cell membrane) which maintains the sperm shape and carries normal functions of cell plasma membranes. The plasma membrane facilitates fertilization of the ovum by binding to the oocyte cell the membrane – the oolemma. It also participates in the acrosomal reaction, an initial phase of the process fertilization. The sperm plasma membrane is also involved in capacitation that renders the sperm capable of fertilizing the ovum. The acrosomal cap which covers the anterior part of the nucleus is derived from the Golgi apparatus and contains hydrolytic enzymes synthesized in the rER and packed in the Golgi apparatus. There are several enzymes stored with the acrosomal cap that help the sperm head to penetrate into the oocyte and fertilize it. These enzymes include acrosin, hyaluronidase and acid phosphatase.

The sperm neck -also known as the connecting piece of the tail- joins the sperm head and the tail together; it mediate for the coordinated movement of the sperm. It contains the proximal centrioles that gave rise to cilium axoneme. It has a wall made of the usual nine microtubule triplets. During fertilization the proximal tubule passes with the sperm head into the oocyte. It is responsible for formation of the microtubules of the mitotic spindle of the first cleavage division.

Sperm tail has a complex structure; it has a connecting piece, a middle piece, a principle piece and an endpiece.  The connecting piece is the sperm neck that connects the sperm head to the middle piece; it has been describe above.

The middle piece of the sperm tail is characterized by numerous mitochondria arranged spirally around the axoneme forming the mitochondrial sheath which contains about ten windings of mitochondria. Mitochondria of the middle piece provide the energy required for sperm motility.  

The principal piece of the sperm tail consists of the fibrous sheath, the outer dense fibers, and the axoneme, and is surrounded by the plasma membrane. It plays a pivotal role in the sperm motility. The axoneme extends from the neck along the full length of the tail; it generates the propulsive force for the sperm movement. The axoneme is made of microtubules arranged in the 9 + 2 fashion typical of cilia. The  microtubules are the actual molecular machine that generates sperm motility.

Oogenesis

Oogenesis is the process whereby ova -the female gametes- are formed. It is a much simpler process than spermatogenesis as regards morphogenesis and lack drastic changes in shape but is more complicated as regards the enormously long period of time it takes and arrests of the process that take place at two of its stages. Moreover, during oogenesis the oocyte is completely surrounded by protective cells known as the follicular cells.

Unlike spermatogenesis which begins at puberty, oogenesis begins a long time before puberty; it begins before birth (prenatally) during the fetal period but is completed after puberty and only at the time of fertilization. However, similar to spermatocytogenesis oogenesis comprises both mitosis and meiosis. There is no cell shape transformation as in spermiogenesis; instead, the cell grows greatly into a huge cell known as the oocyte or egg cell at the expense of three tiny cells called the polar bodies. A significant feature of oogenesis are two stoppages of meiosis, one in the prophase of the first meiotic division and the other in metaphase of the second meiotic division.

During fetal period primordial germ cells differentiate into oogonia which proliferate by mitosis and enlarge to give rise to primary oocytes. Primary oocytes go into meiosis-1 but the process is arrested in the prophase of the first meiotic division. The arrest takes place during diplotene of meiosis-1 when the homologous chromosomes begin to separate from each other. Meiosis-1 remains arrested as such for years and is not completes until the primary oocyte is about to be released from the ovary during ovulation in the middle of a menstrual cycle. The end result of meiosis-1 are two genetically identical cells, but morphologically quite dissimilar cells. One of the two daughter cells is a huge cell called the secondary oocyte and the other a minute cell made of a nucleus surrounded by a thin rim of cytoplasm and called the first polar body. The secondary oocyte is released from the ovary at the time of ovulation and immediately goes into the 2nd meiotic division without DNA replication. The second meiotic division (meiosis-2) is also arrested but is arrested in the metaphase. The second meiotic division is not completed until a sperm head penetrate the oolemma at the time fertilization. Meiosis-2 also yield daughter cells identical genetically both being haploid, but morphologically dissimilar; one is huge and called the ovum and the other is tiny and called the second polar body. 

Both the primary and secondary oocytes are surrounded by supportive follicular cells. At birth the ovary contains about 400,000 follicles of one type, the primordial follicles. At puberty a group of primordial follicles are recruited to develop into primary, secondary and Graafian follicles. One Graafian follicle reaches maturity, releases its oocyte (secondary oocyte) and transforms into a corpus luteum.

Fig. 2.8. The illustration shows the process of development of a primordial follicle into a huge Graafian follicle, ovulation of a secondary oocyte, and transformation of remnants of the Graafian follicle into a corpus luteum.

The primordial follicle is a small follicle consisting of a primary oocyte surrounded by a single layer of flat follicular cells. Primordial follicles and all other developing and mature follicles are confined to the ovarian cortex. Under the influence of follicle stimulating hormone FSH, the follicular cells enlarge and become cuboidal; a follicle with a single layer of cuboidal cells is a primary follicle. Then the follicular cells proliferate and become multilayered; a follicle surrounded by two or more layers of follicular cells is a secondary follicle. Still under the influence of SFH, the follicular cells become secretory and small spaces containing a fluid (liquor folliculi) appear between the follicular cells. A follicle containing small fluid-filled spaces is known as a tertiary follicle. The fluid-filled spaces coalesce and form a single cavity called the antrum. A follicle containing an antrum known as the Graafian follicle.

Fig. 2.9. The illustration shows the stages of development of ovarian follicles from the primordial follicle to the graafian follicle. The oocyte within all these different types of follicles is a primary oocyte arrested at the prophase of meiosis-1.  

Ovulation

Ovulation is processing whereby a mature dominant Graafian follicle rupture and releases its oocyte outside the ovary into the abdominal cavity where fimbria of the fallopian tube sweep into the lumen. Only one follicle ruptures and the rest undergo apoptosis and degenerate forming atretic follicle. Hundreds of primordial follicles develop as a cohort at the of each ovarian cycle. Only one of them ovulates, so each month a woman loses hundreds of follicles and in three of four decade she depleted of follicles and goes into menopause. Ovulation is regulated by the pituitary gonadotropic hormone FSH and LH (luteinizing hormone). To begin with follicular development is initiated and regulated by FSH until a huge mature Graafian follicle is formed. Granulosa cells of the follicle have receptors for FSH. In response to FSH they proliferate, grow and start to secrete estrogen. After two days of sustained elevation of estrogen levels, a surge of LH occurs and causes an increase in the activity of proteolytic enzymes that weaken the ovarian wall leading to the rupture of the dominant follicle. Then the granulosa cells of the ruptured follicle transform into progesterone producing lutein cells. This newly formed structure made of lutein cells is known as the corpus luteum. If fertilization and pregnancy take place, the corpus luteum remain as a corpus luteum of pregnancy, otherwise it involutes by the end of menstrual cycle.

The end result of oogenesis is haploid cells. The secondary oocyte which is released at the time of ovulation completes the first meiotic division and yields a large cell and a tiny cell; the large cell is the secondary oocyte, and the tiny cell is the first polar body. Each of these two cells immediately enter into the second meiotic division without DNA replication. The secondary oocytes give rise to a large cell called the ovum and a tiny cell called the second polar body. The first polar body gives rise to two tiny cells called second polar bodies.  All of these four cells (the ovum and the three polar bodies) are haloid 1N cells.   

2.10. The illustration shows the process of formation of the female gamete (the ovum) by oogenesis. Proliferation of the germ cells and oogonia takes place by mitosis. Oogonia are diploid cells that grow into primary oocytes, which also diploid 2N cells. The primary replicates its DNA and undergoes the first meiotic division, yielding a secondary oocyte and the first polar body. The secondary oocyte and the first polar body undergo the second meiotic division without DNA replication four haploid (1N) cells, a large ovum and three small second polar bodies. The polar bodies are short lived cells that degenerate in a short time. 

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