Gametogenesis

Gametogenesis is the production of gametes from haploid precursor cells. In animals and higher plants, two morphologically distinct types of gametes are produced (male and female) via distinct differentiation programs. Animals produce a tissue that is dedicated to forming gametes, called the germ line.

Now we are going to learn about the,

1. The Germ Line
2. Sexual Differentiation
3. Spermatogenesis
4. Oogenesis

The Germ Line

The primordial germ cells(PGCs) are the ancestors of the germ line. They are diploid.

In the second week of the human embryo these can be already found in the primary ectoderm (epiblast).

In the third week, the PGCs wander from the primary ectoderm to yolk sac wall. And they collect near the allantois. Now they are extraembryonal.

Between the fourth and the sixth week PGCs wander back into the embryo. They move along the yolk sac wall to the vitelline and into the wall of the rectum. After crossing the dorsal mesentery they colonize the gonadal ridge.

For both sexes the gonads arise in the gonadal ridges. They are generated in the 5th week. At this point, the gonadal ridge represents the primitive gonadal primordium.

Sexual Differentiation

The gender of an embryo is determined at the moment of fertilization and depends on whether the spermatozoon carries an X or a Y chromosome.

In XX embryos the germinal cords do not grow as far as the medulla and the cortical cords envelop the oogonia.

In XY embryos, on the other hand, the medullary cords become the testicular cords that also grow into the depths and establish contact with the mesonephros.

Spermatogenesis

Spermatogenesis is initiated in the male testis with the beginning of puberty.

This comprises the entire development of the spermatogonia (former primordial germ cells) up to sperm cells.

The gonadal cords develop a lumen. They then transform themselves into spermatic canals.

They are termed convoluted seminiferous tubules (Tubuli seminiferi contorti).

They are coated by a germinal epithelium that exhibits two differing cell populations: some are sustentacular cells (= Sertoli’s cells) and the great majority are the germ cells in various stages of division and differentiation.

The maturation of the germ cells begins with the spermatogonia at the periphery of the seminal canal and advances towards the lumen over spermatocytes I (primary spermatocytes), spermatocytes II (secondary spermatocytes), spermatids and finally to mature sperm cells.

The epithelium consists of Sertoli’s sustentacular cells and the spermatogenic cells.

Spermatogenesis is thus accomplished in close contact with the Sertoli’s cells, which not only have supportive and nourishing functions, but also secrete hormones and phagocytize cell fragments.

Along the course of spermatogenesis the germ cells move towards the lumen as they mature. The following developmental stages are thereby passed through:

1. A-spermatogonium
2. B-spermatogonium
3. Primary spermatocyte (= spermatocyte order I)
4. Secondary spermatocyte (= spermatocyte order II)
5. Spermatid
6. Sperm cell (= spermatozoon)

The spermatogenesis can be subdivided into two successive sections:

The first comprises the cells from the spermatogonium up to and including the secondary spermatocyte and is termed spermatocytogenesis.

The second one comprises the differentiation/maturation of the sperm cell, starting with the spermatid phase and is termed spermiogenesis (or spermiohistogenesis).

The approximate 64 day cycle of the spermatogenesis can be subdivided into four phases that last differing lengths of time:

Among the spermatogonia that form the basal layer of the germinal epithelium, several types can be distinguished: 1. Type A cells that undergo homonymous division. 2. Type A cells undergo heteronymous division.

After a further mitotic division type B spermatogonia divide into primary spermatocytes (I) which enter first meiosis.

They then go immediately into the S phase, double their internal DNA.

Following the S phase, these cells attain the complex stage of the prophase of the meiosis and become thereby noticeably visible with a light microscope.

This prophase, which lasts 24 days, can be divided into five sections:

Leptotene
Zygotene
Pachytene
Diplotene
Diakinesis

After the long prophase follow the metaphase, anaphase and telophase that take much less time. One primary spermatocyte yields two secondary spermatocytes.

The secondary spermatocytes go directly into the second meiosis, out of which the spermatids emerge. In the secondary spermatocytes neither DNA reduplication nor a recombination of the genetic material occurs.

Through the division of the chromatids of a secondary spermatocyte, two haploid spermatids arise that contain only half the original DNA content. In a process called spermiogenesis they are transformed into sperm cells with the active assistance of the Sertoli’s cells.

In examining a cross-section of a convoluted seminiferous tubule sometimes it is noticeable that cells appear in groups having the same maturation stages. Because, daughter cells generated by each meiotic step remain bound together by thin cytoplasmic bridges.

Thus with each meiotic step the following generation is twice as large, until the cells have formed a relatively complex network.

The result is that cells of the same development stages are seen there in groups.

Thus, it is highly improbable that all of the development stages will be seen in a single section at the same time. However, not all the spermatogenesis stages are found in a cross-section.

The differentiation of the spermatids into sperm cells is called spermiogenesis. It corresponds to the final part of spermatogenesis and comprises the following individual processes that partially proceed at the same time:

• Nuclear condensation: thickening and reduction of the nuclear size, condensation of the nuclear contents into the smallest space.
• Acrosome formation: Forming a cap (acrosome) containing enzymes that play an important role in the penetration through the pellucid zone of the oocyte.
• Flagellum formation: generation of the sperm cell tail. Four parts of the finished flagellum can be distinguished: The neck, the mid piece, the principle piece, and the tail.
• Cytoplasm reduction: elimination of all unnecessary cytoplasm

Leydig’s interstitial cells are endocrine cells that mainly produce testosterone. An initial active stage of these cells occurs during the embryonic development of the testis.

Oogenesis

Following the immigration of the primordial germ cells into the gonadal ridge, they proliferate. They form germinal cords. Now a cortical zone and a medulla can be distinguished. Because, in females the germinal cords never penetrate into the medullary zone.

In the genital primordium the following processes then take place:

1. A wave of proliferation begins that lasts from the 15th week to the 7th month: primary germ cells arise in the cortical zone.
2. With the onset of the meiosis (earliest onset in the prophase in the 12th week) the designation of the germ cells changes. They are now called primary oocytes. The primary oocytes become arrested in the diplotene stage of prophase I. Shortly before birth, all the foetal oocytes in the female ovary have attained this stage. The meiotic resting phase that then begins is called the dictyotene and it lasts till puberty. Only a few oocytes (secondary oocytes plus one polar body), though, reach the second meiosis and the subsequent ovulation. The remaining oocytes that mature each month become atretic.
3. While the oogonia transform into primary oocytes, they become restructured so that at the end of prophase I (the time of the dictyotene) each one gets enveloped by a single layer of flat, follicular epithelial cells. (oocyte + follicular epithelium = primordial follicle).

The developmental sequence of the female germ cells is as follows:
Primordial germ cell – oogonium – primary oocyte – primary oocyte in the dictyotene
Birth
The continuation of the development / maturation of the oocyte begins again only a few days before ovulation (see fertilization module).

The developmental sequence of a follicle goes through various follicle stages:
Primordial follicle – primary follicle – secondary follicle – tertiary follicle (graafian follicle)
Since a follicle can die at any moment in its development (= atresia), not all reach the tertiary follicle stage.

An ovary is subdivided into cortical (ovarian cortex) and medullary compartments (ovarian medulla).
Both blood and lymph vessels are found in the loose connective tissue of the ovarian medulla.
In the cortical compartment the oocytes are present within the various follicle stages.

The sex hormones influence the primordial follicles to grow and a restructuring to take place. From the primordial follicles the primary follicles, secondary follicles, and tertiary follicles develop in turn. Only a small percentage of the primordial follicles reach the tertiary follicle stage – the great majority meet their end beforehand in the various maturation stages. Large follicles leave scars behind in the cortical compartment and the small ones disappear without a trace.
The tertiary follicles get to be the largest and, shortly before ovulation, can attain a diameter up to 2.5 mm through a special spurt of growth. They are then termed graafian follicles.

During the foetal period, the count of germ cells in the female organism is subject to large variations. These arise due to the fact that the phases of proliferation and decomposition of oocytes take place partially stepwise and partially in parallel.

The normal, common fate of a follicle or female germ cell is known as atresia – ovulation represents an exceptional destiny.

The number of germ cells decreases from the 20th week in order that they are all gone by about 50 years of age. Even though the decrease actually proceeds continuously, three moments in the life of a woman are apparent in which this takes place more rapidly. The largest decrease occurs in the 20th week after the maximum number of 7 million germ cells (per ovary) is reached, thus still in the foetal period. Immediately following birth a further, short period of accelerated decline happens. The third, temporally longest period, of increased decline takes place during puberty.

One terms the decline or the regression of follicles of each stage at every time in the life of a woman follicular atresia. These follicles do not ovulate and the name is derived from that fact. Follicle atresia occurs more intensely, though, at certain moments (foetal period, early postnatal, begin of the menarche).

Of the roughly 500’000 follicles that are present in the two ovaries at the beginning of sexual maturity, only around 480 reach the graafian follicle stage and are thus able to release oocytes (ovulation). Ovulation represents an exceptional fate of a follicle.

Cyclic changes in the hormonal cycle are responsible for the periodicity of the ovulation. In a woman, the rhythmic hormonal influence leads to the following cyclic events:

1. the ovarian cycle (follicle maturation) that peaks in the ovulation and the subsequent luteinization of the granulose cells
2. cyclic alterations of the endometrium that prepare the uterine mucosa so fertilized oocytes can “nest” there. In the absence of implantation, the mucosa will be eliminated (menstrual bleeding).

In the centre of this hormonal control is the hypothalamamics-hypophysial (pituitary gland) system with the two hypophysial gonadotropins FSH and LH. The pulsating liberation of GnRH by the hypothalamus is the fundamental precondition for a normal control of the cyclic ovarian function.

This cyclic activity releases FSH and LH, both of which stimulate the maturation of the follicles in the ovary and trigger ovulation. During the ovarian cycle, estrogen is produced by the theca interna and follicular cells (in the so-called follicle phase) and progesterone by the corpus luteum (so-called luteal phase).

As a rule, the ovarian cycle lasts 28 days. It is subdivided into two phases:

• Follicular phase: recruitment of a so-called follicle cohort and, within this, the selection of the mature follicle. This phase ends with ovulation. Estradiol is the steering hormone. Normally, it lasts 14 days, but this can vary considerably!
• Luteal phase: progesteron production by the “yellow body” (= corpus luteum) and lasts 14 days (relatively constant)

During the follicular phase, a cohort of follicles is recruited from which a dominant follicle is selected that will develop into a De Graaf follicle. The cohort of tertiary follicles that will deliver the de Graaf follicle that will ovulate on day 14 of a cycle has started its maturation about 6 months earlier

• The development of the primary follicle into a secondary follicle takes more than 120 days.
• The development of the secondary follicle into a tertiary (or cavitary or antral) follicle takes about 71 days.
• The terminal development of the tertiary follicle into a Graaf’s follicle lasts 2 weeks and starts at D0 of the menstrual cycle and ends at D14 with ovulation. This last phase is dependent on gonadotropins (LH and FSH) and starts as soon as the corpus luteum of the preceding cycle has regressed.

Antru Anthonisamy