Germ Cells

Definition, Formation, Vs Somatic, Function & in Cancer


Definition:  What are Germ Cells?


Essentially, germ cells are the embryonic precursors of egg and sperm cells (gametes) involved in sexual reproduction in animals. In vertebrates, these cells originate outside the embryo in early development before migrating to the reproductive organs of the organism.

For instance, in mice, they originate from pre-gastrulation, post-implantation embryos (an embryo that is yet to attach to the uterine wall). Because they play an important role in the passing down of information from one generation to another, germ cells are referred to as immortal cells in some spheres.

* Given that all cells of an organism are the descendant of primordial germ cells (PGCs), PGCs are often referred to as totipotent.

 

Some of the features of germ cells include:

  • Round or oval in shape
  • Large in size (ranging from 10 to 20 um depending on the organism)
  • Voluminous, eccentrically located nucleus
  • Use amoeboid movement to migrate
  • High alkaline phosphatase activity


Formation and Development of Germ Cells



Specification


As with all the other cells (in somatic tissue) germline development is also highly regulated to ensure that the organism becomes fertile and capable of reproduction. In vertebrates, this process is known as PGC specification (germ cells specification) and is divided into two modes, namely; the inductive mode and germplasm.


* Germ cell specification refers to the process through which germ cells are set aside.

Germplasm - In this mechanism of germ specification, maternally inherited proteins (including RNAs, some organelles etc) are set aside on a specific location in the oocyte or within the early embryo with the instructive information that directs the differentiation of cells into germ cells.

In D. melanogaster, for instance, proteins and RNAs produced by the nurse cells are transported to the oocyte through the cytoplasmic bridges and localize at the posterior of the ooplasm when they attach to the oocyte. Here, the ooplasm become the germplasm and the cells that inherit it during embryogenesis develop to become primordial germ cells.

Based on a number of studies, the loss of germplasm has been associated with the absence or decrease of germ cells thus proving that components of the germplasm are crucial for the development of germ cells.



Induction

As compared to germplasm specification, induction has been shown to be a more common mechanism of germ cell specification for most animals. It is similar to the other mechanisms used for cell specification in the body and involves the induction of germ cells through signals from the extra-embryonic ectoderm.

In the mouse embryo as is the case with many other animal embryos, the extra-embryonic ectoderm sends the signals (Bmp4/8- Bone marrow promoting factor 4/8) to the epiblast (embryo proper) which in turn stimulates the cells at the interphase to develop into primordial germ cells.


Some of the organisms in which germ cells differentiate epigenetically (germplasm is involved) include:

  • Salamanders
  • Various other lizards
  • Mammals (human beings, baboons, etc)
  • Birds

Some of the organisms in which germ cells are produced as a result of induction include:


Development


As germline stem cells, primordial germ cells originate from a small group of cells that are located outside the embryo early on in Embryogenesis (several days or a few weeks depending on the type of organism).

In human beings, the first population of these cells can be found in the endoderm of the dorsal wall located in the yolk sac near the allantois during the third week of embryo development. However, they migrate to this region from the primary ectoderm, which shows that they originate from an extra-embryonic compartment early on in embryogenesis.

In about the fourth week of embryo development, the cells (Primordial Germ Cells) start migrating from the ectoderm and into the embryo thus becoming extraembryonal (located in compartments of the yolk sac known as the endoderm and the mesoderm). From here, (in the next two weeks of embryo development), the germ cells start their migration towards the gonads as they proliferate. 


The migration is divided into three main phases that include:

· Separation phase - Primordial germ cells move from the hindgut epithelium to the mesenchyme.


· Second phase of migration - Using amoeboid movement, Primordial germ cells migrate from the mesenchyme (mesenchymal cells in the dorsal mesentery) towards the genital ridges.


· Colonization phase - This is the last phase of migration where the cells arrive at and populate the gonads (genital ridges).

For the germ cell program to start, the expression of somatic genes is first repressed.


* The proliferation and migration of primordial germ cells has been shown to be influenced by such factors as TGFbeta1 in mice. These factors are released from the genital ridges and influence the cells to migrate to this region.



Characteristics used in the Identification of Germ Cells


In addition to having a large nucleus and being large in size, germ cells also have an irregular outline, high cytoplasm density, and may appear round or oval in shape when viewed under the microscope.

The high alkaline phosphatase activity is observed in the peripheral cytoplasm of the cells.

Specific RNA and proteins like vasa found in the cytoplasm of these cells are used as molecular markers for the detection of primordial germ cells.

Some of the other components of germ cells (ultrastructure) include:

  • Nuage material
  • Ribosome
  • Mitochondria - Round in shape
  • Haphazardly scattered yolk and oil particles in the cytoplasm
  • Germinal cytoplasm/germ plasma


Function



Gametes: The development of germ cells to gametes



Before germ cells develop to gametes, they first undergo a number of changes that prepare them to develop to either male or female gametes in males and females respectively.

Based on research studies conducted in 2002, it was revealed that upon arriving at the gonads (male or female gonads) DNA demethylation takes place which removes the methylation marks of imprinted genes that are present on the genomes of the cells. In doing so, primordial germ cells are reset.

This is particularly important because it helps ensure that the new epigenetic marks will reflect the sex of the developing embryo. Following sex determination of the embryo, gene imprints are appropriately reestablished as either maternal or paternal. This process involves the participation of enzymes known as DNA methyltransferases which include methyl groups to some of the cytosine nucleotides.

* In females, the new imprinting takes place following the first stage of meiosis (post-embryonically). However, in males, it happens prior to meiosis.

In the gonads, the number of primordial cells increases through rapid mitotic proliferation. This allows the population of germ cells to increase from a few thousand to several million. Whereas division of female germ cell ceases, male germ cells continue to divide after birth.

With regards to gamete production, the germline formed during embryonic development is involved in the oogenesis (in female) and spermatogenesis (in male). In the female, oogenesis starts with PGCs in the ovaries forming a group of immature germ cells that are known as oogonia.

These cells first undergo a process of cell division known as mitosis until the organism reaches its middle fetal life, After 20 weeks of gestation; some of the cells are destroyed through apoptosis while the rest (primary oocytes) remain dormant before the organism reaches puberty. In males, this process takes place in the testes to produce spermatogonia that are diploid in nature.

* Germ cells, which are diploid, go through mitosis to produce spermatogonium/oogonium and ultimately the primary spermatocyte/oocyte. Primary spermatocytes and oocytes, however, have to go through the reductive division cycle known as meiosis.

While both the primary oocyte and spermatocyte go through two meiotic phases, the meiotic processes of spermatocytes produce four haploid cells (sperm cells) while a single haploid egg is produced through the meiotic processes of the primary oocyte. 


* Whereas diploid cells (e.g. primordial germ cells) have two sets of chromosomes (2n) diploid cells (e.g. mature sperm cells), only have one set of chromosomes (n).


* When haploid gametes (egg from the female and sperm cell from the male) unite, they produce a diploid zygote that continues to develop to form a new individual. Given that the zygote is the product of gamete union, they contain a set of chromosomes from both the male and female.


Germ Cells Vs Somatic Cells


Early on in embryo development, the germline cells are set apart from the soma cells. Once this separation occurs, it is not reversible and each group of cells proceeds to their respective pathways.

In some organisms, this separation has been shown to occur in adulthood. Regardless, this separation is important not only because it ensures that the adult organism is fertile and capable of passing genetic material to the next generation, but also because it ensures that the germline cells develop normally.

Somatic and germ cells, therefore, are different types of cells that are differentiated by several characteristics. For instance, as compared to germ cells, somatic cells are, for the most part, regular body cells involved in asexual reproduction.

As such, they are regular cell types other than reproductive cells. They are produced through mitosis which results in the production of identical daughter cells that contain two sets of homologous chromosomes (2n) and are therefore diploid cells. Each cell produced through mitosis (mitotic cells), therefore, will resemble the parent cell.

* A few species have shown to contain haploid somatic cells.

Unlike somatic cells which build the multicellular body of the organism through mitotic division, germ cells undergo cell division to produce gametes which are haploid and involved in sexual reproduction.

Unlike somatic cells which are made up the majority of cells; given that they are arranged into different types of body tissues, germ cells are fewer in number as they are primarily involved in the production of gametes.

* While the two types of cells have several differences, they also share several similarities - both are diploid in a majority of animals which means that they have two sets of homologous chromosomes. On the other hand, they both differentiate into specific types of cells that serve specific roles in the body. 


Germ Cells in Cancer/Tumor


In the event that primordial germ cells are misdirected and end up lodging in extragonadal regions (commonly known as extragonadal sites), they usually die because they cannot perform their function in sites other than the gonads.

However, in some cases, some of the germ cells survive and develop into tumors. Such defects as malformations of the nervous system and the genitoutinary tract etc can increase the risk of tumors along the midline path (the path that germ cells follow before arriving at the gonads).

Although germ cell tumors are rare (making up between 2 and 4 percent of all cancers in children and teenagers) several types of germ cell tumors have been identified.


These include:


Gonadal germ cell tumors

These are the type of tumors that develop in the reproductive organ (gonad) of the child such as:

Ovarian germ cells - For the most part, ovarian germ cell tumors have been shown to develop in one ovary among girls between the ages of 10 and 14. In the event that they are cancerous, these ovarian germ cell tumors are referred to as dysgerminoma.

Although these tumors develop in the ovary, they are also capable of spreading to other parts of the body (malignant tumors). In most cases, however, these tumors are noncancerous and develop into cysts known as teratomas.

Testicular germ cell tumors - A majority of the testicular cancers have been shown to start in the germ cells. These cancers are common in teenagers and younger men.


Testicular cancer is divided into two main categories that include:


Seminoma

Tumors that are 100 percent seminoma are different from the next category of testicular cancers. Although it largely affects the testicles, it is, in a few cases, found in some of the other extra-gonadal locations including the mediastinum. Compared to some of the other testicular cancers, seminoma is very curable with the highest survival rate.

Non-seminama

Non-seminoma is divided into several types of cancer including:

· Yolk sac tumor - Also known as endodermal sinus tumors, yolk sac tumors commonly affect the testicles and ovaries and tend to spread rapidly to other parts of the body (e.g. lymph nodes).

· Teratoma - This type of tumor occurs when primordial cells are misdirected. Their development results in the formation of growths that contain such differentiated tissues as hair, skin, and cartilage among. These types of tumors are mostly found in such sites as the oral and sacrococcygeal region. 

· Embryonal carcinoma - This type of cancer occurs when the cancer cells of the tumor mix with other types of germ cell tumors causing them to be cancerous. It is characterized by the presence of primitive epithelial cells with marked pleomorphism.

· Choriocarcinoma - This type of cancer is common in the uterus and affects cells that form the placenta.


Extracranial Extragonadal Germ Tumors


Germ cell tumors that do not specifically occur in the gonads are known as extracranial extragonadal germ tumors. As such, they start in the sperm and eggs cells and spread to other parts of the body away from gonads.

They do not reach the brain. They are therefore common along the midline which runs from the pineal gland to the coccyx. The mediastinum, the central part of the chest, is the most common site of these tumors in early childhood.

Some of the treatments used to treat germ cell tumors/cancers include:

  • Surgery to remove the cancerous cells/tissue
  • Chemotherapy - The use of drugs to kill cancer cells and prevent them from spreading to the other parts of the body
  • Radiation - This involves the use of X-rays to kill cancerous cells


Read more here about Cell Division and Apoptosis

Return to Cancer Cells info.

Return to learning about Sperm Cells

Return from Germ Cells to MicroscopeMaster home





References



Cassandra G. Extavour and Michael Akam (2003). Mechanisms of germ cell specification across the metazoans: epigenesis and preformation. 

Cynthia R. Wagner. (2010). Germ Cells and Epigenetics. Nature Masterclass. 

Inbar Maayan. (2011). Meiosis in Humans. 

Mark Van Doren. (2011). The Cell Biology of the Germ Cell Life Cycle. NCBI Resources.

Pritesh Krishnakumar and Roland Dosch. (2018). Germ Cell Specification: The Evolution of a Recipe to Make Germ Cells. 

Telma Maria Tenório Zorn. (2002). Primordial germ cells migration: morphological and molecular aspects. ResearchGate. 


Links 


https://embryology.med.unsw.edu.au/embryology/index.php/Primordial_Germ_Cell_Development

https://www.stanfordchildrens.org/en/topic/default?id=germ-cell-tumors-90-P02725

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