primordial germ cell

Gametes are derived from primordial germ cells (PGCs) that are formed in the epiblast during the second week and that move to the wall of the yolk sac.

During the fourth week these cells begin to migrate from the yolk sac toward the developing gonads, where they arrive by the end of the fifth week.

Mitotic divisions increase their number during their migration and also when they arrive in the gonad. In preparation for fertilization, germ cells undergo gametogenesis, which includes meiosis, to reduce the number of chromosomes and cytodifferentiation to complete their maturation.

Migration

Primordial germ cells (PGCs) derive from the epiblast, the outer ectodermal layer of the embryo.

Primordial germ cells (PGCs) subsequently move to the yolk sac wall and then migrate along the dorsal mesentery of the hind gut to the gonadal ridge.

During migration, PGCs undergo cell division and, once in the genital ridge (by the end of the 5th week), lose their motility, begin to aggregate and continue to proliferate by mitosis.

In female embryos

In the female embryos, PGCs differentiate to oogonia and continue to divide by mitosis. Shortly before and during the arrival of PGCs, the epithelium of the genital ridge proliferates and the epithelial cells penetrate the underlying mesenchyme forming the primitive sex cords, which surround the oogonia.

During the 7th week the proliferating epithelium gives rise to a second generation of cords, the cortical cords.

At the 10th week some oogonia will arrest their division and differentiate to oocytes.

In the 4th month the cortical cords split into clusters surrounding one or more of the oocytes and the earliest primary follicles appear.

The oocytes increase rapidly in number and by the 5th month of gestation the total number of oocytes in the ovary reaches its maximum.

However, most oocytes undergo apoptosis, their number diminishes and many follicles become atretic.

At birth, the total number of oocytes is estimated to range from 600,000 to 800,000; subsequently the majority of follicles will become atretic and at the beginning of puberty approximately 400,000 follicles will remain and less than 500 will proceed to ovulation.

Germ cell

A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually.

In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells set aside in early development. Instead, germ cells can come from somatic cells in the adult floral meristem.

Multicellular eukaryotes are made of two fundamental cell types. Germ cells produce gametes and are the only cells that can undergo meiosis as well as mitosis. These cells are sometimes said to be immortal because they are the link between generations. Somatic cells are all the other cells that form the building blocks of the body and they only divide by mitosis.

The lineage of germ cells is called "germ line". Germ cell specification begins during cleavage in many animals or in the epiblast during gastrulation in birds and mammals.

After transport, involving passive movements and active migration, germ cells arrive at the developing gonads. In humans, sexual differentiation starts approximately 6 weeks after conception. The end-products of the germ cell cycle are the egg or sperm.

Under special conditions in vitro germ cells can acquire properties similar to those of embryonic stem cells (ES). The underlying mechanism of that change is still unknown. These changed cells are then called embryonic germ cells (EG). Both EG and ES are pluripotent in vitro, but only ES has proven pluripotency in vivo. Recent studies have demonstrated that it is possible to give rise to primordial germ cells from ES.

Specification

There are two mechanisms to establish the germ cell lineage in the embryo.

The first way is called "preformistic" and involves that the cells destined to become germ cells inherit the specific germ cell determinants present in the germ plasm (specific area of the cytoplasm) of the egg (ovum).

The unfertilized egg of most animals is asymmetrical: different regions of cytoplasm contain different amounts mRNA and proteins. By this germ cells obtained by the first divisions of the fertilized egg are characterized by specific molecules of a particular region of the egg cytoplasm. The second way is found in birds and mammals, where germ cells are not specified by such determinants but by signals controlled by zygotic genes.

In mammals, a few cells of the early embryo are induced by signals of neighboring cells to become primordial germ cells. Mammalian eggs are somewhat symmetrical and after the first divisions of the fertilized egg, the produced cells are all totipotent. This means that they can differentiate in any cell type in the body and thus germ cells. Specification of primordial germ cells in the laboratory mouse is initiated by high levels of Bone Morphogenetic Protein (BMPs) signaling, which activates expression of the transcription factors Blimp-1/Prdm1 and Prdm14.

Migration

Primordial germ cells, germ cells that still have to reach the gonads, also known as PGCs, precursor germ cells or gonocytes, divide repeatedly on their migratory route through the gut and into the developing gonads.

Xenopus sp. - In the Xenopus egg, the germ cell determinants are found in the most vegetal blastomeres. These presumptive PGCs are brought to the endoderm of the blastocoel by gastrulation. They are determined as germ cells when gastrulation is completed.

Migration from the hindgut along the gut and across the dorsal mesentery then takes place. The germ cells split into two populations and move to the paired gonadal ridges.

Migration starts with 3-4 cells that undergo three rounds of cell division so that about 30 PGCs arrive at the gonads. On the migratory path of the PGCs, the orientation of underlying cells and their secreted molecules such as fibronectin play an important role.

Mammals - Mammals have a migratory path comparable to that in Xenopus. Migration begins with 50 gonocytes and about 5,000 PGCs arrive at the gonads. Proliferation occurs also during migration and lasts for 3-4 weeks in humans.

PGCs come from the epiblast and migrate subsequently into the mesoderm, the endoderm and the posterior of the yolk sac. Migration then takes place from the hindgut along the gut and across the dorsal mesentery to reach the gonads (4.5 weeks in human beings). Fibronectin maps here also a polarized network together with other molecules.

The somatic cells on the path of germ cells provide them attractive, repulsive, and survival signals. But germ cells also send signals to each other.

In reptiles and birds, germ cells use another path. PGCs come from the epiblast and move to the hypoblast to form the germinal crescent (anterior extraembryonic structure). The gonocytes then squeeze into blood vessels and use the circulatory system for transport. They squeeze out of the vessels when they are at height of the gonadal ridges. Cell adhesion on the endothelium of the blood vessels and molecules such as chemoattractants are probably involved in helping PGCs migrate.
Sex determining region of Y (Sry) gene

The sex of a mammalian individual is determined by the SRY gene on the Y chromosome. It induces the somatic cells of the gonadal ridge to develop into a testis.

SRY is expressed in a small group of somatic cells of the developing gonad and influence these cells to become Sertoli cells (supporting cells in testis). Sertoli cells are responsible for sexual development along a male pathway in many ways. One of these ways involves stimulation of the arriving primordial cells to differentiate into sperm.

In the absence of the SRY gene, primordial germ cells differentiate into eggs. Removing genital ridges before they started to develop into testes or ovaries results in the development of a female, independent of the carried sex chromosome.

Definition: A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually.

In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells set aside in early development. Instead, germ cells can come from somatic cells in the adult floral meristem.

Multicellular eukaryotes are made of two fundamental cell types. Germ cells produce gametes and are the only cells that can undergo meiosis as well as mitosis. These cells are sometimes said to be immortal because they are the link between generations. Somatic cells are all the other cells that form the building blocks of the body and they only divide by mitosis.

The lineage of germ cells is called "germ line". Germ cell specification begins during cleavage in many animals or in the epiblast during gastrulation in birds and mammals.

After transport, involving passive movements and active migration, germ cells arrive at the developing gonads. In humans, sexual differentiation starts approximately 6 weeks after conception. The end-products of the germ cell cycle are the egg or sperm.

Under special conditions in vitro germ cells can acquire properties similar to those of embryonic stem cells (ES). The underlying mechanism of that change is still unknown. These changed cells are then called embryonic germ cells (EG). Both EG and ES are pluripotent in vitro, but only ES has proven pluripotency in vivo. Recent studies have demonstrated that it is possible to give rise to primordial germ cells from ES.

Specification

There are two mechanisms to establish the germ cell lineage in the embryo.

The first way is called "preformistic" and involves that the cells destined to become germ cells inherit the specific germ cell determinants present in the germ plasm (specific area of the cytoplasm) of the egg (ovum).

The unfertilized egg of most animals is asymmetrical: different regions of cytoplasm contain different amounts mRNA and proteins. By this germ cells obtained by the first divisions of the fertilized egg are characterized by specific molecules of a particular region of the egg cytoplasm. The second way is found in birds and mammals, where germ cells are not specified by such determinants but by signals controlled by zygotic genes.

In mammals, a few cells of the early embryo are induced by signals of neighboring cells to become primordial germ cells. Mammalian eggs are somewhat symmetrical and after the first divisions of the fertilized egg, the produced cells are all totipotent. This means that they can differentiate in any cell type in the body and thus germ cells. Specification of primordial germ cells in the laboratory mouse is initiated by high levels of Bone Morphogenetic Protein (BMPs) signaling, which activates expression of the transcription factors Blimp-1/Prdm1 and Prdm14.

Migration

Primordial germ cells, germ cells that still have to reach the gonads, also known as PGCs, precursor germ cells or gonocytes, divide repeatedly on their migratory route through the gut and into the developing gonads.

Xenopus sp. - In the Xenopus egg, the germ cell determinants are found in the most vegetal blastomeres. These presumptive PGCs are brought to the endoderm of the blastocoel by gastrulation. They are determined as germ cells when gastrulation is completed.

Migration from the hindgut along the gut and across the dorsal mesentery then takes place. The germ cells split into two populations and move to the paired gonadal ridges.

Migration starts with 3-4 cells that undergo three rounds of cell division so that about 30 PGCs arrive at the gonads. On the migratory path of the PGCs, the orientation of underlying cells and their secreted molecules such as fibronectin play an important role.

Mammals - Mammals have a migratory path comparable to that in Xenopus. Migration begins with 50 gonocytes and about 5,000 PGCs arrive at the gonads. Proliferation occurs also during migration and lasts for 3-4 weeks in humans.

PGCs come from the epiblast and migrate subsequently into the mesoderm, the endoderm and the posterior of the yolk sac. Migration then takes place from the hindgut along the gut and across the dorsal mesentery to reach the gonads (4.5 weeks in human beings). Fibronectin maps here also a polarized network together with other molecules.

The somatic cells on the path of germ cells provide them attractive, repulsive, and survival signals. But germ cells also send signals to each other.

In reptiles and birds, germ cells use another path. PGCs come from the epiblast and move to the hypoblast to form the germinal crescent (anterior extraembryonic structure). The gonocytes then squeeze into blood vessels and use the circulatory system for transport. They squeeze out of the vessels when they are at height of the gonadal ridges. Cell adhesion on the endothelium of the blood vessels and molecules such as chemoattractants are probably involved in helping PGCs migrate.
Sex determining region of Y (Sry) gene

The sex of a mammalian individual is determined by the SRY gene on the Y chromosome. It induces the somatic cells of the gonadal ridge to develop into a testis.

SRY is expressed in a small group of somatic cells of the developing gonad and influence these cells to become Sertoli cells (supporting cells in testis). Sertoli cells are responsible for sexual development along a male pathway in many ways. One of these ways involves stimulation of the arriving primordial cells to differentiate into sperm.

In the absence of the SRY gene, primordial germ cells differentiate into eggs. Removing genital ridges before they started to develop into testes or ovaries results in the development of a female, independent of the carried sex chromosome.

Pathology

Germ cell tumor is a rare cancer that can affect people at all ages. 2.4 children out of 1 million suffer the disease, and it counts for 4% of all cancers in children and adolescents younger than 20 years old.

Germ cell tumors are generally located in the gonads but can also appear in the abdomen, pelvis, mediastinum, or brain. Germ cells migrating to the gonads may not reach that intended destination and a tumor can grow wherever they end up, but the exact cause is still unknown. These tumors can be benign or malignant.[7]

Induced differentiation from stem cells

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells, as evidenced by gene expression analysis.

See also

 gametogenesis
 oogenesis
 spermatogenesis