- Germ cell
Germ cells are progenitors of the
gametes. These singled out cells move through the gut to the developing gonadsand undergo mitotic proliferation followed by meiosisand differentiation into either eggs or sperm (mature gametes). Plants do not have a germ line set aside in early development, instead germ cells can come from somatic cellsin the adult floral meristem. [cite book
title=Molecular biology of the cell
author=Alberts B., Johnson A., Lewis J., Raff M., Roberts K., Walter P.
publisher=New York, Garland Science, 1463 p
year=2002] [cite book
publisher=Oxford, Bios Scientific Publishers, 451p
year=2001] [cite journal
title=Germ cells: The eternal link between generations
publisher=C.R. Biologies 330, 474-478
year=2007] [cite journal
title=Germ cells are forever
author=Cinalli R.M., Rangan P., Lehmann R.
eukaryotesare made of 2 fundamental cell types. Germ cells produce gametes and are the only cells that can undergo meiosis as well as mitosis. These cells are often considered as 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 epiblastduring gastrulationin 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 post conception). The end-products of the germ cell cycle are the egg or sperm. [cite journal
author=Kunwar P.S., Lehmann R.
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. Recent studies have demonstrated that it is possible to give rise to primordial germ cells from ES. [cite journal
title=Evaluating human embryonic germ cells: concord and conflict as pluripotent stem cells
author=Turnpenny L., Spalluto C.M., Perrett R.M., O’Shea M., Hanley K.P., Cameron I.T., Wilson D.I., Hanley N.A.
publisher=Stem Cells 24:212-220
There are 2 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 mRNAand 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 kind of 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.
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.
In the model organism "
Drosophila", pole cells passively move from the posterior end of the embryo to the posterior midgut because of the infolding of the blastoderm. Then they actively move through the gut into the mesoderm. Endodermal cells differentiate and together with Wunen proteins they induce the migration through the gut. Wunen proteins are chemorepellantsthat lead the germ cells away from the endodermand into the mesoderm. After splitting in 2 populations, the germ cells continue migrating laterally and in parallel until they reach the gonads. Columbus proteins, chemoattractants, stimulate the migration in the gonadal mesoderm.
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 blastocoelby gastrulation. They are determined as germ cells when gastrulation is completed. Migration from the hindgut along the gut and across the dorsal mesenterythen takes place. The germ cells split in 2 populations and move to the paired gonadal ridges. Migration starts with 3-4 cells that undergo 3 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 fibronectinplay an important role.
Mammals have a migratory path comparable to that in "Xenopus". Migration begins with 50 gonocytes and about 5000 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 vascular system for transport. They squeeze out of the vessels when they are at height of the gonadal ridges. Cell-adhesion on the
endotheliumof the blood vessels and molecules such as chemoattractants are probably involved in helping PGCs migrate.
ex 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 genital 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.
Details of the development of diploid germ cells into either haploid eggs or sperm (gametogenesis; respectively oogenesis and spermatogenesis) are different for each species but the general stages are similar. Oogenesis and spermatogenesis have many features in common, they both involve:
*Extensive morphological differentiation
*Incapacity of surviving for very long if fertilization does not occurDespite their homologies they also have major differences:
*Spermatogenesis has equivalent meiotic divisions resulting in 4 equivalent spermatids while oogenic meiosis is asymmetrical: only one egg is formed together with 2 polar bodies.
*Different timing of maturation: oogenic meiosis is interrupted at one or more stages (for a long time) while spermatogenic meiosis is rapid and uninterrupted.
After migration primordial germ cells will become oogonia in the forming gonad (ovary). The oogonia proliferate extensively by mitotic divisions, up to 5-7 million cells in humans. But then many of these oogonia die and about 50000 remain. These cells differentiate into primary oocytes. In week 11-12 "post coitus" the first meiotic division begins (before birth for most mammals) and remains arrested in prophase I from a few days to many years depending on the species. It is in this period or in some cases at the beginning of sexual maturity that the primary oocytes secrete proteins to form a coat called
zona pellucidaand they also produce cortical granulescontaining enzymes and proteins needed for fertilization. Meiosis stands by because of the follicular granulosa cellsthat send inhibitory signals through gap junctionsand the zona pellucida. Sexual maturation is the beginning of periodic ovulation. Ovulation is the regular release of one oocyte from the ovary into the reproductive tract and is preceded by follicular growth. A few follicle cells are stimulated to grow but only one oocyte is ovulated. A primordial follicle consists of an epithelial layer of follicular granulosa cells enclosing an oocyte. The pituitary glandsecrete follicle-stimulating hormones (FSHs) that stimulate follicular growth and oocyte maturation. The thecal cellsaround each follicle secrete estrogen. This hormone stimulates the production of FSH receptors on the follicular granulosa cells and has at the same time a negative feedback on FSH secretion. This results in a competition between the follicles and only the follicle with the most FSH receptors survives and is ovulated. Meiotic division I goes on in the ovulated oocyte stimulated by luteinizing hormones (LHs) produced by the pituitary gland. FSH and LH block the gap junctions between follicle cells and the oocyte therefore inhibiting communication between them. Most follicular granulosa cells stay around the oocyte and so form the cumulus layer. Large nonmammalian oocytes accumulate yolk, glycogen, lipid, ribosomes, and the mRNA needed for protein synthesis during early embryonic growth. These intensive RNA biosynthese are mirrored in the structure of the chromosomes, which decondense and form lateral loops giving them a lampbrush appearance. Oocyte maturation is the following phase of oocyte development. It occurs at sexual maturity when hormones stimulate the oocyte to complete meiotic division I. The meiotic division I produces 2 cells differing in size: a small polar body and a large secondary oocyte. The secondary oocyte undergoes meiotic division II and that results in the formation of a second small polar body and a large mature egg, both being haploid cells. The polar bodies degenerate. [cite journal
title=Experimental approaches to the study of primordial germ cell lineage and proliferation
author=De Felici M., Scaldaferri M.L., Lobascio M., Iona S., Nazzicone V., Klinger F.G., Farini D.
publisher=Human reproduction update 10:197-206
journal=Human Reproduction Update
pmid=15140867] Oocyte maturation stands by at metaphase II in most vertebrates. During ovulation, the arrested secondary oocyte leaves the ovary and matures rapidly into an egg ready for fertilization. Fertilization will cause the egg to complete meiosis II. In human females there is proliferation of the oogonia in the fetus, meiosis starts then before birth and stands by at meiotic division I up to 50 years, ovulation begins at puberty.
A 10 - 20 μm large somatic cell generally needs 24 hours to double its mass for mitosis. By this way it would take a very long time for that cell to reach the size of a mammalian egg with a diameter of 100 μm (some insects have eggs of about 1000 μm or greater). Eggs have therefore special mechanisms to grow to their large size. One of these mechanisms is to have extra copies of genes: meiotic division I is paused so that the oocyte grows while it contains 2 diploid chromosome sets. Some species produce many extra copies of genes (some amphibians up to 1 or 2 million copies). Another (complementary) mechanism is partly dependence on syntheses of other cells. In amphibians, birds, and insects yolk is made by the liver (or his equivalent) and secreted into the blood. Neighboring accessory cells in the ovary can also provide nutritive help of 2 types. In some invertebrates some oogonia become
nurse cells. These cells are connected by cytoplasmic bridges with oocytes. The nurse cells of insects provide oocytes macromolecules such as proteins and mRNA. Follicular granulosa cells are the second type of accessory cells in the ovary in both invertebrates and vertebrates. They form a layer around the oocyte and nourish them with small molecules (no macromolecules, but eventually their smaller precursor molecules) by gap junctions.
Mammalian spermatogenesis is representative for most animals. In human males spermatogenesis begins at puberty in
seminiferous tubulesin the testes and go on continuously. Spermatogonia are immature germ cells. They proliferate continuously by mitotic divisions around the outer edge of the seminiferous tubules, next to the basal lamina. Some of these cells stop proliferation and differentiate into primary spermatocytes. After they proceed through the first meiotic division 2 secondary spermatocytes are produced. The 2 secondary spermatocytes undergo the second meiotic division to form 4 haploid spermatids. These spermatids differentiate morphologically into sperm by nuclear condensation, ejection of the cytoplasm and formation of the acrosomeand flagellum.The developing male germ cells do not complete cytokinesisduring spermatogenesis. Consequently cytoplasmic bridges assure connection between the clones of differentiating daughter cells to form a syncytium. In this way the haploid cells are supplied with all the products of a complete diploid genome. Sperm that carry a Y chromosome, for example, is supplied with essential molecules that are encoded by genes on the X chromosome.
Germ cell tumoris a rare cancer that can affect people at all ages. 2.4 children out of 1 million suffer the disease. This 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. [cite web
title=Germ cell tumors
publisher=CureSearch.org Medical Editorial Board
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