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 development of mammalian oocytes
In mammals, thousands of oocytes are stored in the ovary. Stored oocytes are relatively small and have to increase their volume by a factor of 50 to contain enough storage material for the development of the embryo after fertilization (Eppig and O'Brien, 1996; Peters, 1969). Oocytes can reach their enormous size, because they are surrounded by special somatic cells that feed them with precursors of macromolecules through gap junctions. The functional unit of oocyte and somatic cells is termed follicle.
In their storage state, oocytes are surrounded by a single epithelial layer of flat somatic cells in a so-called primordial follicle (Figure, 1. Primordial Follicle). Periodically, some primordial follicles start to grow. The somatic cells become cuboidal and divide, and are now referred to as granulosa cells. Concurrently, the oocyte grows. It accumulates storage proteins and mRNAs (Chesnel and Eppig, 1995; Eppig, 1991) and reorganizes the configuration of its chromatin and cytoskeleton (Mattson and Albertini, 1990). Also the epigenetic modifications that are essential for the development of the embryo after fertilization are established (Kono et al., 1996). Thereby, the oocyte progressively gains the ability to mature into an egg that can give rise to an embryo after fertilization (Sorensen and Wassarman, 1976). In parallel, small cavities form between the granulosa cells that finally fuse into a large cavity termed antrum. The antrum is filled with proteins, hormones and other molecules, and divides the granulosa cells into two groups: the cumulus cells that are in close proximity of the oocyte, and the mural granulosa cells in the periphery (Figure, 4. Antral Follicle).
Once every menstrual cycle, the pituitary secretes follicle stimulating hormone (FSH), a gonadotropin which causes several of the antral follicles to develop into fully grown Graafian follicles that have a diameter of about 600 μm and consist of about 60 000 granulosa cells. The oocyte is now fully developed and has a diameter of about 75 μm (Mehlmann, 2005; Wassarman, 2002). The human Graafian follicle is even larger. It has a diameter of approximately 2 cm and contains an oocyte with a diameter of 100 μm (McGee and Hsueh, 2000; Mehlmann, 2005). The development from primordial to Graafian follicle takes more than two months in rodents and more than a year in humans (McGee and Hsueh, 2000).
 regulation and stages of meiotic maturation
Granulosa cells do not only support oocyte growth, but they also control oocyte development. Throughout follicle growth, oocytes are arrested in prophase. Prophase arrest depends on signaling from the granulosa cells, because oocytes that are isolated from antral follicles spontaneously mature into eggs (Mehlmann, 2005). The pathways that maintain the oocyte arrested in prophase are mostly unknown. However, it is well established that prophase arrest depends on high cAMP levels in the oocyte, because spontaneous maturation of isolated oocytes can be prevented if the culture medium is supplemented with cAMP phosphodiesterase inhibitors or cAMP analogs such as dibutyryl-cAMP (dbcAMP) (Conti et al., 2002; Mehlmann, 2005).
But how is maturation of an oocyte triggered in vivo? At the middle of the menstrual cycle, a surge of luteinizing hormone (LH) from the pituitary induces that the oocyte matures into an egg. The exact pathways that induce meiotic maturation are not yet understood, but binding of LH to receptors on the outermost mural granulosa cells is known to decrease the cAMP levels in the oocyte (Mehlmann, 2005). Still in the follicle, the oocyte thereupon starts to mature into an egg.
During maturation, the entire oocyte is remodeled. This process in only poorly understood in humans, but it has been partially characterized in mouse. In a fully grown mouse oocyte, the nucleus resides in the center (Figure) (Brunet and Maro, 2007). The chromosomes are condensed around the nucleolus and clustered in proximity of the nuclear envelope (Mattson and Albertini, 1990). The homologous chromosomes are connected with each other through recombination between their chromosome arms that is established during early prophase arrest. Thereby, they form a unit that is referred to as bivalent (Kudo et al., 2006; Petronczki et al., 2003). Like in many other species (Manandhar et al., 2005), mouse oocytes do not have centrosomes, but they have distinct acentriolar MTOCs that contain the pericentriolar material components gamma-tubulin (Gueth-Hallonet et al., 1993; Palacios et al., 1993) and pericentrin (Carabatsos et al., 2000). When the cAMP levels in the oocyte decrease due to the LH surge, the nucleus breaks down, and an acentrosomal spindle assembles in the center of the oocyte around the bivalent chromosomes . Spindle assembly takes about four hours, and is thus much slower than in mitotic cells (Brunet and Maro, 2005; Dumont et al. 2007; Schuh and Ellenberg 2007). The spindle then relocates for 2-3 hours to the cortex of the oocyte by an actin dependent mechanism (Azoury et al., 2008; Li et al., 2008; Longo and Chen, 1985; Schuh and Ellenberg, 2008; Sun and Schatten, 2006; Verlhac et al., 2000, ). At the cortex, the homologous chromosomes separate, and half of them are extruded in a small cell termed polar body. The remaining chromosomes become aligned in the metaphase II spindle, and the egg stays arrested in this stage until it is fertilized.
While the oocyte matures, which takes 12-14 hours, a sticky mucified matrix develops between the cumulus cells that surround the oocyte in the follicle. The matrix strongly expands the cumulus cell layers and thereby ruptures the surface of the follicle so that the egg can be released into the oviduct (Yokoo and Sato, 2004).
After fertilization, the egg extrudes a second polar body to eliminate half of the sister chromatids of the remaining chromosomes. Male and female pronuclei form and fuse, and the mitotic divisions of the embryo begin.
The remains of the follicle have important functions for the development of the embryo. They form the corpus luteum that produces steroid hormones for establishing and maintaining a pregnancy (Eppig, 2001). If an egg is not fertilized the corpus luteum degenerates.
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