Mechanisms of regulation of oocyte meiotic maturation

Published on June 30, 2019   37 min
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The aim of this lecture is to summarize the events associated with oocyte meiotic maturation, and review our core understanding of the signaling events involved in its regulation. My name is Marco Conti, and I'm currently at the faculty at the University of California, San Francisco.
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With this opening slide, I will highlight the components and morphology of the preovulatory ovarian follicle. Here, you can see a section of a mouse ovary with a preeminent antral follicle. A fully grown oocyte is surrounded by numerous layers of somatic cells. The somatic cells are epithelial granulosa cells that can be subdivided into mural granulosa cells lining the follicle wall, while cells surrounding the oocytes are called cumulus cells. Granulosa cells are separated from the surrounding stroma by a basal lamina and by layers of stroma cells called theca cells.
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An oocyte can be dissected out of the ovarian follicle, and under phase-contrast microscopy, appears as a large cell surrounded by a thick extracellular matrix called zona pellucida. In the cytoplasma of the oocyte, one can discern a prominent nucleolus and the nucleus called germinal vesical. This oocyte configuration corresponds to a quiescent state of the cell cycle term diakinesis state that can last even decades as in the human species. Only after puberty and after stimulation by circulating gonadotrophic hormones, the oocyte re-enters the meiotic cell cycle and progresses through what is called oocyte maturation. The cell cycle re-entry is marked by dissolution of the nuclear membrane, an event easily score under light microscopy and termed germinal vesical breakdown or GVBD. Condensation of the chromosomes and assembly of the meiotic spindle marks the oocyte progression to metaphase 1. These changes are best visualized by fixing and staining the oocyte. As you can see in the lower panel where microtubules of the spindles are in red, and chromosomes are in blue. Completion of this first meiotic division corresponds to an asymmetrical division and extrusion of a small polar body. This is followed by immediate re-entry into the second meiotic division and reassembly of the metaphase 2 spindle. At this stage, the oocyte, better called mature egg, is ready for fertilization. Only after fertilization by spermatozoa, it will complete the second division and extrude the second polar body. All these events related to the cell cycle are under the control of the M-phase promoting factor or MPF. MPF is a protein heteroduplex composed of a kinase CDK1 and its cyclin regulatory sub-unit. This protein complex functions as a master regulator of both the mitotic and meiotic cell cycle. During my presentation, you will see the mass of the regulation involved in the control of oocyte arrest and meiotic pre-entry converge onto the regulation of this critical molecular complex.
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Mechanisms of regulation of oocyte meiotic maturation

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