Follicular atresia is the breakdown of the ovarian follicles, which consist of an oocyte surrounded by granulosa cells and internal and external theca cells. It occurs continually throughout a person's (a person who has a typically presenting female reproductive system) life, as they are born with millions of follicles but will only ovulate around 400 times in their lifetime. Typically around 20 follicles mature each month but only a single follicle is ovulated; the follicle from which the oocyte was released becomes the corpus luteum. The rest undergo follicular atresia.
Atresia is a hormonally controlled apoptotic process that depends dominantly on granulosa cell apoptosis. Follicular atresia is inhibited by follicle-stimulating hormone (FSH), which promotes follicle development. Once the follicle has developed, it secretes estrogen, which in high levels decreases secretions of FSH. Granulosa cell apoptosis is considered the underlying mechanism of follicular atresia, and has been associated with five ligand-receptor systems involved in cell death: They are:
Granulosa cell apoptosis is promoted by tumor necrosis factor-alpha (TNFα), though the mechanism of TNFα is unclear.
Fas antigen, a cell surface receptor protein that is expressed on granulosa cells, mediates signals that induce apoptosis by binding Fas ligand and therefore plays an important role in follicular atresia. Lack of a functional Fas ligand / Fas receptor system has been linked to abnormal follicle development, and greater numbers of secondary follicles as a result of the inability to induce apoptosis.
TNF-related apoptosis-inducing ligand TRAIL activates Caspase 3 (CASP3), which in turn interacts with caspases 6, 7, 8, 9, and 10 to induce apoptosis in granulosa cells.
In addition, two intracellular inhibitor proteins, cellular FLICE-like inhibitory protein short form (cFLIPS) and long form (cFLIPL), which were strongly expressed in granulosa cells, may act as anti-apoptotic factors.
It has been proposed that enhanced levels of Nitrogen oxide in rats can prevent atresia of the ovarian follicle, and depressed levels have the opposite effect. .
There are 2 types of atresia:
- Obliterating: small follicles are invaded by fibroblast and macrophages;
- Cystic: in large follicles, a cavity remains.
Undergoing follicular atresia is necessary in order for people with typical female reproductive systems to maintain a healthy reproductive system. The inability to regulate granulosa cell apoptosis and undergo follicular atresia has been linked to the development of some hormone-related cancers and chemo-resistance.
2 types of atresia can be recognized: obliterating, in which small follicles are invaded by fibroblast and macrophages, and cystic, in which large follicles are involved and a cavity remains.
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