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Helen M. Picton, Division of Reproduction and Early Development, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK,
Karen E. Hemmings, Division of Reproduction and Early Development, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
Oocyte metabolism reflects other aspects of the unique biology of this important cell type. The protracted process of mammalian oogenesis exacts a huge metabolic toll on the presumptive gamete. To ensure that the nutritional needs of oocytes are met oogenesis occurs in concert with folliculogenesis. Folliculogenesis is a lengthy process beginning with a primordial oocyte surrounded by a small number of flattened pregranulosa cells and ending with the ovulation of a fully grown, metaphase II oocyte, some weeks or months later. Throughout their development, oocytes and follicle cells are physically and metabolically linked via a complex network of homologous and heterologous gap junctions . Metabolic coupling of oocytes and somatic cells facilitates the transfer of molecules of <1kDa, including ions, amino acids, pyruvate and glucose, molecules such as adenosine triphosphate (ATP) , and other signaling molecules and meiosis-arresting signals from the somatic compartment of the follicle to the oocyte and vice versa to provide the physiological basis for oocyte and follicle development . While the metabolic cooperativity between oocytes and their companion granulosa cells is dynamic, discrete differences exist between the nutritional needs of oocytes and somatic granulosa cells and throughout their development oocytes are exposed to a changing nutritional environment as the follicular cells undergo proliferation, antral cavity formation, differentiation, and ovulation. In turn, oocytes have been shown to regulate apoptosis and cholesterol biosynthesis and metabolism by the follicular cells and so impact on follicular development .
In recent years, the improvement in the diagnosis, management and treatment of a range of solid and haematological childhood malignancies has led to a marked increase in the chances of long-term survival for a significant number of children and adolescents. However the chemo- and radiotherapies for treating cancers are frequently gonadotoxic and can render patients of either sex and any age temporarily or even permanently infertile. Like the malignant cells that are their intended targets, germ cells are highly susceptible to alkylating agents and platinum compounds used in chemotherapy formulations.
At the present time sperm banking remains the only proven method of fertility preservation for postpubertal boys, although hormonal manipulation and cryopreservation of testicular germ cells are possibilities for the future that could also benefit younger boys. The options for the preservation of female fertility are far more limited.
For girls and young women, mature oocyte freezing has many advantages, but it is unreliable. Most recently, the cryopreservation of immature oocytes in situ in small pieces of ovarian cortex followed by storage at low temperatures has been developed as an option to preserve female fertility before cancer treatment commences. Once the patient is in full remission and wishes to have fertility restored, the gonadal tissue can be thawed and either returned to the body as an autograft or, if there is any risk of reintroducing cancer cells in the graft, it may be possible to grow the gametes contained within the tissue to maturity in vitro.
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