Influence of chemotherapeutic drugs on human granulosa cells

Cancer is one of the leading causes of death in persons aged 1 to 14 years and leukemias are the most common malignancies in childhood and are the primary cause of cancer-related mortality in the world. Chemotherapy is quite effective in treating cancers, but after successful treatment, young female cancer survivors face a potential threat of premature ovarian failure (POF) and infertility from gonadotoxicity of chemotherapeutic agent. Cytostatic drugs can target the oocyte directly, or can induce oocyte death indirectly via damage to surrounding granulosa cells, which play a key role in folliculogenesis and oocyte maturation. A more thorough understanding of the mechanism behind chemotherapy-induced infertility is necessary to develop new methods to preserve fertility in these patients. MicroRNAs (miRNAs) have recently begun to be explored in ovarian cells as small molecules with critical regulatory role. Importantly, the miRNAs profile in granulosa cells may possess high potential as a new marker for successful folliculogenesis and oocyte development. They can control steroidogenesis in cultured granulosa cells and are involved in control of proliferation, apoptosis and carcinogenesis. MicroRNA-21 (miR-21) and microRNA-132 (miR-132) are of the most abundant and highly expressed miRNAs in human oocytes and granulosa cells. miR-21 is an oncogenic miRNA and plays a critical role in maintaining the survival of granulosa cells in periovulatory follicles and acts as an antiapoptotic factor in granulosa cells. miR-132 has a key role in promotion of estradiol (E2) synthesis in murine ovarian granulosa cells. ... 4221 Zusammenfassungen in deutscher und englischer Sprache

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