Ovarian Aging: Possible Molecular Mechanisms with Special Emphasis on DNA Repair Gene BRCA1

It has long been known that the female fertility decreases with increasing age and the normal process of reproductive aging varies considerably among women [1-3]. Female reproductive aging appears to be largely based on age related changes in ovarian function. Although quite a bit of information is available on the hormonal changes during ovarian aging, the molecular mechanisms behind the observed gradual decline of the follicle pool and the reduced oocyte quality are only being understood in the past few years. The fertility of mammalian females is dependent upon the synchronized development of follicles and oocytes, contained within them. The duration of the female fertile life span is influenced by the number of primordial follicles containing diplotene oocytes surrounded by one layer of cuboidal granulosa cells arrested in the first meiotic prophase stored in the ovary [4]. In particular, the progression of meiosis, wherein a germ cell-specific cell division decreases the number of chromosomes from diploid to haploid, must be arrested until just before ovulation. It has been known for several years that the somatic cells of follicles arrest the maturation of oocyte until both the follicle and the oocyte are fully developed. Eventually it will undergo ovulation and fertilization [5]. Follicular somatic cells are known to impose this arrest, which is required for co-ordinated oocyte–follicle development. The primordial follicle reserve decreases with increasing age, resulting in cessation of reproduction and menopause. A better understanding of oocyte biology is essential in this new generation of personalized medicine, as it can contribute to biomarker development, innovative therapeutic interventions, and new model to provide personalized treatments that are most likely to be efficient but with minimal toxicity.