Biomarkers of Ovarian Ageing

The ovary is the main regulator of female fertility, and its biologic clock is set to ensure reproductive success during a definite life stage. According to the evolutionary concept that organisms maximize fitness by promoting production of progeny, allocation of resources between reproductive and somatic functions is finely regulated during life [1]. Thus, it has been speculated that the premature ageing of the ovary when compared with somatic organs might result from increased energy demand for maintenance and repair processes in the soma compartment during ageing [1]. According to the human biologic clock, the gradual loss of female fertility becomes more dramatic in the late 30s with a steep decrease beginning after age 35, ending in menopause at mean age of 51 years [2]. This would preserve women from the physical stress of pregnancy in advanced age and maximize the length of time they can bear children [3]. As a result, increasing postponement of the first pregnancy represents a crucial factor in the widespread of subfertility in industrialized societies [4]. Given the intrapopulation variability of the reproductive life span [5], it is generally accepted that coping with this issue requires a careful reproductive counselling based on accurate predictive markers. Ovarian functional decline with ageing has been so far extensively characterized in terms of gradual depletion of ovarian follicles and reduced ability to produce oocytes competent for fertilization and further development [2]. The analysis of the molecular and cellular aspects of follicle ageing would require careful consideration. In fact, oocytes and granulosa cells of primordial follicles might remain in a 1