Figure 2.

The top panels show the relationship between decreasing melatonin levels and the percent reduction in maximal fertility and the incidence of miscarriage as a function of age. At the time of menopause, total body melatonin levels have fallen to approximately half those in young, reproductively competent women. Among other functions, melatonin acts as a powerful direct radical scavenger and also indirectly reduces oxidative destruction by stimulating many antioxidative enzymes (see Figure 1). Considering the multiple protective actions of melatonin in limiting the accumulation of oxidatively damaged molecules during aging generally, it has often advanced as an anti-aging molecule. In the current report, we propose that the accumulated damage to key ovarian components due to the loss of this high-protective molecule contributes to infertility and reproductive cessation. The lower left panel summarizes some of the ovarian changes that have been reported when melatonin is not available in adequate amounts. Low levels of free radicals actually function as signalling molecules, but elevated levels mutilate DNA, proteins, lipids, etc. The majority of free radicals are produced in mitochondria; current evidence indicates that melatonin is synthesized in the mitochondria of ovarian cells so it is perfectly positioned to scavenge the continually produced reactants thereby providing protection against cellular dysfunction and infertility.