The progressive decline of the ovarian follicle pool leads to reproductive ageing. The latter is accompanied by age-related disorders,\nincluding various types of cancer. In fact, the highest rates of ovarian cancer (OC) occur at postmenopause while OC risk is\nsignificantly modulated by parity records during previous fertile life. We approached the age-parity relationship in the C57BL/6\nmouse model and herein describe the presence of nonheme iron (hemosiderin) and deposits of the ââ?¬Å?age pigmentââ?¬Â lipofuscin in\nreproductively aged mouse ovaries by applying conventional histochemical methods and autofluorescence. In addition, the 8-\nOHdG adduct was evaluated in ovarian genomic DNA. Both hemosiderin and lipofuscin were significantly higher in virgin\ncompared to multiparous ovaries. The same pattern was observed for 8-OHdG. We conclude that nulliparity induces a longterm\naccumulation of iron and lipofuscin with concomitant oxidative damage to DNA in the mouse ovary. Since lipofuscin is a\nwidely accepted senescence marker and given the recently postulated role of lipofuscin-associated iron as a source of reactive\noxygen species (ROS) in senescent cells, these findings suggest a possible pathogenic mechanism by which nulliparity\ncontributes to an increased OC risk in the postmenopausal ovary.
Loading....