Advanced glycation end products and their receptor contribute to ovarian ageing

Do advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) affect the cells of the human ovarian follicle? AGE accumulate on the surface of ovarian granulosalutein (GL) cells and monocytes by binding to RAGE and other receptors with possible functional effects on these cells. AGE and RAGE are expressed in granulosa and theca cells, as well as in luteinized cells derived from the ovary. In this prospective cohort study, human follicle fluid-derived cells were isolated from aspirates of ovarian follicles of women who underwent assisted reproduction treatment. Immunofluorescence microscopy and multi-colour flow cytometry were used to determine the presence of AGE and RAGE on the surface of follicular fluid-derived cells and to characterize downstream effects of RAGE activation. GL cells and ovarian monocytes were found to contain AGE and RAGE and to bind AGEbovine serum albumin (BSA) in correlation with the patients chronological age. AGEBSA and BSA failed to induce significantly the cleavage of caspase-3, phosphorylation of nuclear factor-B or the binding of annexin V (the latter was marginally increased). AGE-fibronectin was found to induce detachment of cultured GL cells in vitro. The impact of AGE and RAGE in the ovary, shown here in cells in culture, remains to be affirmed in clinical settings. The ligands of RAGE and their effects in the ovary remain uncertain but this study implies that AGEs in the form of structural long-lived extracellular matrix proteins, rather than soluble AGEs, may play a role in the decline of ovarian function during ageing. The project was funded by the Norwegian Resource Centre for Womens Health, Oslo University Hospital. The authors have no conflicts of interests.