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STUDY QUESTION: Do advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) affect the cells of the human ovarian follicle? SUMMARY ANSWER: AGE accumulate on the surface of ovarian granulosa-lutein (GL) cells and monocytes by binding to RAGE and other receptors with possible functional effects on these cells. WHAT IS KNOWN ALREADY: AGE and RAGE are expressed in granulosa and theca cells, as well as in luteinized cells derived from the ovary. STUDY DESIGN, SIZE, DURATION: In this prospective cohort study, human follicle fluid-derived cells were isolated from aspirates of ovarian follicles of women who underwent assisted reproduction treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: GL cells and ovarian monocytes were found to contain AGE and RAGE and to bind AGE-bovine serum albumin (BSA) in correlation with the patients' chronological age. AGE-BSA and BSA failed to induce significantly the cleavage of caspase-3, phosphorylation of nuclear factor-κB or the binding of annexin V (the latter was marginally increased). AGE-fibronectin was found to induce detachment of cultured GL cells in vitro. LIMITATIONS, REASONS FOR CAUTION: The impact of AGE and RAGE in the ovary, shown here in cells in culture, remains to be affirmed in clinical settings. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the Norwegian Resource Centre for Women's Health, Oslo University Hospital. The authors have no conflicts of interests.
Stensen et al. (Tue,) studied this question.