Advanced glycation end products and their receptor contribute to ovarian ageing.

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.