Table 2 Studies evaluating the association between AGEs and PCOS
From: Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS
Study | Subjects, animals, or cell line | Intervention | Outcome |
|---|---|---|---|
Diamanti- Kandarakis et al., 2007 [76] | - Female Wistar rats fed high (H-AGE) or low (L-AGE) diet for 6 months | - AGEs’ levels in ovarian theca cells - RAGE expression - Plasma T level | In H-AGE diet rats: - Elevated AGEs’ deposition in ovarian theca interna cells - Increased RAGE staining in granulosa cells - Higher plasma T levels |
Chatzigeorgiou A et al., 2013 [78] | - Female Wistar rats fed high (H-AGE) or low (L-AGE) diet for 3Â months | - Plasma T, E2 and P4 levels - Expression of scavenger receptors for AGEs | In H-AGE diet rats: - High T plasma levels - Lower levels of E2 and P4 - Reduced expression of scavenger receptors for AGEs |
Jinno et al., 2011 [73] | - Women with (n = 71) and without (n = 86) PCOS undergoing ART | - Measurement of toxic AGEs (TAGE), pentosidine, and CML in blood and follicular fluid | - Negative correlation between E2 and follicular fluid AGEs (TAGE, Pentosidine and CML) - Negative correlation between E2 and serum AGEs (TAGE) |
Diamanti- Kandarakis et al., 2005 [27] | - Women with (n = 29) or without (n = 22) PCOS | - Serum AGEs’ levels and RAGE expression in circulating monocytes - Correlation between AGEs and T levels | - Higher serum AGEs’ levels and elevated expression of RAGE in PCOS - Positive correlation between serum AGEs and T |
Tantalaki et al., 2014 [77] | - Women with PCOS (n = 23) were given isocaloric diet containing high (H-AGE) or low (L-AGE) levels of AGEs for 2 months | - Serum AGEs and androgens (T, and androstendione) levels, free androgen index | Women with PCOS on H-AGE diet: - Higher serum AGEs - Elevated T, androstenedione, and free androgen index |
Diamanti-Kandarakis et al., 2013 [80] | - Human ovarian granulosa cell line (KGN) treated with recombinant LH in the presence or absence of human glycated albumin (HGA) (representative of AGEs) | - Effect of AGE-RAGE on LH signaling | - Interference of LH actions by ovarian AGEs due to sustained activation of ERK1/2 and MAPK signaling - May also impair follicular responses to hormones |
Merhi et al., 2015 [83] | - Cumulus granulosa cells (CCs) (n = 6) treated with HGA (representative of AGEs) obtained from women who underwent IVF - KGN granulosa cell line treated with recombinant AMH (rAMH) in the presence or absence of HGA - Follicular fluid levels of sRAGE and AGEs in women undergoing IVF | - mRNA expression of LH receptor (LHR), AMH, AMHR-II, and RAGE by RT-PCR - RAGE protein expression by immunofluorescence - Immunofluorescence for SMAD 1/5/8 phosphorylation (AMH signaling pathway) - Correlation between sRAGE and AGEs (pentosidine and CML) in follicular fluid | - HGA increased LHR and AMHR-II mRNA levels - HGA did not change AMH mRNA levels - HGA increased RAGE protein levels - HGA significantly increased rAMH-induced SMAD 1/5/8 phosphorylation - sRAGE positively correlated with pentosidine and CML |