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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 3 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
  1. Abbreviations: AGEs advanced glycation end Products, RAGE receptors for advanced glycation end products, ART Assisted Reproductive Technology, CML carboxymethyl lysine, E2 Estradiol, T testosterone, AMH anti-Mullerian hormone, AMHR-II AMH receptor, sRAGE soluble receptor for AGEs, IVF in vitro fertilization