Relationship of advanced glycation end products and their receptor to pelvic organ prolapse

The aims of this study are to detect levels of AGEs and RAGE and SNPs for RAGE in vaginal tissues of women with POP and rats in a repair location, and to explore the relationship between AGEs-RAGE pathway and POP.

This study involved human vaginal tissues in fornix from 44 women with POP and 46 women without POP who were assigned to pelvic floor reconstruction or LAVH. The proteins of AGEs, collagen I, and RAGE were detected by immunohistochemistry and Western blot with appropriate primary antibodies. The entire RAGE gene of 24 women with POP and 25 controls were sequenced, and SNPs within were detected. Then, sixty 8-week-old female Sprague-Dawley rats subjected to abdominal defect were divided into three surgical pelvic floor reconstruction repair groups (n=20/group): A, repair with non-absorable prolene mesh; B, repair with absorbable SIS mesh; and C, a no repair control group. 3, 9, 15, and 21 months after operation, rats were sacrificed and the expression of AGEs, RAGE and collagen I in the tissues of repair location were detected in the various experimental groups. Statistical analysis included comparison of means (Student's t-test) and proportions (Chi-square test or Fisher test).

By both immunohistochemistry and Western blot, patients with POP showed higher protein expression of AGEs of POP than controls (P<0.05). In contrast, the expression of collagen I was lower in POP patients than in the control group (P<0.05). No differences in the expression of RAGE between the POP patients and controls were observed (P>0.05). In POP patients, the expression of collagen I decreased particularly in patients≥60 years old (P<0.05), but there were no different in the expression of AGEs and RAGE dependent on age (P>0.05). RAGE gene sequence variance analysis identified 18 variable loci, but only two of these were potential SNPs: rs184003 (1806), rs55640627 (2346) (P<0.05). Both rs184003 and rs55640627 are both intronic variants, indicating that they may not influence the structure of RAGE. In rat surgical repair model, group B showed a greater extent of abdominal prolapse than groups A and C (P<0.05). Consistent with this, the expression of AGEs in group B was higher than groups A and C (P<0.05), and collagen I in group B was lower than the two others, further supporting our notion that AGEs are inversely related to type I collagen content.

In summary, this study demonstrates that AGEs and RAGE might play important roles in the physiopathology of POP. Further studies are required to explore mechanisms of how AGEs-RAGE pathway may contribute to tissue degeneration and fragility in POP.