Skip to main content

Advertisement

Log in

Follicular fluid soluble receptor for advanced glycation endproducts (sRAGE): a potential protective role in polycystic ovary syndrome

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To explore the relationships between the soluble receptor for advanced glycation endproducts (sRAGE) and the outcome parameters following in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) and investigate the protective effect of sRAGE in PCOS development regarding inflammation.

Methods

We conducted a prospective analysis of a subsample of 74 participants from the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University. We quantified sRAGE, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-α), interleukelin-6 (IL-6), and C-reactive protein (CPR) protein levels in the follicular fluid from 39 PCOS and 35 non-PCOS reproductive-age women. sRAGE and VEGF, TNF-α, IL-6, and CRP in follicular fluid aspirated without blood were measured by ELISA.

Results

sRAGE concentrations in the follicular fluid were significantly lower in the PCOS group compared to those in the control group, while VEGF, TNF-α, IL-6, and CRP concentrations were significantly higher in the PCOS group than in the control group (P < 0.05). sRAGE was significantly, inversely correlated with the total dose of gonadotropin (Gn) in the PCOS group undergoing IVF treatment (r = −0.451, P = 0.004). After adjusting for age and Gn dose (in international units used per cycle), sRAGE protein levels in the follicular fluid were significantly, inversely related to VEGF (r = −0.378, P = 0.018), TNF-α (r = −0.450, P = 0.004), IL-6 (r = −0.455, P = 0.004), and CRP (r = −0.375, P = 0.019).

Conclusion

sRAGE in the follicular fluid might exert a protective effect against the inflammatory action of PCOS development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hart R, Doherty DA. The potential implications of a PCOS diagnosis on a woman’s long-term health using data linkage. J Clin Endocrinol Metab. 2015;100(3):911–9. doi:10.1210/jc.2014-3886.

    Article  CAS  PubMed  Google Scholar 

  2. Liu M, Gao J, Zhang Y, Li P, Wang H, Ren X, et al. Serum levels of TSP-1, NF-kappaB and TGF-beta1 in polycystic ovarian syndrome (PCOS) patients in northern China suggest PCOS is associated with chronic inflammation. Clin Endocrinol. 2015;83(6):913–22. doi:10.1111/cen.12951.

    Article  CAS  Google Scholar 

  3. Pertynska-Marczewska M, Diamanti-Kandarakis E, Zhang J, Merhi Z. Advanced glycation end products: a link between metabolic and endothelial dysfunction in polycystic ovary syndrome? Metab Clin Exp. 2015;64(11):1564–73. doi:10.1016/j.metabol.2015.08.010.

    Article  CAS  PubMed  Google Scholar 

  4. Hu H, Jiang H, Ren H, Hu X, Wang X, Han C. AGEs and chronic subclinical inflammation in diabetes: disorders of immune system. Diabetes Metab Res Rev. 2015;31(2):127–37. doi:10.1002/dmrr.2560.

    Article  PubMed  Google Scholar 

  5. Palimeri S, Palioura E, Diamanti-Kandarakis E. Current perspectives on the health risks associated with the consumption of advanced glycation end products: recommendations for dietary management. Diabetes, Metab Syndr Obes: Targets Ther. 2015;8:415–26. doi:10.2147/dmso.s63089.

    Google Scholar 

  6. Wang YS, Li YY, Wang LH, Kang Y, Zhang J, Liu ZQ, et al. Tanshinone IIA attenuates chronic pancreatitis-induced pain in rats via downregulation of HMGB1 and TRL4 expression in the spinal cord. Pain Physician. 2015;18(4):E615–28.

    PubMed  Google Scholar 

  7. Lazo M, Halushka MK, Shen L, Maruthur N, Rebholz CM, Rawlings AM, et al. Soluble receptor for advanced glycation end products and the risk for incident heart failure: the atherosclerosis risk in communities study. Am Heart J. 2015;170(5):961–7. doi:10.1016/j.ahj.2015.08.008.

    Article  CAS  PubMed  Google Scholar 

  8. Merhi Z. Advanced glycation end products and their relevance in female reproduction. Human reproduction (Oxford, England). 2014; 29(1): 135–45. doi:10.1093/humrep/det383.

  9. Romero R, Espinoza J, Hassan S, Gotsch F, Kusanovic JP, Avila C, et al. Soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) in amniotic fluid: modulation by infection and inflammation. J Perinat Med. 2008;36(5):388–98. doi:10.1515/jpm.2008.076.

    Article  CAS  PubMed  Google Scholar 

  10. Rzepka R, Dolegowska B, Rajewska A, Kwiatkowski S, Salata D, Budkowska M, et al. Soluble and endogenous secretory receptors for advanced glycation end products in threatened preterm labor and preterm premature rupture of fetal membranes. BioMed Res Int. 2015;2015:568042. doi:10.1155/2015/568042.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Merhi Z, Irani M, Doswell AD, Ambroggio J. Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve. J Clin Endocrinol Metab. 2014;99(2):E226–33. doi:10.1210/jc.2013-3839.

    Article  CAS  PubMed  Google Scholar 

  12. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human reproduction (Oxford, England). 2004; 19(1): 41–7.

  13. Wu TL, Tsai CC, Wang YY, Ho KY, Wu YM, Hung HC, et al. The association between the RAGE G82S polymorphism, sRAGE and chronic periodontitis in Taiwanese individuals with and without diabetes. J Periodontal Res. 2015;50(6):881–9. doi:10.1111/jre.12282.

    Article  CAS  PubMed  Google Scholar 

  14. Sharma I, Dhawan V, Saha SC, Rashmi B, Dhaliwal LK. Implication of the RAGE-EN-RAGE axis in endometriosis. Int J Gynaecol Obstet: Off Organ Int Fed Gynaecol Obstet. 2010;110(3):199–202. doi:10.1016/j.ijgo.2010.03.037.

    Article  CAS  Google Scholar 

  15. Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front biosci (Elite edition). 2010;2:1184–95.

    Article  Google Scholar 

  16. Lee EJ, Park EY, Mun H, Chang E, Ko JY, do Kim Y, et al. Soluble receptor for advanced glycation end products inhibits disease progression in autosomal dominant polycystic kidney disease by down-regulating cell proliferation. FASEB J: Off Publ Fed Am Soc Exp Biol. 2015;29(8):3506–14. doi:10.1096/fj.15-272302.

    Article  CAS  Google Scholar 

  17. He CT, Lee CH, Hsieh CH, Hsiao FC. Soluble form of receptor for advanced glycation end products is associated with obesity and metabolic syndrome in adolescents. Int J Endocrinol. 2014;2014:657607. doi:10.1155/2014/657607.

    PubMed  PubMed Central  Google Scholar 

  18. Gonzalez F. Nutrient-induced inflammation in polycystic ovary syndrome: role in the development of metabolic aberration and ovarian dysfunction. Semin Reprod Med. 2015;33(4):276–86. doi:10.1055/s-0035-1554918.

    Article  CAS  PubMed  Google Scholar 

  19. Peluso C, Fonseca FL, Rodart IF, Cavalcanti V, Gastaldo G, Christofolini DM, et al. AMH: an ovarian reserve biomarker in assisted reproduction. Clin Chim Acta: Int J Clin Chem. 2014;437:175–82. doi:10.1016/j.cca.2014.07.029.

    Article  CAS  Google Scholar 

  20. Irani M, Merhi Z. Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertil Steril. 2014;102(2):460–8.e3. doi:10.1016/j.fertnstert.2014.04.046.

    Article  CAS  PubMed  Google Scholar 

  21. Bonetti TC, Borges Jr E, Braga DP, Iaconelli Jr A, Kleine JP, Silva ID. Intrafollicular soluble receptor for advanced glycation end products (sRAGE) and embryo quality in assisted reproduction. Reprod Biomed Online. 2013;26(1):62–7. doi:10.1016/j.rbmo.2012.10.001.

    Article  CAS  PubMed  Google Scholar 

  22. Guclu M, Ali A, Eroglu DU, Buyukuysal SO, Cander S, Ocak N. Serum levels of sRAGE are associated with body measurements, but not glycemic parameters in patients with prediabetes. Metab Syndr Relat Disord. 2016;14(1):33–9. doi:10.1089/met.2015.0078.

    Article  CAS  PubMed  Google Scholar 

  23. Uribarri J, del Castillo MD, de la Maza MP, Filip R, Gugliucci A, Luevano-Contreras C et al. Dietary advanced glycation end products and their role in health and disease. 2015.

  24. Schmidt AM. Soluble RAGEs—prospects for treating & tracking metabolic and inflammatory disease. Vasc Pharmacol. 2015;72:1–8. doi:10.1016/j.vph.2015.06.011.

    Article  CAS  Google Scholar 

  25. Stewart C, Cha S, Caudle RM, Berg K, Katz J. Decreased levels of soluble receptor for advanced glycation end products in patients with primary Sjogren’s syndrome. Rheumatol Int. 2008;28(8):771–6. doi:10.1007/s00296-008-0529-4.

    Article  CAS  PubMed  Google Scholar 

  26. Chen CG, Tang P, Yu ZT. Effect of HMGB1 on the VEGF-C expression and proliferation of esophageal squamous cancer cells. Zhonghua zhong liu za zhi Chin J Oncol. 2012;34(8):566–70. doi:10.3760/cma.j.issn.0253-3766.2012.08.002.

    CAS  Google Scholar 

  27. Goova MT, Li J, Kislinger T, Qu W, Lu Y, Bucciarelli LG, et al. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol. 2001;159(2):513–25. doi:10.1016/s0002-9440(10)61723-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tal R, Seifer DB, Grazi RV, Malter HE. Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation. Reprod Biol Endocrinol: RB&E. 2014;12:82. doi:10.1186/1477-7827-12-82.

    Article  Google Scholar 

  29. Manau D, Balasch J, Jimenez W, Fabregues F, Civico S, Casamitjana R, et al. Follicular fluid concentrations of adrenomedullin, vascular endothelial growth factor and nitric oxide in IVF cycles: relationship to ovarian response. Hum Reprod (Oxford, England). 2000;15(6):1295–9.

    Article  CAS  Google Scholar 

  30. Wu R, Van der Hoek KH, Ryan NK, Norman RJ, Robker RL. Macrophage contributions to ovarian function. Hum Reprod Update. 2004;10(2):119–33. doi:10.1093/humupd/dmh011.

    Article  PubMed  Google Scholar 

  31. Gonzalez F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012;77(4):300–5. doi:10.1016/j.steroids.2011.12.003.

    Article  CAS  PubMed  Google Scholar 

  32. Escobar-Morreale HF, Luque-Ramirez M, Gonzalez F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril. 2011;95(3):1048–58.e1-2. doi:10.1016/j.fertnstert.2010.11.036.

    Article  CAS  PubMed  Google Scholar 

  33. Cataldegirmen G, Zeng S, Feirt N, Ippagunta N, Dun H, Qu W, et al. RAGE limits regeneration after massive liver injury by coordinated suppression of TNF-alpha and NF-kappaB. J Exp Med. 2005;201(3):473–84. doi:10.1084/jem.20040934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Malickova K, Jarosova R, Rezabek K, Fait T, Masata J, Janatkova I, et al. Concentrations of sRAGE in serum and follicular fluid in assisted reproductive cycles—a preliminary study. Clin Lab. 2010;56(9–10):377–84.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grant 81571409 from the National Natural Science Foundation, The mechanism of sRAGE in the regulation of VEGF production in granulosa cells of PCOS.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to YiHong Guo.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Additional information

Capsule sRAGE could be a potential target in the pathophysiology of PCOS in human

BiJun Wang and MengMeng Hao contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, B., Hao, M., Yang, Q. et al. Follicular fluid soluble receptor for advanced glycation endproducts (sRAGE): a potential protective role in polycystic ovary syndrome. J Assist Reprod Genet 33, 959–965 (2016). https://doi.org/10.1007/s10815-016-0704-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-016-0704-6

Keywords

Navigation