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.
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References
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Capsule sRAGE could be a potential target in the pathophysiology of PCOS in human
BiJun Wang and MengMeng Hao contributed equally to this work.
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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
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DOI: https://doi.org/10.1007/s10815-016-0704-6