Skip to main content
Log in

MIF May Participate in Pathogenesis of Polycystic Ovary Syndrome in Rats through MAPK Signalling Pathway

  • Published:
Current Medical Science Aims and scope Submit manuscript

Abstract

The polycystic ovary syndrome (PCOS) model was established in rats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ovary was measured. The PCOS model in rats was established by dehydroepiandrosterone (DHEA). Thirty sexually immature female Sprague-Dawley rats were randomly and equally assigned to three groups: control group, PCOS group, and PCOS with high-fat diet (HFD) group. Serum hormones were assayed by radioimmunoassay (RIA). The ovaries were immunohistochemically stained with MIF, and the expression of MIF, p-JNK and p-p38 was detected by Western blotting in ovaries. The serum testosterone level, LH concentration, LH/FSH ratio, fasting insulin level and HOMA IR index in the PCOS group (6.077±0.478, 13.809±1.701, 1.820±0.404, 10.83±1.123 and 1.8692±0.1096) and PCOS with HFD group (6.075±0.439, 14.075±1.927, 1.779±0.277, 10.20±1.377 and 1.7736±0.6851) were significantly higher than those in the control group (4.949±0.337, 2.458±0.509, 1.239±0.038, 9.53±0.548 and 1.5329±0.7363), but there was no significant difference between the PCOS group and PCOS with HFD group. The expression levels of MIF, p-JNK, and p-p38 in the PCOS group (0.4048±0.013, 0.6233±0.093 and 0.7987±0.061) and PCOS with HFD group (0.1929±0.012, 0.3346±0.103 and 0.3468±0.031) were obviously higher than those in control group (0.2492±0.013, 0.3271±0.093 and 0.3393±0.061), but no significant difference was observed between PCOS group and PCOS with HFD group. It was suggested that MIF may participate in the pathogenesis of PCOS through the MAPK signalling pathway in PCOS rats induced by DHEA.

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.

Similar content being viewed by others

References

  1. Morrison MC, Kleemann R. Role of macrophage migration inhibitory factor in obesity, insulin resistance, type 2 diabetes, and associated hepatic comorbidities: a comprehensive review of human and rodent studies. Front Immunol, 2015,6:308

    Article  Google Scholar 

  2. Zabuliene L, Tutkuviene J. Body composition and polycystic ovary syndrome. Medicina (Kaunas, Lithuania), 2010,46(2):142

    Article  Google Scholar 

  3. Seli E, Duleba AJ. Optimizing ovulation induction in women with polycystic ovary syndrome. Curr Opin Obstet Gynecol, 2002,14(3):245–254

    Article  Google Scholar 

  4. González F, Kirwan J, Rote N, et al. Glucose and lipopolysaccharide regulate proatherogenic cytokine release from mononuclear cells in polycystic ovary syndrome. J Reprod Immunol, 2014,103(6):38–44

    Article  Google Scholar 

  5. Phelan N, O' Connor A, Tun TK, et al. Leucocytosis in women with polycystic ovary syndrome (PCOS) is incompletely explained by obesity and insulin resistance. Clin Endocrinol, 2012,78(1):107–113

    Article  Google Scholar 

  6. Hyejin L, Jee-Young O, Yeon-Ah S, et al. Is insulin resistance an intrinsic defect in asian polycystic ovary syndrome? Yonsei Med J, 2013,54(3):609–614

    Article  Google Scholar 

  7. Un Ju J, Myung-Sook C. Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease. Int J Mol Sci, 2014,15(4):6184–6223

    Article  Google Scholar 

  8. Bennett B, Bloom BR. Studies on the migration inhibitory factor associated with delayed-type hypersensivity: cytodynamics and specificity. Transplantation, 1967,5(4):Suppl:996–1000

    Article  Google Scholar 

  9. Javeed A, Zhao Y. Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection. Inflamm Res, 2008,57(2):45–50

    Article  CAS  Google Scholar 

  10. Hiroki M, Wataru I, Kazunori T, et al. Augmented reduction of islet β-cell mass in Goto-Kakizaki rats fed high-fat diet and its suppression by pitavastatin treatment. J Diabetes Investig, 2012,3(3):235–244

    Article  Google Scholar 

  11. Kleemann R, Kapurniotu A, Frank RW, et al. Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase. J Mol Biol, 1998,280(1):85–102

    Article  CAS  Google Scholar 

  12. Terrazas CA, Huitron E, Vazquez A, et al. MIF synergizes with Trypanosoma cruzi antigens to promote efficient dendritic cell maturation and IL-12 production via p38 MAPK. Int J Biol Sci, 2010,7(9):1298–1310

    Article  Google Scholar 

  13. Fan H, Hall P, Santos LL, et al. Macrophage migration inhibitory factor and CD74 regulate macrophage chemotactic responses via MAPK and Rho GTPase. J Immunol, 2011,186(8):4915–4924

    Article  CAS  Google Scholar 

  14. Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 2002,298(5600):1911–1912

    Article  CAS  Google Scholar 

  15. Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev, 2004,68(2):320–344

    Article  CAS  Google Scholar 

  16. Lai CF, Chaudhary L, Fausto A, et al. Erk is essential for growth, differentiation, integrin expression, and cell function in human osteoblastic cells. J Biol Chem, 2001,276(17):14 443–14 450

    Article  CAS  Google Scholar 

  17. Deschênes-Simard X, Kottakis F, Meloche S, et al. ERKs in cancer: friends or foes? Cancer Res, 2014,74(2):412–419

    Article  Google Scholar 

  18. Zeke A, Misheva M, Reményi A, et al. JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships. Microbiol Mol Biol Rev, 2016,80(3):793–835

    Article  CAS  Google Scholar 

  19. Wilmer WA, Dixon CL, Hebert C. Chronic exposure of human mesangial cells to high glucose environments activates the p38 MAPK pathway. Kidney Int, 2001,60(3):858–871

    Article  CAS  Google Scholar 

  20. Sumara G, Formentini I, Collins S, et al. Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell, 2009,136(2):235–248

    Article  CAS  Google Scholar 

  21. Lenarcik A, Bidzińska-Speichert B, Tworowska-Bardzińska U, et al. Hormonal abnormalities in firstdegree relatives of women with polycystic ovary syndrome (PCOS). Endokrynol Pol, 2011,62(2):129–133

    CAS  PubMed  Google Scholar 

  22. Rosenfield RL, Monica M, Kristen W, et al. Determination of the source of androgen excess in functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and a low-dose ACTH test. Hum Reprod, 2011,26(11):3138–3146

    Article  CAS  Google Scholar 

  23. Lee MT, Anderson E, Lee GY. Changes in ovarian morphology and serum hormones in the rat after treatment with dehydroepiandrosterone. Anat Rec, 1991,231(2):185–192

    Article  CAS  Google Scholar 

  24. Wang YX, Xie XM, Zhu WJ. Serum adiponectin and resistin levels in patients with polycystic ovarian syndrome and their clinical implications. J Huazhong Univ Sci Technol Med Sci, 2010,30(5):638–642

    Article  Google Scholar 

  25. Bach JP, Deuster O, BalzerGeldsetzer M, et al. The role of macrophage inhibitory factor in tumorigenesis and central nervous system tumors. Cancer, 2009,115(10):2031–2040

    Article  CAS  Google Scholar 

  26. Kleemann R, Bucala R, Kleemann R, et al. Macrophage migration inhibitory factor: critical role in obesity, insulin resistance, and associated comorbidities. Mediators Inflamm, 2010,84(1):111–116

    Google Scholar 

  27. Pedro GM, María Pilar M, José Alfredo M, et al. Differential Proinflammatory and Oxidative Stress Response and Vulnerability to Metabolic Syndrome in Habitual High-Fat Young Male Consumers Putatively Predisposed by Their Genetic Background. Int J Mol Sci, 2013,14(9):17 238–17 255

    Article  Google Scholar 

  28. Legro RSV, Daniel C, Kauffman RP. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Survey, 2004,59(2):141–154

    Article  Google Scholar 

  29. Ollila MM, Piltonen T, Puukka K, et al. Weight Gain and Dyslipidemia in Early Adulthood Associate with Polycystic Ovary Syndrome: Prospective Cohort Study. J Clin Endocrinol Metab, 2016,101(2):739–747

    Article  CAS  Google Scholar 

  30. Frank G, Rote NS, Judi M, et al. Elevated circulating levels of macrophage migration inhibitory factor in polycystic ovary syndrome. Cytokine, 2010, 51(3):240–244

    Article  Google Scholar 

  31. Jorly MM,Melchor ÁM, Eduardo RV, et al. Macrophage migration inhibitory factor in obese and non-obese women with polycystic ovary syndrome. Endocrinol Nutr, 2014,62(1):31–37

    Google Scholar 

  32. Vossler MR, Yao H, York RD, et al. cAMP activates MAP kinase and Elk-1 through a B-Raf-and Rap1-dependent pathway. Cell, 1997,89(1):73–82

    Article  CAS  Google Scholar 

  33. Nelson-Degrave VL, Wickenheisser JK, Hendricks KL, et al. Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome. Mol Endocrinol, 2005,19(2):379–390

    Article  CAS  Google Scholar 

  34. Lan CW, Chen MJ, Tai KY, et al. Functional microarray analysis of differentially expressed genes in granulosa cells from women with polycystic ovary syndrome related to MAPK/ERK signaling. Sci Rep, 2015,5:14 994

    Article  CAS  Google Scholar 

  35. Takahashi K, Koga K, Linge HM, et al. Macrophage CD74 contributes to MIF-induced pulmonary inflammation. Resp Res, 2009,10(1):1–14

    Article  Google Scholar 

  36. Lue H, Kapurniotu A, Fingerle-Rowson G, et al. Rapid and transient activation of the ERK MAPK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on JAB1/CSN5 and Src kinase activity. Cell Signal, 2006,18(5):688–703

    Article  CAS  Google Scholar 

  37. Zernecke A, Bernhagen J, Weber C. Macrophage migration inhibitory factor in cardiovascular disease. Circulation, 2008,117(12):1594–1602

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jing Yang or Hong Ye.

Additional information

This project was in part supported by the National Natural Science Foundation of China (No. 30973196).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, Dn., Li, Sj., Ding, Jl. et al. MIF May Participate in Pathogenesis of Polycystic Ovary Syndrome in Rats through MAPK Signalling Pathway. CURR MED SCI 38, 853–860 (2018). https://doi.org/10.1007/s11596-018-1953-7

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-018-1953-7

Key words

Navigation