Volume 13, Issue 2 (2-2015)                   IJRM 2015, 13(2): 71-78 | Back to browse issues page

XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Shahnazi V, Zaree M, Nouri M, Mehrzad-Sadaghiani M, Fayezi S, Darabi M, et al . Influence of ω-3 fatty acid eicosapentaenoic acid on IGF-1 and COX-2 gene expression in granulosa cells of PCOS women. IJRM. 2015; 13 (2) :71-78
URL: http://journals.ssu.ac.ir/ijrmnew/article-1-622-en.html
1- Women’s Reproductive Health Research Center, Al-zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
2- Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3- Students Research Committee, Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4- Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz, Iran
5- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
6- Women’s Reproductive Health Research Center, Al-zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran , darabim@tbzmed.ac.ir
Abstract:   (907 Views)
Background: The omega-3 (ω-3) fatty acid eicosapentaenoic acid (EPA) is currently used in the clinic as a nutritional supplement to improve infertility, particularly in women with polycystic ovarian syndrome (PCOS).
Objective: The present study was designed to investigate the effect of EPA on insulin-like growth factor 1 (IGF-1) and cyclooxygenase 2 (COX-2) gene expression in primary cultured granulosa cells from patients undergoing in vitro fertilization (IVF), and also to compare this effect with those in granulosa cells of PCOS patients.
Materials and Methods: In this experimental study, human granulosa cells were isolated from follicular fluid of normal and PCOS women undergoing IVF by hyaluronidase digestions, followed by Percoll gradient centrifugation. Cells were cultured in vitro, exposed to a range of concentrations of the EPA (25-100 μM) for 24 hr, and investigated with respect to COX-2 and IGF-1 gene expression by real time-PCR.
Results: In both groups, all doses of the EPA significantly induced IGF-1 mRNAgene expression compared to the untreated control. High doses of EPA in thepresence of recombinant (r) FSH produced a stimulatory effect on IGF-1 and asuppressive effect (p=0.01) on the COX-2 gene expression, which were morepronounced in granulosa cells from PCOS patients.
Conclusion: EPA affect diversely the gene expression of IGF-1 and COX-2 in granulosa cells, which were more pronounced in PCOS compared to control. These findings represent the possible underlying molecular mechanisms for the positive impact of the ω-3 fatty acids on reproduction, especially in patients with PCOS.
Full-Text [PDF 232 kb]   (115 Downloads) |   |   Full-Text (HTML)  (107 Views)  
Type of Study: Original Article |

References
1. Kaur S, Archer KJ, Devi MG, Kriplani A, Strauss JF, Singh R. Differential gene expression in granulosa cells from polycystic ovary syndrome patients with and without insulin resistance: identification of susceptibility gene sets through network analysis. J Clin Endocrinol Metab 2012, 97: 2016-2021. [DOI:10.1210/jc.2011-3441]
2. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 2010, 8: 41-46. [DOI:10.1186/1741-7015-8-41]
3. Diamanti-Kandarakis E. Polycystic ovarian syndrome: pathophysiology, molecular aspects and clinical implications. Expert Rev Mol Med 2008, 10: 1-21. [DOI:10.1017/S1462399408000598]
4. Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, et al. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 1997; 91: 197-208. [DOI:10.1016/S0092-8674(00)80402-X]
5. Jakimiuk AJ, Weitsman SR, Navab A, Magoffin DA. Luteinizing hormone receptor, steroidogenesis acute regulatory protein, and steroidogenic enzyme messenger ribonucleic acids are overexpressed in thecal and granulosa cells from polycystic ovaries. J Clin Endocrinol Metab 2001, 86:1318-1323.
6. Sirois J, Sayasith K, Brown KA, Stock AE, Bouchard N, Doré M. Cyclooxygenase-2 and its role in ovulation: a 2004 account. Hum Reprod Update 2004; 10: 373-385. [DOI:10.1093/humupd/dmh032]
7. McNatty KP, Moore LG, Hudson NL, Quirke LD, Lawrence SB, Reader K, et al. The oocyte and its role in regulating ovulation rate: a new paradigm in reproductive biology. Reproduction 2004; 128: 379-386. [DOI:10.1530/rep.1.00280]
8. Howlett HC, Bailey CJ. A risk-benefit assessment of metformin in type 2 diabetes mellitus. Drug Saf 1999; 20: 489-503. [DOI:10.2165/00002018-199920060-00003]
9. Onagbesan O, Bruggeman V, Decuypere E. Intra-ovarian growth factors regulating ovarian function in avian species: A review. Anim Reprod Sci 2009; 111: 121-140. [DOI:10.1016/j.anireprosci.2008.09.017]
10. LaVoie HA, Garmey JC, Veldhuis JD. Mechanisms of insulin-like growth factor I augmentation of follicle-stimulating hormone-induced porcine steroidogenic acute regulatory protein gene promoter activity in granulosa cells. Endocrinology 1999, 140: 146-153. [DOI:10.1210/endo.140.1.6407]
11. Cao Z, Liu LZ, Dixon DA, Zheng JZ, Chandran B, Jiang BH. Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells. Cell Signal 2007; 19: 1542-1553. [DOI:10.1016/j.cellsig.2007.01.028]
12. Granado M, Martín AI, Villanúa MA, López-Calderón A. Experimental arthritis inhibits the insulin-like growth factor-I axis and induces muscle wasting through cyclooxygenase-2 activation. Am J Physiol Endocrinol Metab 2007; 292: 1656-1665. [DOI:10.1152/ajpendo.00502.2006]
13. Hurst S, Curtis CL, Rees SG, Harwood JL, Caterson B. Effects of n-3 polyunsaturated fatty acids on COX-2 and PGE2 protein levels in articular cartilage chondrocytes. Int J Exp Pathol 2004, 85: A22-A23. [DOI:10.1111/j.0959-9673.2004.369ab.x]
14. Fang XL, Shu G, Zhang ZQ, Wang SB, Zhu XT, Gao P, et al. Roles of α-linolenic acid on IGF-I secretion and GH/IGF system gene expression in porcine primary hepatocytes. Mol Biol Rep 2012; 39: 10987-10996. [DOI:10.1007/s11033-012-2000-6]
15. Seti H, Leikin-Frenkel A, Werner H. Effects of omega-3 and omega-6 fatty acids on IGF-I receptor signalling in colorectal cancer cells. Arch Physiol Biochem 2009; 115: 127-136. [DOI:10.1080/13813450902905899]
16. Fauser BCJM. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25. [DOI:10.1016/j.fertnstert.2003.10.004]
17. Sahmani M, Sakhinia E, Farzadi L, Najafipour R, Darabi M, Mehdizadeh A, et al. Two common polymorphisms in the peroxisome proliferator-activated receptor γ gene may improve fertilization in IVF. Reprod Biomed Online 2011; 23: 355-360. [DOI:10.1016/j.rbmo.2011.05.005]
18. Bódis J, Koppán M, Kornya L, Tinneberg HR, Török A. The effect of catecholamines, acetylcholine and histamine on progesterone release by human granulosa cells in a granulosa cell superfusion system. Gynecol Endocrinol 2002; 16: 259-264. [DOI:10.1080/gye.16.4.259.264]
19. Igoillo-Esteve M, Marselli L, Cunha DA, Ladrière L, Ortis F, Grieco FA, et al. Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes. Diabetologia 2010; 53: 1395-1405. [DOI:10.1007/s00125-010-1707-y]
20. Roelofs HM, Te Morsche RH, van Heumen BW, Nagengast FM, Peters WH. Over-expression of COX-2 mRNA in colorectal cancer. BMC Gastroenterol 2014; 14: 1. [DOI:10.1186/1471-230X-14-1]
21. Chen Y, Ke J, Long X, Meng Q, Deng M, Fang W, et al. Insulin-like growth factor-1 boosts the developing process of condylar hyperplasia by stimulating chondrocytes proliferation. Osteoarthr Cartil 2012; 20: 279-287. [DOI:10.1016/j.joca.2011.12.013]
22. Bafrani H, Saito H. Expression of c-Jun in human granulosa cells from patients participating in in vitro fertilization programs. Iran J Reprod Med 2008, 6: 488-504.
23. Green KH, Wong SCF, Weiler HA. The effect of dietary n-3 long-chain polyunsaturated fatty acids on femur mineral density and biomarkers of bone metabolism in healthy, diabetic and dietary-restricted growing rats. Prostaglandins Leukot Essent Fat Acids 2004; 71: 121-130. [DOI:10.1016/j.plefa.2004.03.001]
24. Nehra D, Le HD, Fallon EM, Carlson SJ, Woods D, White YA, et al. Prolonging the female reproductive lifespan and improving egg quality with dietary omega-3 fatty acids. Aging Cell 2012, 11:1046- 1054. [DOI:10.1111/acel.12006]
25. Sirotkin AV. Growth factors controlling ovarian functions. J Cell Physiol 2011; 226: 2222-2225. [DOI:10.1002/jcp.22588]
26. Velazquez MA, Zaraza J, Oropeza A, Webb R, Niemann H. The role of IGF1 in the in vivo production of bovine embryos from superovulated donors. Reproduction 2009; 137: 161-180. [DOI:10.1530/REP-08-0362]
27. Thill M, Becker S, Fischer D, Cordes T, Hornemann A, Diedrich K, et al. Expression of prostaglandin metabolising enzymes COX-2 and 15-PGDH and VDR in human granulosa cells. Anticancer Res 2009, 29: 3611-3618.
28. Jia Y, Lin J, Zeng W, Zhang C. Effect of prostaglandin on luteinizing hormone-stimulated proliferation of theca externa cells from chicken prehierarchical follicles. Prostaglandins Other Lipid Mediat 2010; 92: 77-84. [DOI:10.1016/j.prostaglandins.2010.03.005]
29. Lee CH, Lee, SD, Ou HC, Lai SC, Cheng YJ. Eicosapentaenoic Acid Protects against Palmitic Acid-Induced Endothelial Dysfunction via Activation of the AMPK/eNOS Pathway. Int J Mol Sci 2014; 15: 10334-10349. [DOI:10.3390/ijms150610334]
30. Glister C, Hatzirodos N, Hummitzsch K, Knight PG, Rodgers RJ. The global effect of follicle-stimulating hormone and tumour necrosis factor α on gene expression in cultured bovine ovarian granulosa cells. BMC Genom 2014; 15: 72-75. [DOI:10.1186/1471-2164-15-72]
31. Coffler MS, Patel K, Dahan MH, Malcom PJ, Kawashima T, Deutsch R, et al. Evidence for abnormal granulosa cell responsiveness to follicle-stimulating hormone in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 1742-1777. [DOI:10.1210/jc.2002-021280]
32. Yang M, Du J, Lu D, Ren C, Shen H, Qiao J, et al. Increased Expression of Kindlin 2 in Luteinized Granulosa Cells Correlates With Androgen Receptor Level in Patients With Polycystic Ovary Syndrome Having Hyperandrogenemia. Reprod Sci 2014, 21: 696-703. [DOI:10.1177/1933719113512536]

Send email to the article author


© 2020 All Rights Reserved | International Journal of Reproductive BioMedicine

Designed & Developed by : Yektaweb