Matrix metalloproteinase-9 increases and Interleukin-10 reduces with increase in body mass index in polycystic ovary syndrome: A cross-sectional study


Background: Obesity, inflammation and alterations in matrix metalloproteinase-9 (MMP-9) and nitric oxide (NO) levels are involved in the development of polycystic ovary syndrome (PCOS).

Objective: To investigate the relationship of MMP-9, NO and interleukin-10 (IL-10) with the increase in body mass index (BMI) in women with PCOS.

Materials and Methods: Sixty two infertile PCOS women were included in the study. Serum levels of NO, IL-10 and MMP-9 were assessed in the women with increase in BMI.

Results: MMP-9 was significantly increased (p = 0.029) and IL-10 (p = 0.015) was significantly reduced in obese PCOS subjects compared to those with lesser BMI. MMP- 9 levels positively correlated with the duration of infertility (r = 0.253, p = 0.047) and negatively correlated with NO levels (r = - 0.259, p = 0.042). A significant negative correlation between the interleukin-10 levels and the BMI (r = - 0.272, p = 0.033) was also found in the PCOS subjects.

Conclusion: MMP-9 levels are increased in obese PCOS women and it is associated with NO levels and the duration of infertility.

Key words: Body mass index, Interleukin-10, Nitric oxide, Matrix metalloproteinase-9.

[1] Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004; 89: 2745–2749.

[2] Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. The Lancet 2007; 370: 685–697.

[3] Franks S. Polycystic ovary syndrome. Trends Endocrinol Metab 1989; 1: 60–63.

[4] Diamanti-Kandarakis E. Role of obesity and adiposity in polycystic ovary syndrome. Int J Obes 2007; 31 (Suppl.): S8–S13.

[5] Naderpoor N, Shorakae S, Joham A, Boyle J, De Courten B, Teede HJ. Obesity and polycystic ovary syndrome. Minerva Endocrinol 2015; 40: 37–51.

[6] Curry TE Jr, Osteen KG. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev 2003; 24: 428–465.

[7] Staun-Ram E, Goldman S, Gabarin D, Shalev E. Expression and importance of matrix metalloproteinase 2 and 9 (MMP- 2 and -9) in human trophoblast invasion. Reprod Biol Endocrinol 2004; 2: 59–71.

[8] Lewandowski KC, Komorowski J, O’Callaghan CJ, Tan BK, Chen J, Prelevic GM, et al. Increased circulating lLevels of matrix metalloproteinase-2 and -9 in women with the polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 1173–1177.

[9] Zullino S, Buzzella F, Simoncini T. Nitric oxide and the biology of pregnancy. Vascul Pharmacol 2018; 110: 71–74.

[10] Mahran A, Abdelmeged A, Shawki H, Moheyelden A, Ahmed AM. Nitric oxide donors improve the ovulation and pregnancy rates in anovulatory women with polycystic ovary syndrome treated with clomiphene citrate: A RCT. Int J Reprod Biomed 2016; 14: 9–14.

[11] Elkholi DGEY, Hammoudah SF. Subclinical inflammation in obese women with polycystic ovary syndrome. Middle East Fertility Society Journal 2012; 17: 195–202.

[12] Talaat RM, Mohamed YA, Mohamad EH, Elsharkawy M, Guirgis AA. Interleukin 10 (-1082 G/A) and (-819 C/T) gene polymorphisms in Egyptian women with polycystic ovary syndrome (PCOS). Meta Gene 2016; 9: 254–258.

[13] Spritzer PM, Lecke SB, Satler F, Morsch DM. Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome. Reproduction 2015; 149: R219–R227.

[14] Li L, Feng Q, Ye M, He Y, Yao A, Shi K. Metabolic effect of obesity on polycystic ovary syndrome in adolescents: a meta-analysis. J Obstet Gynaecol 2017; 37: 1036–1047.

[15] Baka S, Zourla K, Kouskouni E, Makrakis E, Demeridou S, Tzanakaki D, et al. Matrix metalloproteinases 2 and 9 and their tissue inhibitors in the follicular fluid of patients with polycystic ovaries undergoing in vitro fertilisation. In Vivo 2010; 24: 293–296.

[16] Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19: 41–47.

[17] Ojeda-Ojeda M, Murri M, Insenser M, Escobar-Morreale HF. Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS). Curr Pharm Des 2013; 19: 5775–5791.

[18] Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK, et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 2001; 103: 1410– 1415.

[19] Goldman S, Shalev E. MMPS and TIMPS in ovarian physiology and pathophysiology. Front Biosci 2004; 9: 2474–2483.

[20] Messinis IE, Messini CI, Anifandis G, Dafopoulos K. Polycystic ovaries and obesity. Best Pract Res Clin Obstet Gynaecol 2015; 29: 479–488.

[21] Nissi R, Talvensaari-Mattila A, Kotila V, Niinimäki M, Järvelä I, Turpeenniemi-Hujanen T. Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure. Reprod Biol Endocrinol 2013; 11: 2–7.

[22] Derosa G, Ferrari I, D’Angelo A, Tinelli C, Salvadeo SA, Ciccarelli L, et al. Matrix metalloproteinase-2 and -9 levels in obese patients. Endothelium 2008; 15: 219–224.

[23] Andrade VL, Petruceli E, Belo VA, Andrade-Fernandes CM, Caetano Russi CV, Bosco AA, et al. Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women. Clin Biochem 2012; 45: 412–415.

[24] Gomes VA, Vieira CS, Jacob-Ferreira AL, Belo VA, Soares GM, Fernandes JBF, et al. Imbalanced circulating matrix metalloproteinases in polycystic ovary syndrome. Mol Cell Biochem 2011; 353: 251–257.

[25] Gouge RC, Marshburn P, Gordon BE, Nunley W, Huet- Hudson YM. Nitric oxide as a regulator of embryonic development. Biol Reprod 1998; 58: 875–879.

[26] Sansbury BE, Hill BG. Regulation of obesity and insulin resistance by nitric oxide. Free Radic Biol Med 2014; 73: 383–399.

[27] Paradisi R, Fabbri R, Battaglia C, Facchinetti F, Venturoli S. Nitric oxide levels in women with missed and threatened abortion: results of a pilot study. Fertil Steril 2007; 88: 744– 748.

[28] Deligeoroglou E, Vrachnis N, Athanasopoulos N, Iliodromiti Z, Sifakis S, Iliodromiti S, et al. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol Endocrinol 2012; 28: 974–978.

[29] Heutling D, Schulz H, Nickel I, Kleinstein J, Kaltwasser P, Westphal S, et al. Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment. J Clin Endocrinol Metab 2008; 93: 82–90.

[30] Nehir Aytan A, Bastu E, Demiral I, Bulut H, Dogan M, Buyru F. Relationship between hyperandrogenism, obesity, inflammation and polycystic ovary syndrome. Gynecol Endocrinol 2016; 32: 709–713.

[31] Benson S, Janssen OE, Hahn S, Tan S, Dietz T, Mann K, et al. Obesity, depression, and chronic low-grade inflammation in women with polycystic ovary syndrome. Brain Behav Immun 2008; 22: 177–184.

[32] Leon-Cabrera S, Arana-Lechuga Y, Esqueda-León E, Terán-Pérez G, Gonzalez-Chavez A, Escobedo G, et al. Reduced systemic levels of IL-10 are associated with the severity of obstructive sleep apnea and insulin resistance in morbidly obese humans. Mediators Inflamm 2015; 2015: 493409–493418.

[33] Attie AD, Scherer PE. Adipocyte metabolism and obesity. J Lipid Res 2009; 50 (Suppl.): S395–S399.