Abstract
Purpose
To assess the plasma levels of the inflammatory markers such as C-reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle.
Methods
Eighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles. Blood samples were collected at different time points: at the menstrual phase (days 2–3), periovulatory phase (days 12–13), and luteal phase (days 23–24). CRP and leptin concentrations were measured by enzyme immunoassay. GAGs were isolated using ion-exchange chromatography on DEAE-Sephacel and quantified as hexuronate. The structural characterization of chondroitin sulfate (CS) isomers was performed by fluorophore-assisted carbohydrate electrophoresis (FACE).
Results
In the women with ovulatory cycles, plasma GAG levels differed significantly during menstrual cycle, with increased values at the periovulatory with respect to the menstrual phase. No significant differences in CRP and leptin concentrations were observed through the menstrual cycle in both the examined cycles, but inter-group analysis revealed significant differences of CRP and leptin levels between the ovulatory and anovulatory cycles with higher values at periovulatory phase in the ovulatory cycles.
Conclusions
There are no fluctuations of both total GAG concentration and CS isomer content during menstrual cycle in the anovulatory cycles. A significant correlation between CRP and gonadotrophins was found. There is no significant difference in CRP across the menstrual cycle among ovulatory cycles, but there is a trend toward higher CRP at the periovulatory than the other phases, consistent with the significant difference in CRP between ovulatory and anovulatory cycles at the periovulatory phase. Both the trend and the significant result suggest an elevation in CRP with ovulation. These observations provide additional evidences to the hypothesis that the ovulation is an inflammatory-like phenomenon.
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References
Espey LL (1994) Current status of the hypothesis that mammalian ovulation is comparable to an inflammatory reaction. Biol Reprod 50:230–238
Brannstrom M, Enskog A (2002) Leukocyte networks and ovulation. J Reprod Immunol 57:47–60
Rae MT, Niven D, Critchley HO, Harlow CR, Hillier SG (2004) Antiinflammatory steroid action in human ovarian surface epithelial cells. J Clin Endocrinol Metab 89:4538–4544
Du Clos TW (2000) Function of C-reactive protein. Ann Med 32:274–278
Kluft C, Leuven JA, Helmerhorst FM, Krans HMJ (2002) Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormones replacement treatment. Vascul Pharmacol 39:149–154
Walsh BW, Paul S, Wild RA, Dean RA, Tracy RP, Cox DA, Anderson PW (2000) The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 85:214–218
Wander K, Brindle E, O’Connor KA (2008) C-reactive protein across the menstrual cycle. Am J Phys Anthropol 136:138–146
Maachi M, Piéroni L, Bruckert E, Jardel C, Fellahi S, Hainque B, Capeau J, Bastard JP (2004) Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord 28:993–997
Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC (1996) C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. Br Med J 312:1061–1065
Maruna P, Gurlich R, Frasko R, Haluzik M (2001) Serum leptin levels in septic men correlate well with C-reactive protein (CRP) and TNFα but not with BMI. Physiol Res 50:589–594
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432
Wunder DM, Yared M, Bersinger NA, Widmer D, Kretschmer R, Birkhäuser MH (2006) Serum leptin and C-reactive protein levels in the physiological spontaneous menstrual cycle in reproductive age women. Eur J Endocrinol 155:137–142
Roberts R, Gallagher J, Spooncer E, Allen TD, Bloomfield F, Dexter TM (1998) Heparan sulfate bound growth factors: a mechanism for stromal cell mediated haemopoiesis. Nature 332:376–378
Ramsden L, Rider CC (1992) Selective and differential binding of interleukin (IL)-a, IL-1 h, IL-2, and IL-6 to glycosaminoglycans. Eur J Immunol 22:3027–3031
Tanaka Y, Adams DH, Shaw S (1993) Proteoglycans on endothelial cells present adhesion-inducing cytokines to leukocytes. Immunol Today 14:111–115
Imanari T, Shinbo A, Ochiai H, Ikei T, Koshiishi I, Toyoda H (1992) Study on proteoglycans having low-sulfated chondroitin 4- sulfate in human urine and serum. J Pharmacobiodyn 15:231–237
De Muro P, Capobianco G, Formato M, Lepedda AJ, Cherchi GM, Gordini L, Dessole S (2009) Glycosaminoglycan and transforming growth factor b1 changes in human plasma and urine during the menstrual cycle, in vitro fertilization treatment, and pregnancy. Fertil Steril 92:320–327
Hensleigh PA, Fainstat T (1979) Corpus luteum dysfunction: serum progesterone levels in diagnosis and assessment of therapy for recurrent and threatened abortion. Fertil Steril 32:396–400
Bitter T, Muir HM (1962) Modified uronic acid carbazole reaction. Anal Biochem 4:330–334
Zinellu A, Pisanu S, Zinellu E, Lepedda AJ, Cherchi GM, Sotgia S, Carru C, Deiana L, Formato M (2007) A novel LIF-CE method for the separation of hyaluronan- and chondroitin sulfate-derived disaccharides: application to structural and quantitative analyses of human plasma low- and high-charged chondroitin sulfate isomers. Electrophoresis 28(14):2439–2447
Calabro A, Midura R, Wang A, West L, Plaas A, Hascall VC (2001) Fluorophore-assisted carbohydrate electrophoresis (FACE) of glycosaminoglycans. Osteoarthr Cartil 9:16–22
Karousou EG, Militsopoulou M, Porta G, De Luca G, Hascall VC, Passi A (2004) Polyacrylamide gel electrophoresis of fluorophore-labeled hyaluronan and chondroitin sulfate disaccharides: application to the analysis in cells and tissues. Electrophoresis 25:2919–2925
Koenig W, Lowel H, Baumert J, Meisinger C (2004) C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation 109:1349–1353
Considine RV, Sinka MK, Heiman ML, Krianciunas A, Bauer TL, Caro JF (1996) Serum immunoreactive leptin concentrations in normal weight and obese human. N Engl J Med 334:292–295
Li S (1994) Relationship between cellular DNA synthesis, PCNA expression and sex steroid hormone receptor status in the developing mouse ovary, uterus and oviduct. Histochemistry 102:405–413
Martin L, Finn CA, Trinder G (1973) Hypertrophy and hyperplasia in the mouse uterus after oestrogen treatment: an autoradiographic study. J Endocrinol 56:133–144
Pratt CW, Swaim MW, Pizzo SV (1989) Inflammatory cells degrade inter-alpha-inhibitor to liberate urinary proteinase inhibitors. J Leuk Biol 45:1–9
Zhuo L, Yoneda M, Zhao M, Yingsung W, Yoshida N, Kitagawa Y, Kawamura K, Suzuki T, Kimata K (2001) Defect in SHAP-hyaluronan complex causes severe female infertility. A study by inactivation of the bikunin gene in mice. J Biol Chem 276:7693–7696
Riad-Gabriel MG, Jinagouda SD, Sharma A, Boyadjian R, Saad MF (1998) Changes in plasma leptin during the menstrual cycle. Eur J Endocrinol 139:528–531
Messinis IE, Milingos S, Zikopoulos K, Kollios G, Seferiadis K, Lolis D (1998) Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone. Hum Reprod 13:1152–1156
Teirmaa T, Luukkaa V, Rouru J, Koulu M, Huupponen R (1998) Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal-weight women. Eur J Endocrinol 139:190–194
Lin KC (1999) Changes of circulating leptin levels during normal menstrual cycle: relationship to estradiol and progesterone. Kaohsiung J Med Sci 15:597–602
Hardie L, Trayhurn P, Abramovich D, Fowler P (1997) Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin Endocrinol 47:101–106
Ludwig M, Klein HH, Diedrich K, Ortmann O (2000) Serum leptin concentrations throughout the menstrual cycle. Arch Gynecol Obstet 263:99–101
O’Connor KA, Brindle E, Miller RC, Shofer JB, Ferrell RJ, Klein NA, Soules MR, Holman DJ, Mansfield PK, Wood JW (2006) Ovulation detection methods for urinary hormones: precision, daily and intermittent sampling and a combined hierarchical method. Hum Reprod 21:1442–1452
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Capobianco, G., de Muro, P., Cherchi, G.M. et al. Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles. Arch Gynecol Obstet 282, 207–213 (2010). https://doi.org/10.1007/s00404-010-1432-2
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DOI: https://doi.org/10.1007/s00404-010-1432-2