Abstract
Objective
To compare the peritoneal fluid (PF) proteome of women with and without uterine leiomyomas.
Study design
PF samples were collected at laparoscopy from 14 women with uterine leiomyomas and 14 patients without leiomyomas who underwent tubal sterilization. PF samples were subjected to two-dimensional gel electrophoresis, silver stained, digitally captured, and compared by computerised analysis. Protein spots with aberrant expression in PF of women with leiomyomas were identified by liquid chromatography tandem mass spectrometry.
Results
One isoform of leucine-rich alpha-2-glycoprotein (LRGm), one immunoglobulin light chain, and one unidentified protein (pI: 5.62; M r: 51.1 kDa) had significantly higher expression in PF of women with leiomyomas. Two isoforms of fibrinogen gamma chain had decreased expression in PF of women with uterine leiomyomas. Following Bonferroni correction for multiple comparisons, the aberrant expressions of LRGm and of one isoform of fibrinogen gamma chain was confirmed. The expression of these molecules was not affected by the phase of the menstrual cycle.
Conclusions
Uterine leiomyomas are associated with changes in proteins present within the peritoneal fluid. The physiopathological relevance of the increased expression of LRGm in PF of women with uterine leiomyomas remains unclear.
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References
Ahn WS, Kim KW, Bae SM, Yoon JH, Lee JM, Namkoong SE et al (2003) Targeted cellular process profiling approach for uterine leiomyoma using cDNA microarray, proteomics and gene ontology analysis. Int J Exp Pathol 84:267–279. doi:10.1111/j.0959-9673.2003.00362.x
Arici A, Sozen I (2000) Transforming growth factor-beta3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Fertil Steril 73:1006–1011. doi:10.1016/S0015-0282(00)00418-0
Bini L, Magi B, Marzocchi B, Cellesi C, Berti B, Raggiaschi R et al (1996) Two-dimensional electrophoretic patterns of acute-phase human serum proteins in the course of bacterial and viral diseases. Electrophoresis 17:612–616. doi:10.1002/elps.1150170333
Chegini N, Tang XM, Ma C (1999) Regulation of transforming growth factor-beta1 expression by granulocyte macrophage-colony-stimulating factor in leiomyoma and myometrial smooth muscle cells. J Clin Endocrinol Metab 84:4138–4143. doi:10.1210/jc.84.11.4138
Chegini N, Verala J, Luo X, Xu J, Williams RS (2003) Gene expression profile of leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy. J Soc Gynecol Investig 10:161–171. doi:10.1016/S1071-5576(03)00004-2
Chegini N, Luo X, Ding L, Ripley D (2003) The expression of Smads and transforming growth factor beta receptors in leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy. Mol Cell Endocrinol 209:9–16. doi:10.1016/j.mce.2003.08.007
Dou Q, Zhao Y, Tarnuzzer RW, Rong H, Williams RS, Schultz GS et al (1996) Suppression of transforming growth factor-beta (TGF beta) and TGF beta receptor messenger ribonucleic acid and protein expression in leiomyomata in women receiving gonadotropin-releasing hormone agonist therapy. J Clin Endocrinol Metab 81:3222–3230. doi:10.1210/jc.81.9.3222
Englund K, Lindblom B, Carlstrom K, Gustavsson I, Sjoblom P, Blanck A (2000) Gene expression and tissue concentrations of IGF-I in human myometrium and fibroids under different hormonal conditions. Mol Hum Reprod 6:915–920. doi:10.1093/molehr/6.10.915
Ferrero S, Gillott DJ, Anserini P, Remorgida V, Price KM, Ragni N et al (2005) Vitamin D binding protein in endometriosis. J Soc Gynecol Investig 12:272–277. doi:10.1016/j.jsgi.2005.01.027
Ferrero S, Gillott DJ, Remorgida V, Anserini P, Price K, Ragni N et al (2005) Haptoglobin beta chain isoforms in the plasma and peritoneal fluid of women with endometriosis. Fertil Steril 83:1536–1543. doi:10.1016/j.fertnstert.2004.11.064
Ferrero S, Abbamonte LH, Giordano M, Parisi M, Ragni N, Remorgida V (2006) Uterine myomas, dyspareunia, and sexual function. Fertil Steril 86:1504–1510. doi:10.1016/j.fertnstert.2006.04.025
Ferrero S, Gillott DJ, Remorgida V, Anserini P, Leung KY, Ragni N, Grudzinskas JG (2007) Proteomic analysis of peritoneal fluid in women with endometriosis. J Proteome Res 6:3402–3411. doi:10.1021/pr060680q
Hoffman PJ, Milliken DB, Gregg LC, Davis RR, Gregg JP (2004) Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis. Fertil Steril 82:639–649. doi:10.1016/j.fertnstert.2004.01.047
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685. doi:10.1038/227680a0
Lee BS, Nowak RA (2001) Human leiomyoma smooth muscle cells show increased expression of transforming growth factor-beta 3 (TGF beta 3) and altered responses to the antiproliferative effects of TGF beta. J Clin Endocrinol Metab 86:913–920. doi:10.1210/jc.86.2.913
Mahon P, Dupree P (2001) Quantitative and reproducible two-dimensional gel analysis using Phoretix 2D Full. Electrophoresis 22:2075–2085. doi:10.1002/1522-2683(200106)22:10≤2075::AID-ELPS2075≥3.0.CO;2-C
Roth TM, Klett C, Cowan BD (2007) Expression profile of several genes in human myometrium and uterine leiomyoma. Fertil Steril 87:635–641. doi:10.1016/j.fertnstert.2006.10.001
San Martin S, Soto-Suazo M, De Oliveira SF, Aplin JD, Abrahamsohn P, Zorn TM (2003) Small leucine-rich proteoglycans (SLRPs) in uterine tissues during pregnancy in mice. Reproduction 125:585–595. doi:10.1530/rep. 0.1250585
Sun D, Kar S, Carr BI (1995) Differentially expressed genes in TGF-beta 1 sensitive and resistant human hepatoma cells. Cancer Lett 89:73–79
Takahashi N, Takahashi Y, Putnam FW (1985) Periodicity of leucine and tandem repetition of a 24 amino acid segment of the primary structure of leucine rich α2 glycoprotein of human serum. Natl Acad Sci USA 82:1906–1910. doi:10.1073/pnas.82.7.1906
Tang XM, Dou Q, Zhao Y, McLean F, Davis J, Chegini N (1997) The expression of transforming growth factor-beta s and TGF-beta receptor mRNA and protein and the effect of TGF-beta s on human myometrial smooth muscle cells in vivo. Mol Hum Reprod 3:233–240. doi:10.1093/molehr/3.3.233
Xu J, Luo X, Chegini N (2003) Differential expression, regulation, and induction of Smads, transforming growth factor-beta signal transduction pathway in leiomyoma, and myometrial smooth muscle cells and alteration by gonadotropin-releasing hormone analog. J Clin Endocrinol Metab 88:1350–1361. doi:10.1210/jc.2002-021325
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Ferrero, S., Gillott, D.J., Remorgida, V. et al. Increased expression of one isoform of leucine-rich alpha-2-glycoprotein in peritoneal fluid of women with uterine leiomyomas. Arch Gynecol Obstet 279, 365–371 (2009). https://doi.org/10.1007/s00404-008-0741-1
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DOI: https://doi.org/10.1007/s00404-008-0741-1