Evaluation of transforming growth factor-beta 1 concentrations in serum, peritoneal and endometrioma fluid in women operated on for ovarian endometriosis as a biomarker of endometrioma

Objectives: Some studies indicate the role of transforming growth factor-beta 1 (TGF-beta 1) in the development of endometriosis. However, the lack is studies assessed its plasma levels as a biomarker of endometrioma. Therefore, this study aimed to analyze plasma, peritoneal, and endometrioma fluid TGF-beta 1 concentrations in women operated on for ovarian endometriosis.

A cross-sectional cohort study involved 56 women operated on for ovarian endometriosis. Body mass, height, and waist circumference were measured, as well as body mass index (BMI) being calculated. Plasma, peritoneal, and endometrioma fluid TGF-beta 1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA).

Levels TGF-beta 1 were significantly higher in plasma than in both fluids (1286.1 pg/mL vs 114.7 pg/mL; p < 0.001 and 114.7 pg/mL vs 33.6 pg/mL; p < 0.001) and in endometrioma fluid than in peritoneal fluid (114.7 pg/mL vs 33.6 pg/mL; p < 0.001). There were also positive correlations between TGF-beta 1 levels in endometrioma and peritoneal fluids and plasma (r = 0.46; p < 0.001; r = 0.30; p < 0.05, respectively). There were no associations between TGF-beta 1 in plasma, endometrioma, peritoneal fluid, and endometriosis stage.

Our results suggest that plasma TGF-beta 1 concentration can be considered as a biomarker of endometrioma.

TGF-beta-1nutritional statusendometriosis

- Janssen EB, Rijkers ACM, Hoppenbrouwers K, et al. Prevalence of endometriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or chronic pelvic pain: a systematic review. Hum Reprod Update. 2013; 19(5): 570–582. - Kuznetsov L, Dworzynski K, Davies M, et al. Guideline Committee. Diagnosis and management of endometriosis: summary of NICE guidance. BMJ. 2017; 358: j3935. - Becker CM, Bokor A, Heikinheimo O, et al. ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum Reprod Open. 2022; 2022(2): hoac009. - Nisenblat V, Bossuyt PMM, Farquhar C, et al. Imaging modalities for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016; 2(2): CD009591. - Moura AP, Ribeiro HS, Bernardo WM, et al. Accuracy of transvaginal sonography versus magnetic resonance imaging in the diagnosis of rectosigmoid endometriosis: systematic review and meta-analysis. PLoS One. 2019; 14(4): e0214842. - Watkins JC, DiVasta AD, Vitonis AF, et al. A clinical and pathologic exploration of suspected peritoneal endometriotic lesions. Int J Gynecol Pathol. 2021; 40(6): 602–610. - Gupta D, Hull ML, Fraser I, et al. Endometrial biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016; 4(4): CD012165. - Nisenblat V, Prentice L, Bossuyt PMM, et al. Blood biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016; 2016(5): CD012179. - Liu E, Nisenblat V, Farquhar C, et al. Urinary biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2015; 2015(12): CD012019. - Li MO, Wan YY, Sanjabi S, et al. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 2006; 24: 99–146. - Liu Z, Yi L, Du M, et al. Overexpression of TGF-β enhances the migration and invasive ability of ectopic endometrial cells via ERK/MAPK signaling pathway. Exp Ther Med. 2019; 17(6): 4457–4464. - Gao T, Cao Yi, Hu M, et al. The activation of TGF-β signaling promotes cell migration and invasion of ectopic endometrium by targeting NRP2. Reprod Biol. 2022; 22(4): 100697. - Yang HL, Zhou WJ, Chang KK, et al. The crosstalk between endometrial stromal cells and macrophages impairs cytotoxicity of NK cells in endometriosis by secreting IL-10 and TGF-β. Reproduction. 2017; 154(6): 815–825. - Soni UK, Chadchan SB, Kumar V, et al. A high level of TGF-B1 promotes endometriosis development via cell migration, adhesiveness, colonization, and invasiveness†. Biol Reprod. 2019; 100(4): 917–938. - Viganò P, Ottolina J, Bartiromo L, et al. Cellular components contributing to fibrosis in endometriosis: a literature review. J Minim Invasive Gynecol. 2020; 27(2): 287–295. - Sikora J, Smycz-Kubańska M, Mielczarek-Palacz A, et al. The involvement of multifunctional TGF-β and related cytokines in pathogenesis of endometriosis. Immunol Lett. 2018; 201: 31–37. - Lee HJ, Kim H, Ku SY, et al. Transforming growth factor-β1 gene polymorphisms in Korean women with endometriosis. Am J Reprod Immunol. 2011; 66(5): 428–434. - Gueuvoghlanian-Silva BY, Bellelis P, Barbeiro DF, et al. Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease. J Reprod Immunol. 2018; 126: 32–38. - Chang KK, Liu LB, Jin LP, et al. IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis. Cell Death Dis. 2017; 8(3): e2666. - Komiyama Si, Aoki D, Komiyama M, et al. Local activation of TGF-beta1 at endometriosis sites. J Reprod Med. 2007; 52(4): 306–312. - Meng Q, Sun W, Jiang J, et al. Identification of common mechanisms between endometriosis and ovarian cancer. J Assist Reprod Genet. 2011; 28(10): 917–923. - Yu YX, Xiu YL, Chen Xi, et al. Transforming growth factor-beta 1 involved in the pathogenesis of endometriosis through regulating expression of vascular endothelial growth factor under hypoxia. Chin Med J (Engl). 2017; 130(8): 950–956. - Shi LiB, Zhou F, Zhu HY, et al. Transforming growth factor beta1 from endometriomas promotes fibrosis in surrounding ovarian tissues via Smad2/3 signaling. Biol Reprod. 2017; 97(6): 873–882. - Choi HJ, Park MJ, Kim BS, et al. Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression. BMB Rep. 2017; 50(8): 429–434. - Cai X, Shen M, Liu X, et al. Reduced expression of eukaryotic translation initiation factor 3 subunit e and its possible involvement in the epithelial-mesenchymal transition in endometriosis. Reprod Sci. 2018; 25(1): 102–109. - Li MQ, Wang Y, Chang KK, et al. CD4+Foxp3+ regulatory T cell differentiation mediated by endometrial stromal cell-derived TECK promotes the growth and invasion of endometriotic lesions. Cell Death Dis. 2014; 5(10): e1436. - Podgaec S, Rizzo LV, Fernandes LF, et al. CD4(+) CD25(high) Foxp3(+) cells increased in the peritoneal fluid of patients with endometriosis. Am J Reprod Immunol. 2012; 68(4): 301–308. - Young VJ, Brown JK, Maybin J, et al. Transforming growth factor-β induced Warburg-like metabolic reprogramming may underpin the development of peritoneal endometriosis. J Clin Endocrinol Metab. 2014; 99(9): 3450–3459. - Young VJ, Brown JK, Saunders PTK, et al. The peritoneum is both a source and target of TGF-β in women with endometriosis. PLoS One. 2014; 9(9): e106773. - Hanada T, Tsuji S, Nakayama M, et al. Suppressive regulatory T cells and latent transforming growth factor-β-expressing macrophages are altered in the peritoneal fluid of patients with endometriosis. Reprod Biol Endocrinol. 2018; 16(1): 9. - American Society of Reproductive Medicine Revised American Society of Reproductive Medicine classification of endometriosis 1996. Fertil Steril. 1997; 67(5): 817–821. - Pizzo A, Salmeri FM, Ardita FV, et al. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2002; 54(2): 82–87. - Jin L, Ruan X, Jin J, et al. Infertile women with endometriosis possess differences in cytokine levels in various tissues. Gynecol Endocrinol. 2022; 38(6): 523–527. - Janša V, Pušić Novak M, Ban Frangež H, et al. TGFBI as a candidate biomarker for non-invasive diagnosis of early-stage endometriosis. Hum Reprod. 2023; 38(7): 1284–1296. - Nisenblat V, Prentice L, Bossuyt PMM, et al. Blood biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016; 2016(5): CD012179.