Evidence Supporting the Diethylstilbestrol Induction of Endometriosis Via Immune-Inflammatory Pathway in Rat Model

Evidence Supporting the Diethylstilbestrol Induction of Endometriosis Via Immune-Inflammatory Pathway in Rat Model Life Sciences-Reproductive Biology DOI: https://doi.org/10.22376/ijpbs/lpr.2022.12.5.L66-72Keywords: CA-125, DES, endometriosis, inflammatory pathwayAbstract Endometriosis is a benign reproductive disorder distinguished by chronic inflammation and anomalous progress of stromal cells and glands outside the uterus. Though the etiology of endometriosis is still a matter of debate, the immuneinflammatory mediators are thought to play a major role. Macrophage infiltration and proinflammatory intermediaries in the peritoneal environment peritoneal milieu impact ovarian, uterine function and pelvic morphology, resulting in endometriosis symptoms and signs. The endometriosis model system was developed using diethylstilbestrol (DES) which is examined to develop the disease via the immune-inflammatory pathway. The immune-inflammatory markers (NFKB, MAPK, TNF-α, IL-6 and STAT- 3) were investigated in this study. The results demonstrated that the DES induced endometriosis animal model had a higher level of CA-125, a biomarker of endometriosis. Endometriosis-induced groups had increased levels of NFKB, MAPK, TNF-α, IL-6 and STAT-3 which clearly depicts the immune-inflammatory role in the induction. Finally, the results conclude that DES induced endometriosis via the immune-inflammatory pathway. References Yovich JL, Rowlands PK, Lingham S, Sillender M, Srinivasan S. Pathogenesis of endometriosis: look no further than John Sampson. Reprod Biomed Online. 2020 Jan 1;40(1):7-11. doi: 10.1016/j.rbmo.2019.10.007, PMID 31836436. Sarria-Santamera A, Orazumbekova B, Terzic M, Issanov A, Chaowen C, Asúnsolo-del-Barco A. Systematic review and meta-analysis of incidence and prevalence of endometriosis. Inhealthcare 2020 Dec 30 (Vol. 9, No. 1, p. 29). MDPI. Bouquet de Joliniere J, Major A, Ayoubi JM, Cabry R, Khomsi F, Lesec G et al. It Is Necessary to Purpose an Add-on to the American Classification of Endometriosis? This Disease Can Be Compared to a Malignant Proliferation While Remaining Benign in Most Cases. EndoGram® is a new profile witness of its evolutionary potential. Front Surg. 2019 Jun 7;6:27. doi: 10.3389/fsurg.2019.00027, PMID 31231658. García-Gómez E, Vázquez-Martínez ER, Reyes-Mayoral C, Cruz-Orozco OP, Camacho-Arroyo I, Cerbón M. Regulation of inflammation pathways and inflammasome by sex steroid hormones in endometriosis. Front Endocrinol. 2019;10:935. doi: 10.3389/fendo.2019.00935, PMID 32063886. Leonardi M, Espada M, Choi S, Chou D, Chang T, Smith C et al. Transvaginal ultrasound can accurately predict the American society of reproductive medicine stage of endometriosis assigned at laparoscopy. J Minim Invasive Gynecol. 2020 Nov 1;27(7):1581-1587.e1. doi: 10.1016/j.jmig.2020.02.014, PMID 32126302. Khazaei MR, Rashidi Z, Chobsaz F, Niromand E, Khazaei M. Inhibitory effect of resveratrol on the growth and angiogenesis of human endometrial tissue in an in vitro three-dimensional model of endometriosis. Reprod Biol. 2020 Dec 1;20(4):484-90. doi: 10.1016/j.repbio.2020.07.012, PMID 32896495. Wei Y, Liang Y, Lin H, Dai Y, Yao S. Autonomic nervous system and inflammation interaction in endometriosis-associated pain. J Neuroinflammation. 2020 Dec;17(1):80. doi: 10.1186/s12974-020-01752-1, PMID 32145751. Balasubramanian V, Saravanan R, Joseph LD, Dev B, Gouthaman S, Srinivasan B et al. Molecular dysregulations underlying the pathogenesis of endometriosis. Cell Signal. 2021 Dec 1;88:110139. doi: 10.1016/j.cellsig.2021.110139, PMID 34464692. Thézénas ML, De Leo B, Laux-Biehlmann A, Bafligil C, Elger B, Tapmeier T et al. Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions. Sci Rep. 2020 Jan 30;10(1):1495. doi: 10.1038/s41598-020-58362-3, PMID 32001775. Hudson QJ, Perricos A, Wenzl R, Yotova I. Challenges in uncovering non-invasive biomarkers of endometriosis. Exp Biol Med (Maywood). 2020 Mar;245(5):437-47. doi: 10.1177/1535370220903270, PMID 32019326. Nanda A, K T, Banerjee P, Dutta M, Wangdi T, Sharma P et al. Cytokines, angiogenesis, and extracellular matrix degradation are augmented by oxidative stress in endometriosis. Ann Lab Med. 2020 Sep 1;40(5):390-7. doi: 10.3343/alm.2020.40.5.390, PMID 32311852. Zamora-León P. P. Are the effects of des over? A tragic lesson from the past. Int J Environ Res Public Health. 2021 Sep 30;18(19):10309. doi: 10.3390/ijerph181910309, PMID 34639609. Krishnamoorthy SP, Kalimuthu V, Chandran Manimegalai SC, Arulanandu AM, Thiyagarajan R, Balamuthu K. Evaluation of the potential role of diethylstilbestrol on the induction of endometriosis in a rat model – An alternative approach. Biochem Biophys Res Commun. 2022 Jun 2;617(2):18-24. doi: 10.1016/j.bbrc.2022.05.092, PMID 35689838. Chen SY, Chang TC, Lin CY, Lai CH, Wu RC, Yang LY et al. Serum levels of alpha1-antitrypsin isoforms in patients with ovarian clear cell carcinoma: an exploratory study. J Chin Med Assoc. 2021 Nov 1;84(11):1048-53. doi: 10.1097/JCMA.0000000000000604, PMID 34747901. Sabry D, Mostafa A, Mekawey D, Altaib Z, Shamaa A, Hany A et al. An experimental model: intrauterine adhesion versus subendometrial fibrosis. Biomed Res. 2018;29(17):3311-8. doi: 10.4066/biomedicalresearch.29-18-849. Lu C, Liu Y, Wang X, Jiang H, Liu Z. Tumor necrosis factor receptor type 1-associated death domain (TRADD) regulates epithelial-mesenchymal transition (EMT), M1/M2 macrophage polarization and ectopic endometrial cysts formation in endometriosis. Ann Transl Med. 2021 Jan;9(2):148. doi: 10.21037/atm-20-7866, PMID 33569450. Huang R, Chen S, Zhao M, Li Z, Zhu L. Ginsenoside Rg3 attenuates endometriosis by inhibiting the viability of human ectopic endometrial stromal cells through the nuclear factor-kappaB signaling pathway. J Gynecol Obstet Hum Reprod. 2020 Jan 1;49(1):101642. doi: 10.1016/j.jogoh.2019.101642, PMID 31563698. Thézénas ML, De Leo B, Laux-Biehlmann A, Bafligil C, Elger B, Tapmeier T et al. Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions. Sci Rep. 2020 Jan 30;10(1):1495. doi: 10.1038/s41598-020-58362-3, PMID 32001775. Ersoy B, Hey-Cunningham AJ, Lindsay L, Varol N, Markham R. Altered immune environment in peritoneal endometriotic lesions: relationship to lesion appearance. F S Sci. 2021 May 1;2(2):207-18. doi: 10.1016/j.xfss.2020.11.002, PMID 35559754. Miller JE, Ahn SH, Marks RM, Monsanto SP, Fazleabas AT, Koti M et al. IL-17A modulates peritoneal macrophage recruitment and M2 polarization in endometriosis. Front Immunol. 2020 Feb 14;11:108. doi: 10.3389/fimmu.2020.00108, PMID 32117261. Lai ZZ, Yang HL, Shi JW, Shen HH, Wang Y, Chang KK et al. Protopanaxadiol improves endometriosis associated infertility and miscarriage in sex hormones receptors-dependent and independent manners. Int J Biol Sci. 2021;17(8):1878-94. doi: 10.7150/ijbs.58657, PMID 34131393. Agostinis C, Zorzet S, Balduit A, Zito G, Mangogna A, Macor P et al. Complement component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation. bioRxiv. 2020 Jan 1. Tian Z, Chang XH, Zhao Y, Zhu HL. Current biomarkers for the detection of endometriosis. Chin Med J (Engl). 2020 Oct 5;133(19):2346-52. doi: 10.1097/CM9.0000000000001063, PMID 32858595. Kokot I, Piwowar A, Jędryka M, Sołkiewicz K, Kratz EM. Diagnostic significance of selected serum inflammatory markers in women with advanced endometriosis. Int J Mol Sci. 2021 Feb 25;22(5):2295. doi: 10.3390/ijms22052295, PMID 33669013. Zhou J, Chern BSM, Barton-Smith P, Phoon JWL, Tan TY, Viardot-Foucault V et al. Peritoneal fluid cytokines reveal new insights of endometriosis subphenotypes. Int J Mol Sci. 2020 May 15;21(10):3515. doi: 10.3390/ijms21103515, PMID 32429215. Yu Q, Wang J, Li T, Guo X, Ding S, Che X et al. Recepteur d’origine nantais contributes to the development of endometriosis via promoting epithelial‐mesenchymal transition of a endometrial epithelial cells. J Cell Mol Med. 2021 Feb;25(3):1601-12. doi: 10.1111/jcmm.16261, PMID 33410267. Liu Y, Ma J, Cui D, Fei X, Lv Y, Lin J LncRNA MEG3-210 regulates endometrial stromal cells migration, invasion and apoptosis through p38 MAPK and PKA/SERCA2 signalling via interaction with galectin-1 in endometriosis. Mol Cell Endocrinol. 2020 Aug 1;513:110870. doi: 10.1016/j.mce.2020.110870, PMID 32446846. Li MZ, Wu YH, Ali M, Wu XQ, Nie MF. Endometrial stromal cells treated by tumor necrosis factor‐α stimulate macrophages polarized toward M2 via interleukin‐6 and monocyte chemoattractant protein‐1. J Obstet Gynaecol Res. 2020 Feb;46(2):293-301. doi: 10.1111/jog.14135, PMID 31930665. Kaplan S, Kırıcı P, Türk A. The effects of adalimumab on the rat autotransplantation endometriosis model: A placebo-controlled randomized study. Adv Clin Exp Med. 2022;31(4):417-26. doi: 10.17219/acem/144369, PMID 35040600. Ragab D, Abbas A, Salem R. Increased expression of IL-37 correlates with TNF-α levels and disease stage in endometriosis patients. Egypt J Med Hum Genet. 2022 Dec;23(1):1-7. Matsuzaki S, Pouly JL, Canis M. Persistent activation of signal transducer and activator of transcription 3 via interleukin-6 trans-signaling is involved in fibrosis of endometriosis. Hum Reprod. 2022 May 12;37(7):1489-504. doi: 10.1093/humrep/deac098, PMID 35551394. Zhou M, Xu H, Zhang D, Si C, Zhou X, Zhao H et al. Decreased PIBF1/IL6/p-STAT3 during the mid-secretory phase inhibits human endometrial stromal cell proliferation and decidualization. J Adv Res. 2021 May 1;30:15-25. doi: 10.1016/j.jare.2020.09.002, PMID 34026283. Xin P, Xu X, Deng C, Liu S, Wang Y, Zhou X et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol. 2020 Mar 1;80:106210. doi: 10.1016/j.intimp.2020.106210, PMID 31972425. Kotlyar AM, Mamillapalli R, Flores VA, Taylor HS. Tofacitinib alters STAT3 signaling and leads to endometriosis lesion regression. Mol Hum Reprod. 2021 Apr;27(4):gaab016. doi: 10.1093/molehr/gaab016, PMID 33693775. Pan S, Xie F, Chen W, Zhai Q, Zhu L. Ginkgetin inhibits growth and invasion of endometrial carcinoma by disruption of Janus kinase 1/signal transducers and activators of Transcription 3 and Phosphoinositide-3-Kinase/Protein kinase B pathways. Curr Top Nutraceutical Res. 2020;19(1):77-83. doi: 10.37290/ctnr2641-452X.19:77-83. Published How to Cite Issue Section Copyright (c) 2022 Sathiya Priya Krishnamoorthy, Kadalmani Balamuthu This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.