Identification of global transcriptome abnormalities and potential biomarkers in eutopic endometria of women with endometriosis: A preliminary study

Zhao,Luyang; Gu,Chenglei; Ye,Mingxia; Zhang,Zhe; Han,Weidong; Fan,Wensheng; Meng,Yuanguang

doi:10.3892/br.2017.902

Identification of global transcriptome abnormalities and potential biomarkers in eutopic endometria of women with endometriosis: A preliminary study

Authors:
- Luyang Zhao
- Chenglei Gu
- Mingxia Ye
- Zhe Zhang
- Weidong Han
- Wensheng Fan
- Yuanguang Meng
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Affiliations: Department of Gynecology and Obstetrics, People's Liberation Army Medical School, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China, Department of Molecular Biology, Institute of Basic Medicine, People's Liberation Army Medical School, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China
Published online on: May 3, 2017 https://doi.org/10.3892/br.2017.902
Pages: 654-662
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The etiology and pathophysiology of endometriosis remain unclear. The aim of the current study was to identify a candidate pathogenic gene, as well as potential biomarkers of endometriosis using messenger RNA (mRNA) sequencing (mRNA-seq). Twenty-three eutopic endometria from women with endometriosis and 20 endometria from control subjects were investigated. Eight eutopic endometria and five normal endometria were selected for mRNA‑seq. Differentially expressed genes (DEGs) were identified and functional analysis was conducted. Validation of certain DEGs was performed in the remaining cases and control subjects by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). A total of 72 DEGs (66 upregulated and 6 downregulated) were identified in samples from women with endometriosis and compared with the control subjects. High DEGs included those involved in various functions, such as extracellular matrix (ECM) remodeling, angiogenesis, cell proliferation and differentiation. Enriched by these DEGs, 100 Gene Ontology terms were identified as significantly important, particularly ‘ECM’ and ‘endogenous stimulus’. Validation using RT‑qPCR indicated that matrix metallopeptidase 11, dual specificity phosphatase 1, Fos proto‑oncogeneand serpin family E member 1 were significantly upregulated and adenosine deaminase 2 was significantly downregulated in the eutopic endometrium of patients with endometriosis. The identified DEGs may be involved in the pathogenesis of endometriosis and may be potential biomarkers in the eutopic endometrium. The current study provides a comprehensive, but preliminary insight for elucidating the mechanisms of endometriosis, which require further in‑depth studies for confirmation.

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1	Kennedy S, Bergqvist A, Chapron C, D'Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A and Saridogan E: ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group: ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 20:2698–2704. 2005. View Article : Google Scholar : PubMed/NCBI
2	Hudelist G, Fritzer N, Thomas A, Niehues C, Oppelt P, Haas D, Tammaa A and Salzer H: Diagnostic delay for endometriosis in Austria and Germany: Causes and possible consequences. Hum Reprod. 27:3412–3416. 2012. View Article : Google Scholar : PubMed/NCBI
3	Sourial S, Tempest N and Hapangama DK: Theories on the pathogenesis of endometriosis. Int J Reprod Med. 2014:1795152014. View Article : Google Scholar : PubMed/NCBI
4	Sampson JA: Metastatic or Embolic Endometriosis, due to the Menstrual Dissemination of Endometrial Tissue into the Venous Circulation. Am J Pathol. 3:93–110.43. 1927.PubMed/NCBI
5	Liu H and Lang JH: Is abnormal eutopic endometrium the cause of endometriosis? The role of eutopic endometrium in pathogenesis of endometriosis. Med Sci Monit. 17:RA92–RA99. 2011.PubMed/NCBI
6	Lattarulo S, Pezzolla A, Fabiano G and Palasciano N: Intestinal endometriosis: Role of laparoscopy in diagnosis and treatment. Int Surg. 94:310–314. 2009.PubMed/NCBI
7	Fassbender A, Vodolazkaia A, Saunders P, Lebovic D, Waelkens E, De Moor B and D'Hooghe T: Biomarkers of endometriosis. Fertil Steril. 99:1135–1145. 2013. View Article : Google Scholar : PubMed/NCBI
8	American Society for Reproductive, . Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 67:817–821. 1997. View Article : Google Scholar : PubMed/NCBI
9	Noyes RW, Hertig AT and Rock J: Dating the endometrial biopsy. Am J Obstet Gynecol. 122:262–263. 1975. View Article : Google Scholar : PubMed/NCBI
10	Chomczynski P and Sacchi N: The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: Twenty-something years on. Nat Protoc. 1:581–585. 2006. View Article : Google Scholar : PubMed/NCBI
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
12	May KE, Villar J, Kirtley S, Kennedy SH and Becker CM: Endometrial alterations in endometriosis: A systematic review of putative biomarkers. Hum Reprod Update. 17:637–653. 2011. View Article : Google Scholar : PubMed/NCBI
13	Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR, Lessey BA and Giudice LC: Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 148:3814–3826. 2007. View Article : Google Scholar : PubMed/NCBI
14	Sherwin JR, Sharkey AM, Mihalyi A, Simsa P, Catalano RD and D'Hooghe TM: Global gene analysis of late secretory phase, eutopic endometrium does not provide the basis for a minimally invasive test of endometriosis. Hum Reprod. 23:1063–1068. 2008. View Article : Google Scholar : PubMed/NCBI
15	Tamaresis JS, Irwin JC, Goldfien GA, Rabban JT, Burney RO, Nezhat C, DePaolo LV and Giudice LC: Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology. 155:4986–4999. 2014. View Article : Google Scholar : PubMed/NCBI
16	Muramatsu T and Miyauchi T: Basigin (CD147): A multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor invasion. Histol Histopathol. 18:981–987. 2003.PubMed/NCBI
17	Pitsos M and Kanakas N: The role of matrix metalloproteinases in the pathogenesis of endometriosis. Reprod Sci. 16:717–726. 2009. View Article : Google Scholar : PubMed/NCBI
18	Gilabert-Estellés J, Ramón LA, España F, Gilabert J, Vila V, Réganon E, Castelló R, Chirivella M and Estellés A: Expression of angiogenic factors in endometriosis: Relationship to fibrinolytic and metalloproteinase systems. Hum Reprod. 22:2120–2127. 2007. View Article : Google Scholar : PubMed/NCBI
19	Ramón L, Gilabert-Estellés J, Castelló R, Gilabert J, España F, Romeu A, Chirivella M, Aznar J and Estellés A: mRNA analysis of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis using a real-time quantitative RT-PCR assay. Hum Reprod. 20:272–278. 2005. View Article : Google Scholar : PubMed/NCBI
20	Uzan C, Cortez A, Dufournet C, Fauvet R, Siffroi JP and Daraï E: Eutopic endometrium and peritoneal, ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases-2, −3 and −11, and of tissue inhibitor metalloproteinases-1 and −2. Virchows Arch. 445:603–609. 2004. View Article : Google Scholar : PubMed/NCBI
21	Cominelli A, Chevronnay HP Gaide, Lemoine P, Courtoy PJ, Marbaix E and Henriet P: Matrix metalloproteinase-27 is expressed in CD163+/CD206+ M2 macrophages in the cycling human endometrium and in superficial endometriotic lesions. Mol Hum Reprod. 20:767–775. 2014. View Article : Google Scholar : PubMed/NCBI
22	Zhao L, Gu C and Meng Y: Meta-analysis of the association between endometriosis and polymorphisms in ACE and PAI-1. Int J Clin Exp Med. 9:10602–10614. 2016.
23	Braza-Boïls A, Marí-Alexandre J, Gilabert J, Sánchez-Izquierdo D, España F, Estellés A and Gilabert-Estellés J: MicroRNA expression profile in endometriosis: Its relation to angiogenesis and fibrinolytic factors. Hum Reprod. 29:978–988. 2014. View Article : Google Scholar : PubMed/NCBI
24	Milde-Langosch K: The Fos family of transcription factors and their role in tumourigenesis. Eur J Cancer. 41:2449–2461. 2005. View Article : Google Scholar : PubMed/NCBI
25	Nemos C, Delage-Mourroux R, Jouvenot M and Adami P: Onset of direct 17-beta estradiol effects on proliferation and c-fos expression during oncogenesis of endometrial glandular epithelial cells. Exp Cell Res. 296:109–122. 2004. View Article : Google Scholar : PubMed/NCBI
26	Pan H, Sheng JZ, Tang L, Zhu R, Zhou TH and Huang HF: Increased expression of c-fos protein associated with increased matrix metalloproteinase-9 protein expression in the endometrium of endometriotic patients. Fertil Steril. 90:1000–1007. 2008. View Article : Google Scholar : PubMed/NCBI
27	Morsch DM, Carneiro MM, Lecke SB, Araújo FC, Camargos AF, Reis FM and Spritzer PM: c-fos gene and protein expression in pelvic endometriosis: A local marker of estrogen action. J Mol Histol. 40:53–58. 2009. View Article : Google Scholar : PubMed/NCBI
28	O'Donovan KJ, Tourtellotte WG, Millbrandt J and Baraban JM: The EGR family of transcription-regulatory factors: Progress at the interface of molecular and systems neuroscience. Trends Neurosci. 22:167–173. 1999. View Article : Google Scholar : PubMed/NCBI
29	Birt JA, Nabli H, Stilley JA, Windham EA, Frazier SR and Sharpe-Timms KL: Elevated peritoneal fluid TNF-α incites ovarian early growth response factor 1 expression and downstream protease mediators: A correlation with ovulatory dysfunction in endometriosis. Reprod Sci. 20:514–523. 2013. View Article : Google Scholar : PubMed/NCBI
30	Djokovic D and Calhaz-Jorge C: Angiogenesis as a therapeutic target in endometriosis. Acta Med Port. 27:489–497. 2014. View Article : Google Scholar : PubMed/NCBI
31	Groothuis PG, Nap AW, Winterhager E and Grümmer R: Vascular development in endometriosis. Angiogenesis. 8:147–156. 2005. View Article : Google Scholar : PubMed/NCBI
32	Taylor RN, Yu J, Torres PB, Schickedanz AC, Park JK, Mueller MD and Sidell N: Mechanistic and therapeutic implications of angiogenesis in endometriosis. Reprod Sci. 16:140–146. 2009. View Article : Google Scholar : PubMed/NCBI
33	Bourlev V, Volkov N, Pavlovitch S, Lets N, Larsson A and Olovsson M: The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions. Reproduction. 132:501–509. 2006. View Article : Google Scholar : PubMed/NCBI
34	de Iaco P, Marabini A, Stefanetti M, Del Vecchio C and Bovicelli L: Acceptability and pain of outpatient hysteroscopy. J Am Assoc Gynecol Laparosc. 7:71–75. 2000. View Article : Google Scholar : PubMed/NCBI
35	Nisolle M, Paindaveine B, Bourdon A, Berlière M, Casanas-Roux F and Donnez J: Histologic study of peritoneal endometriosis in infertile women. Fertil Steril. 53:984–988. 1990. View Article : Google Scholar : PubMed/NCBI