Abstract
The objective was to investigate the expression of the WNT4 gene in ectopic endometrium and eutopic endometrium (EU) during endometriosis and the relationship of WNT4 expression with the menstrual cycle. Ectopic endometrium and EU tissues were collected from 30 women with pathologically confirmed endometriosis and 30 women without endometriosis. The WNT4 protein and messenger RNA (mRNA) expression levels were measured by fluorescence-based quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot methods. The expression of WNT4 was not significantly correlated with the menstrual cycle, and there were no significant differences when WNT4 expression in proliferative endometrium was compared with that in secretory endometrium within each group. There were no significant differences between the protein and mRNA expression of WNT4 in ectopic endometrium and in EU from participants with endometriosis. The WNT4 expression level in EU was significantly reduced compared with that in normal endometrium of the control group, even when analyzed by the menstrual cycle phase. WNT4 was also downregulated in ectopic lesions. This study provides further evidence supporting the theory of “EU determinism” in the pathogenesis of endometriosis.
Similar content being viewed by others
References
Culley L, Law C, Hudson N, et al. The social and psychological impact of endometriosis on women’s lives: a critical narrative review. Hum Reprod Update. 2013;19(6):625–639.
Matsuzaki S, Maleysson E, Darcha C. Analysis of matrix metalloproteinase-7 expression in eutopic and ectopic endometrium samples from patients with different forms of endometriosis. Hum Reprod. 2010;25(3):742–750.
Pellegrini C, Gori I, Achtari C, et al. The expression of estrogen receptors as well as GREB1, c-MYC, and cyclin D1, estrogenregulated genes implicated in proliferation, is increased in peritoneal endometriosis. Fertil Steril. 2012;98(5):1200–1208.
Ueda M, Yamashita Y, Takehara M, et al. Survivin gene expression in endometriosis. J Clin Endocrinol Metab. 2002;87(7): 3452–3459.
Taipale J, Beachy PA. The hedgehog and WNT signalling pathways in cancer. Nature. 2001;411(6835):349–354.
Sonderegger S, Pollheimer J, Knöfler M. WNT signalling in implantation, decidualisation and placental differentiation—review. Placenta. 2010;31(10):839–847.
Boyer A, Goff AK, Boerboom D. WNT signaling in ovarian follicle biology and tumorigenesis. Trends Endocrinol Metab. 2010; 21(1):25–32.
Yu H, Pask AJ, Shaw G, Renfree MB. Comparative analysis of the mammalian WNT4 promoter. BMC Genomics. 2009;10:416.
Huguet EL, McMahon JA, McMahon AP, Bicknell R, Harris AL. Differential expression of human WNT genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue. Cancer Res. 1994;54(10):2615–2621.
Benhaj K, Akcali KC, Ozturk M. Redundant expression of canonical WNT ligands in human breast cancer cell lines. Oncol Rep. 2006;15(3):701–707.
Garnis C, Campbell J, Davies JJ, Macaulay C, Lam S, Lam WL. Involvement of multiple developmental genes on chromosome 1p in lung tumorigenesis. Hum Mol Genet. 2005;14(4):475–482.
Kaiser S, Park YK, Franklin JL, et al. Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer. Genome Biol. 2007;8(7):R131.
Bui TD, Zhang L, Rees MC, Bicknell R, Harris AL. Expression and hormone regulation of WNT2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma. Br J Cancer. 1997;75(8):1131–1136.
Peltoketo H, Allinen M, Vuosku J, et al. Characterization and expression of the human WNT4; lack of associated germline mutations in high—to moderate—risk breast and ovarian cancer. Cancer Lett. 2004;213(1):83–90.
Uno S, Zembutsu H, Hirasawa A, et al. A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. Nat Genet. 2010;42(8):707–710.
Painter JN, Anderson CA, Nyholt DR, et al. Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nat Genet. 2011;43(1):51–54.
Tulac S, Nayak NR, Kao LC, et al. Identification, characterization, and regulation of the canonical WNT signaling pathway in human endometrium. J Clin Endocrinol Metab. 2003;88(8):3860–3866.
Kao LC, Tulac S, Lobo S, et al. Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002;143(6):2119–2138.
Ercoli A, Ferrandina G, Genuardi M, et al. Microsatellite instability is not related to response to cisplatin-based chemotherapy in cervical cancer. Int J Gynecol Cancer. 2005;15(2):308–311.
Hapangama DK, Turner MA, Drury JA, et al. Endometriosis is associated with aberrant endometrial expression of telomerase and increased telomere length. Hum Reprod. 2008;23(7): 1511–1519.
Pabona JM, Simmen FA, Nikiforov MA, et al. Krüppel-like factor 9 and progesterone receptor coregulation of decidualizing endometrial stromal cells: implications for the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2012;97(3): E376–E392.
Brisken C, Heineman A, Chavarria T, et al. Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev. 2000;14(6):650–654.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Liang, Y., Li, Y., Liu, K. et al. Expression and Significance of WNT4 in Ectopic and Eutopic Endometrium of Human Endometriosis. Reprod. Sci. 23, 379–385 (2016). https://doi.org/10.1177/1933719115602763
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719115602763