Icaritin inhibits decidualization of endometrial stromal cells

Le,Aiwen; Wang,Zhong  Hai; Dai,Xiao  Yun; Xiao,Tian  Hui; Zhuo,Rong; Zhang,Baozhen; Xiao,Zhonglin; Fan,Xiujun

doi:10.3892/etm.2017.5278

Icaritin inhibits decidualization of endometrial stromal cells

Authors:
- Aiwen Le
- Zhong Hai Wang
- Xiao Yun Dai
- Tian Hui Xiao
- Rong Zhuo
- Baozhen Zhang
- Zhonglin Xiao
- Xiujun Fan
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Affiliations: Department of Obstetrics and Gynecology, Affiliated Shenzhen Nanshan People's Hospital of Guangdong Medical University, Shenzhen, Guangdong 518052, P.R. China, Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, P.R. China
Published online on: October 10, 2017 https://doi.org/10.3892/etm.2017.5278
Pages: 5949-5955
Copyright: © Le et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the effects of Icaritin on the proliferation and decidualization of endometrial stromal cells (ESCs). A total of 20 specimens of endometrium were collected during hysterectomy at the Gynecology Department of Shenzhen Nanshan People's Hospital (Shenzhen, China) between August 2014 and December 2015. The endometrium was digested with high concentrations of collagenase and DNase and filtered with meshes, and then the glandular epithelial and stromal cells were separated by the adhesion purification method. The purity of stromal cells was identified by vimetin and cytokeratin 7 immunostaining. The estradiol + progesterone (E2+P4) and/or cyclic adenosine monophosphate (cAMP) were added to induce an in vitro decidualization model, which was used to analyze the effect of Icaritin on the decidualization ability of the human ESCs. The decidualization markers of human ESCs, prolactin (PRL) and insulin‑like growth factor‑binding protein 1 (IGFBP‑1), was analyzed by reverse‑transcription quantitative polymerase chain reaction measurements of the mRNA levels, PRL immunostaining and ELISA analysis of the IGFBP‑1 protein levels in the cells or cell culture supernatant separately. The results demonstrated that treatment with E2+P4 and/or cAMP for 96 h was able to induce decidualization in ESCs, and that the cells demonstrated polygon‑shaped epithelioid changes. The cell nuclei revealed multinuclear changes, and the cells were also observed to be large and round in shape. The PRL expression and upregulated IGFBP‑1 mRNA and protein levels in the E2+P4+cAMP treatment group indicated successful decidualization of the in vitro model. However, the addition of Icaritin inhibited the expression of PRL and IGFBP‑1 mRNA, as well as IGFBP‑1 protein in the induced ESCs compared with groups without Icaritin. These results suggest that Icaritin was able to inhibit the expression of decidualization‑related genes in ESCs in vitro. However, the exact mechanisms require further investigation.

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1	Riad ON and Hak AA: Assessment of endometrial receptivity using Doppler ultrasonography in infertile women undergoing intrauterine insemination. Gynecol Endocrinol. 30:70–73. 2014. View Article : Google Scholar : PubMed/NCBI
2	Gleicher N, Vidali A and Barad DH: Successful treatment of unresponsive thin endometrium. Fertil Steril. 95:2123.e13–e17. 2011. View Article : Google Scholar
3	Aydin T, Kara M and Nurettin T: Relationship between endometrial thickness and in vitro Fertilization-intracytoplasmic sperm injection outcome. Int J Fertil Steril. 7:29–34. 2013.PubMed/NCBI
4	Gargett CE and Healy DL: Generating receptive endometrium in Asherman's syndrome. J Hum Reprod Sci. 4:49–52. 2011.PubMed/NCBI
5	Deligdisch L: Hormonal pathology of the endometrium. Mod Pathol. 13:285–294. 2000. View Article : Google Scholar : PubMed/NCBI
6	Ramathal CY, Bagchi IC, Taylor RN and Bagchi MK: Endometrial decidualization: Of mice and men. Semin Reprod Med. 28:17–26. 2010. View Article : Google Scholar : PubMed/NCBI
7	Schwab KE, Chan RW and Gargett CE: Putative stem cell activity of human endometrial epithelial and stromal cells during the menstrual cycle. Fertil Steril. 84 Suppl 2:S1124–S1130. 2005. View Article : Google Scholar
8	Dunn CL, Kelly RW and Critchley HO: Decidualization of the human endometrial stromal cell: An enigmatic transformation. Reprod Biomed Online. 7:151–161. 2003. View Article : Google Scholar : PubMed/NCBI
9	Kane NM, Jones M, Brosens JJ, Kelly RW, Saunders PT and Critchley HO: TGFβ1 attenuates expression of prolactin and IGFBP-1 in decidualized endometrial stromal cells by both SMAD-dependent and SMAD-independent pathways. PLoS One. 5:e129702010. View Article : Google Scholar : PubMed/NCBI
10	Guzel E, Buchwalder L, Basar M, Kayisli U, Ocak N, Bozkurt I, Lockwood CJ and Schatz F: Effects of tibolone and its metabolites on prolactin and insulin-like growth factor binding protein-1 expression in human endometrial stromal cells. Gynecol Endocrinol. 31:414–418. 2015. View Article : Google Scholar : PubMed/NCBI
11	Liang DK, Qi HB, Luo X, Xiao XQ and Jia XY: Comparative study of placental α-microglobulin-1, insulin-like growth factor binding protein-1 and nitrazine test to diagnose premature rupture of membranes: A randomized controlled trial. J Obstet Gynaecol Res. 40:1555–1560. 2014. View Article : Google Scholar : PubMed/NCBI
12	Ammoun S, Schmid MC, Zhou L, Ristic N, Ercolano E, Hilton DA, Perks CM and Hanemann CO: Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates human schwannoma proliferation, adhesion and survival. Oncogene. 31:1710–1722. 2012. View Article : Google Scholar : PubMed/NCBI
13	Lóránd T, Vigh E and Garai J: Hormonal action of plant derived and anthropogenic non-steroidal estrogenic compounds: Phytoestrogens and xenoestrogens. Curr Med Chem. 17:3542–3574. 2010. View Article : Google Scholar : PubMed/NCBI
14	Ma HP, Ming LG, Ge BF, Zhai YK, Song P, Xian CJ and Chen KM: Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro. J Cell Biochem. 112:916–923. 2011. View Article : Google Scholar : PubMed/NCBI
15	Ye HY and Lou YJ: Estrogenic effects of two derivatives of icariin on human breast cancer MCF-7 cells. Phytomedicine. 12:735–741. 2005. View Article : Google Scholar : PubMed/NCBI
16	Pierro E, Minici F, Alesiani O, Miceli F, Proto C, Screpanti I, Mancuso S and Lanzone A: Stromal-epithelial interactions modulate estrogen responsiveness in normal human endometrium. Biol Reprod. 64:831–838. 2001. View Article : Google Scholar : PubMed/NCBI
17	Kusama K, Yoshie M, Tamura K, Kodaka Y, Hirata A, Sakurai T, Bai H, Imakawa K, Nishi H, Isaka K, et al: Regulation of decidualization in human endometrial stromal cells through exchange protein directly activated by cyclic AMP (Epac). Placenta. 34:212–221. 2013. View Article : Google Scholar : PubMed/NCBI
18	Zhang Y, Lin X, Dai Y, Hu X, Zhu H, Jiang Y and Zhang S: Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways. Reproduction. 152:389–402. 2016. View Article : Google Scholar : PubMed/NCBI
19	Fatemi HM and Popovic-Todorovic B: Implantation in assisted reproduction: A look at endometrial receptivity. Reprod Biomed Online. 27:530–538. 2013. View Article : Google Scholar : PubMed/NCBI
20	Li T, He H, Liu R, Wang SX and Pu DM: Isolation and identification of epithelial and stromal stem cells from eutopic endometrium of women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 178:89–94. 2014. View Article : Google Scholar : PubMed/NCBI
21	Chan RW, Schwab KE and Gargett CE: Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod. 70:1738–1750. 2004. View Article : Google Scholar : PubMed/NCBI
22	Franco HL, Dai D, Lee KY, Rubel CA, Roop D, Boerboom D, Jeong JW, Lydon JP, Bagchi IC, Bagchi MK and DeMayo FJ: WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse. FASEB J. 25:1176–1187. 2011. View Article : Google Scholar : PubMed/NCBI
23	Gellersen B, Brosens IA and Brosens JJ: Decidualization of the human endometrium: Mechanisms, functions, and clinical perspectives. Semin Reprod Med. 25:445–453. 2007. View Article : Google Scholar : PubMed/NCBI
24	Cha J, Sun X and Dey SK: Mechanisms of implantation: Strategies for successful pregnancy. Nat Med. 18:1754–1767. 2012. View Article : Google Scholar : PubMed/NCBI
25	Logan PC, Ponnampalam AP, Steiner M and Mitchell MD: Effect of cyclic AMP and estrogen/progesterone on the transcription of DNA methyltransferases during the decidualization of human endometrial stromal cells. Mol Hum Reprod. 19:302–312. 2012. View Article : Google Scholar : PubMed/NCBI
26	Latil A, Bièche I, Vidaud D, Lidereau R, Berthon P, Cussenot O and Vidaud M: Evaluation of androgen, estrogen (ER alpha and ER beta), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays. Cancer Res. 61:1919–1926. 2001.PubMed/NCBI
27	Gellersen B and Brosens JJ: Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev. 35:851–905. 2014. View Article : Google Scholar : PubMed/NCBI
28	Carden D, Xiao F, Moak C, Willis BH, Robinson-Jackson S and Alexander S: Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins. Am J Physiol. 275:H385–H392. 1998.PubMed/NCBI
29	Lee K, Jeong J, Tsai MJ, Tsai S, Lydon JP and DeMayo FJ: Molecular mechanisms involved in progesterone receptor regulation of uterine function. J Steroid Biochem Mol Biol. 102:41–50. 2006. View Article : Google Scholar : PubMed/NCBI
30	Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P and Stricker R: Establishment of detailed reference values for luteinizing hormone, follicle, stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer. Clin Chem Lab Med. 44:883–887. 2006. View Article : Google Scholar : PubMed/NCBI
31	Tan J, Paria BC, Dey SK and Das SK: Differential uterine expression of estrogen and progesterone receptors correlates with uterine preparation for implantation and decidualization in the mouse. Endocrinology. 140:5310–5321. 1999. View Article : Google Scholar : PubMed/NCBI
32	Curtis Hewitt S, Goulding EH, Eddy EM and Korach KS: Studies using the estrogen receptor alpha knockout uterus demonstrate that implantation but not decidualization-associated signaling is estrogen dependent. Biol Reprod. 67:1268–1277. 2002. View Article : Google Scholar : PubMed/NCBI
33	Hatayama H, Kanzaki H, Iwai M, Kariya M, Fujimoto M, Higuchi T, Kojima K, Nakayama H, Mori T and Fujita J: Progesterone enhances macrophage colony-stimulating factor production in human endometrial stromal cells in vitro. Endocrinology. 135:1921–1927. 1994. View Article : Google Scholar : PubMed/NCBI
34	Kang HK, Lee SB, Kwon H, Sung CK, Park YI and Dong MS: Peripubertal administration of icariin and icaritin advances pubertal development in female rats. Biomol Ther (Seoul). 20:189–195. 2012. View Article : Google Scholar : PubMed/NCBI
35	Bin Wu: Preliminary study on the effect of estrogen on the spontaneous pregnancy and the process of pregnancy (unpublished PhD thesis). Peking Union Medical College. 2014.