Skip to main content
SpringerLink
Log in

Decidualization and Epigenetic Regulation

  • Chapter
  • First Online:
Uterine Endometrial Function

  • 756 Accesses

Abstract

Decidualization is a process of differentiation of the endometrial stromal cells (ESC) accompanied by dramatic changes of cell functions and is necessary for embryo implantation and pregnancy establishment. A number of genes are upregulated or downregulated during decidualization. The present review focused on the involvement of epigenetics (histone modifications, DNA methylation, and microRNAs) in the regulation of gene expression in human ESC during decidualization. Histone modification statuses genome-widely change during decidualization. The main histone modifications are increases of H3K27ac and H3K4me3, which activate transcription, whereas decreases of these histone modifications are quite few. The increases of H3K27ac and H3K4me3 are observed not only in the proximal region but also in the distal promoter regions, suggesting distal enhancer-proximal promoter interactions are involved in the upregulation of gene expression during decidualization. One of the potential roles of the increases in H3K27ac and H3K4me3 during decidualization is to activate the insulin signaling pathway, which contributes to decidualization through the increase of glucose uptake. On the other hand, genome-wide DNA methylation does not remarkably change in human ESC during decidualization. These findings indicate that epigenetic regulation, especially through histone modifications, plays important roles in the decidualization of human ESC.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Salker M, Teklenburg G, Molokhia M, Lavery S, Trew G, Aojanepong T, Mardon HJ, et al. Natural selection of human embryos: impaired decidualization of endometrium disables embryo-maternal interactions and causes recurrent pregnancy loss. PLoS ONE. 2010;5, e10287.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Laird SM, Tuckerman EM, Li TC. Cytokine expression in the endometrium of women with implantation failure and recurrent miscarriage. Reprod Biomed Online. 2006;13:13–23.

    Article  CAS  PubMed  Google Scholar 

  3. Wang W, Taylor RN, Bagchi IC, Bagchi MK. Regulation of human endometrial stromal proliferation and differentiation by C/EBPbeta involves cyclin E-cdk2 and STAT3. Mol Endocrinol. 2012;26:2016–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Aghajanova L, Horcajadas JA, Weeks JL, Esteban FJ, Nezhat CN, Conti M, et al. The protein kinase A pathway-regulated transcriptome of endometrial stromal fibroblasts reveals compromised differentiation and persistent proliferative potential in endometriosis. Endocrinology. 2010;151:1341–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Popovici RM, Kao LC, Giudice LC. Discovery of new inducible genes in in vitro decidualized human endometrial stromal cells using microarray technology. Endocrinology. 2000;141:3510–3.

    Article  CAS  PubMed  Google Scholar 

  6. Matsuoka A, Kizuka F, Lee L, Tamura I, Taniguchi K, Asada H, et al. Progesterone increases manganese superoxide dismutase expression via a cAMP-dependent signaling mediated by non-canonical Wnt5a pathway in human endometrial stromal cells. J Clin Endocrinol Metab. 2010;95:E291–9.

    Article  PubMed  Google Scholar 

  7. Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell. 2007;128:707–19.

    Article  CAS  PubMed  Google Scholar 

  8. Tamura I, Taketani T, Lee L, Kizuka F, Taniguchi K, Maekawa R, et al. Differential effects of progesterone on COX-2 and Mn-SOD expressions are associated with histone acetylation status of the promoter region in human endometrial stromal cells. J Clin Endocrinol Metab. 2011;96:E1073–82.

    Article  PubMed  Google Scholar 

  9. Krusche CA, Vloet AJ, Classen-Linke I, von Rango U, Beier HM, Arlfer J. Class I histone deacetylase expression in the human cyclic endometrium and endometrial adenocarcinomas. Hum Reprod. 2007;22:2956–66.

    Article  CAS  PubMed  Google Scholar 

  10. Sakai N, Maruyama T, Sakurai R, Masuda H, Yamamoto Y, Shimizu A, et al. Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells. J Biol Chem. 2003;278:16675–82.

    Article  CAS  PubMed  Google Scholar 

  11. Grimaldi G, Christian M, Steel JH, Henriet P, Poutanen M, Brosens JJ. Down-regulation of the histone methyltransferase EZH2 contributes to the epigenetic programming of decidualizing human endometrial stromal cells. Mol Endocrinol. 2011;25:1892–903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yamagata Y, Asada H, Tamura I, Lee L, Maekawa R, Taniguchi K, et al. DNA methyltransferase expression in the human endometrium: down-regulation by progesterone and oestrogen. Hum Reprod. 2009;24:1126–32.

    Article  CAS  PubMed  Google Scholar 

  13. Houshdaran S, Zelenko Z, Irwin JC, Giudice LC. Human endometrial DNA methylation is cycle-dependent and is associated with gene expression regulation. Mol Endocrinol. 2014;28:1118–35.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Riggs AD, Martienssen RA, Russo VEA. Introduction. In: Russo VEA, Martienssen RA, Riggs AD, editors. Epigenetic mechanisms of gene regulation. New York: Cold Spring Harbor Laboratory Press; 1996. p. 1–4.

    Google Scholar 

  15. Fischle W, Wang Y, Allis CD. Binary switches and modification cassettes in histone biology and beyond. Nature. 2003;425:475–9.

    Article  CAS  PubMed  Google Scholar 

  16. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010;107:21931–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129:823–37.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang JA, Mortazavi A, Williams BA, Wold BJ, Rothenberg EV. Dynamic transformations of genome-wide epigenetic marking and transcriptional control establish T cell identity. Cell. 2012;149:467–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ballestar E, Wolffe AP. Methyl-CpG-binding proteins. Targeting specific gene repression. Eur J Biochem. 2001;268:1–6.

    Article  CAS  PubMed  Google Scholar 

  20. Yagi S, Hirabayashi K, Sato S, Li W, Takahashi Y, Hirakawa T, et al. DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression. Genome Res. 2008;18:1969–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. He L, Hannon GJ. MicroRNAs; small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.

    Article  CAS  PubMed  Google Scholar 

  22. Tamura I, Asada H, Maekawa R, Tanabe M, Lee L, Taketani T, et al. Induction of IGFBP-1 expression by cAMP is associated with histone acetylation status of the promoter region in human endometrial stromal cells. Endocrinology. 2012;153:5612–21.

    Article  CAS  PubMed  Google Scholar 

  23. Tamura I, Sato S, Okada M, Tanabe M, Lee L, Maekawa R, et al. Importance of C/EBPβ binding and histone acetylation status in the promoter regions for induction of IGFBP-1, PRL and Mn-SOD by cAMP in human endometrial stromal cells. Endocrinology. 2014;155:275–86.

    Article  PubMed  Google Scholar 

  24. Tamura I, Ohkawa Y, Sato T, Suyama M, Jozaki K, Okada M, et al. Genome-wide analysis of histone modifications in human endometrial stromal cells. Mol Endocrinol. 2014;28:1656–69.

    Article  PubMed  Google Scholar 

  25. Pham TH, Benner C, Lichtinger M, Schwarzfischer L, Hu Y, Andreesen R, et al. Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states. Blood. 2012;119:e161–71.

    Article  CAS  PubMed  Google Scholar 

  26. Mikkelsen TS, Xu Z, Zhang X, Wang L, Gimble JM, Lander ES, et al. Comparative epigenomic analysis of murine and human adipogenesis. Cell. 2010;143:156–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tian Y, Jia Z, Wang J, Huang Z, Tang J, Zheng Y, et al. Global mapping of H3K4me1 and H3K4me3 reveals the chromatin state-based cell type-specific gene regulation in human Treg cells. PLoS ONE. 2011;6, e27770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cui K, Zang C, Roh TY, Schones DE, Childs RW, Peng W, et al. Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell. 2009;4:80–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li G, Ruan X, Auerbach RK, Sandhu KS, Zheng M, Wang P, et al. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell. 2012;148:84–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang Y, Wong CH, Birnbaum RY, Li G, Favaro R, Ngan CY, et al. Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations. Nature. 2013;504:306–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Purcell SH, Chi MM, Lanzendorf S, Moley KH. Insulin-stimulated glucose uptake occurs in specialized cells within the cumulus oocyte complex. Endocrinology. 2012;153:2444–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lathi RB, Hess AP, Tulac S, Nayak NR, Conti M, Giudice LC. Dose-dependent insulin regulation of insulin-like growth factor binding protein-1 in human endometrial stromal cells is mediated by distinct signaling pathways. J Clin Endocrinol Metab. 2005;90:1599–606.

    Article  CAS  PubMed  Google Scholar 

  33. Ganeff C, Chatel G, Munaut C, Frankenne F, Foidart JM, Winkler R. The IGF system in in-vitro human decidualization. Mol Hum Reprod. 2009;15:27–38.

    Article  CAS  PubMed  Google Scholar 

  34. Kim JJ, Buzzio OL, Li S, Lu Z. Role of FOXO1A in the regulation of insulin-like growth factor-binding protein-1 in human endometrial cells: interaction with progesterone receptor. Biol Reprod. 2005;73:833–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001;414:799–806.

    Article  CAS  PubMed  Google Scholar 

  36. Frolova AI, Moley KH. Quantitative analysis of glucose transporter mRNAs in endometrial stromal cells reveals critical role of GLUT1 in uterine receptivity. Endocrinology. 2011;152:2123–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Frolova A, Flessner L, Chi M, Kim ST, Foyouzi-Yousefi N, Moley KH. Facilitative glucose transporter type 1 is differentially regulated by progesterone and estrogen in murine and human endometrial stromal cells. Endocrinology. 2009;150:1512–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Qian K, Hu L, Chen C, Li H, Liu N, Li Y, et al. Has-miR-222 is involved in differentiation of endometrial stromal cells in vitro. Endocrinology. 2009;150:4734–43.

    Article  CAS  PubMed  Google Scholar 

  39. Estella C, Herrer I, Moreno-Moya JM, Quinonero A, Martinez S, Pellicer A, et al. miRNA signature and dicer requirement during human endometrial stromal decidualization in vitro. PLoS ONE. 2012;7, e41080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan

    Norihiro Sugino, Isao Tamura, Ryo Maekawa & Kosuke Jozaki

Authors
  1. Norihiro Sugino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Isao Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryo Maekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kosuke Jozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norihiro Sugino .

Editor information

Editors and Affiliations

  1. Kansai Medical University, Osaka 573-1010, Japan

    Hideharu Kanzaki

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Japan

About this chapter

Cite this chapter

Sugino, N., Tamura, I., Maekawa, R., Jozaki, K. (2016). Decidualization and Epigenetic Regulation. In: Kanzaki, H. (eds) Uterine Endometrial Function. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55972-6_8

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-55972-6_8

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-55970-2

  • Online ISBN: 978-4-431-55972-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation