Skip to main content
Log in

Effects of Ido1 on mouse decidualization

  • Cell Molecular Biology
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme which converts the essential amino acid tryptophan to kynurenine. The aim of this study was to investigate the expression and regulation of Ido1 in mouse uterus during decidualization. The results showed that Ido1 mRNA expression gradually increased from day 1 to 4 of pregnancy and reached the peak level on day 4. On days 5–8 of pregnancy, a low level of Ido1 expression was observed in the uteri. Simultaneously, Ido1 mRNA was also lowly expressed in the decidualized uterus and the stromal cells treated with 8-Br-cAMP. Under in vitro decidualization, the expression of Ido1 mRNA gradually declined. Further studies found that overexpression of Ido1 can inhibit the expression of decidualization marker genes PRL, IGFBP1 and Dtprp under in vitro decidualization while inhibition of Ido1 with L-1-MT can induce the expression of these marker genes. Ido1 can prevent uterine stromal cells proliferation and enhance the expression of the Bax gene and increase the Bax/Bcl2 ratio under in vitro decidualization. Additionally, Ido1 can also modulate the expression of the MMP2 gene. In the uterine stromal cells, estrogen and progesterone can stimulate the expression of Ido1. These data indicate that Ido1 may play an important role during mouse decidualization and may be regulated by estrogen and progesterone in the uterine stromal cells.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Das S.K. 2009. Cell cycle regulatory control for uterine stromal cell decidualization in implantation. Reproduction. 137, 889–899.

    Article  CAS  PubMed  Google Scholar 

  2. Zhang S., Lin H., Kong S., Wang S., Wang H., Wang H., Armant D.R. 2013. Physiological and molecular determinants of embryo implantation. Mol. Aspects Med. 34, 939–980.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Shao J., Li M.Q., Meng Y.H., Chang K.K., Wang Y., Zhang L., Li D.J. 2013. Estrogen promotes the growth of decidual stromal cells in human early pregnancy. Mol. Hum. Reprod. 19, 655–664.

    Article  CAS  PubMed  Google Scholar 

  4. Stone T.W., Darlington L.G. 2002. Endogenous kynurenines as targets for drug discovery and development. Nat. Rev. Drug Discov. 1, 609–620.

    Article  CAS  PubMed  Google Scholar 

  5. Entrican G., Wattegedera S., Rocchi M., Wheelhouse N. 2009. Pregnancy, indoleamine 2,3-dioxygenase (IDO) and chlamydial abortion: An unresolved paradox. Vet. Microbiol. 135, 98–102.

    Article  CAS  PubMed  Google Scholar 

  6. Palafox D., Llorente L., Alberu J., Torres-Machorro A., Camorlinga N., Rodríguez C., Granados J. 2010. The role of indoleamine 2,3 dioxygenase in the induction of immune tolerance in organ transplantation. Transplant. Rev. 24, 160–165.

    Article  Google Scholar 

  7. Soliman H., Mediavilla-Varela M., Antonia S. 2010. Indoleamine 2,3-dioxygenase: Is it an immune suppressor? Cancer J. 16, 354–359.

    Article  CAS  PubMed  Google Scholar 

  8. Mei J., Li M.Q., Ding D., Li D.J., Jin L.P., Hu W.G., Zhu X.Y. 2013. Indoleamine 2,3-dioxygenase-1 (IDO1) enhances survival and invasiveness of endometrial stromal cells via the activation of JNK signaling pathway. Int. J. Clin. Exp. Pathol. 6, 431–444.

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Munn D.H. 2006. Indoleamine 2,3-dioxygenase, tumor-induced tolerance and counter-regulation. Curr. Opin. Immunol. 18, 220–225.

    Article  CAS  PubMed  Google Scholar 

  10. Munn D.H., Zhou M., Attwood J.T., Bondarev I., Conway S.J., Marshall B., Brown C., Mellor A.L. 1998. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 281, 1191–1193.

    Article  CAS  PubMed  Google Scholar 

  11. Baban B., Chandler P., Mc Cool D., Marshall B., Munn D.H., Mellor A.L. 2004. Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific. J. Reprod. Immunol. 61, 67–77.

    Article  CAS  PubMed  Google Scholar 

  12. Sedlmayr P., Blaschitz A., Wintersteiger R., Semlitsch M., Hammer A., Mac Kenzie C.R., Walcher W., Reich O., Takikawa O., Dohr G. 2002. Localization of indoleamine 2,3-dioxygenase in human female reproductive organs and the placenta. Mol. Hum. Reprod. 8, 385–391.

    Article  CAS  PubMed  Google Scholar 

  13. Britan A., Maffre V., Tone S., Drevet J.R. 2006. Quantitative and spatial differences in the expression of tryptophan-metabolizing enzymes in mouse epididymis. Cell Tissue Res. 324, 301–310.

    Article  CAS  PubMed  Google Scholar 

  14. Mei J., Jin L.P., Ding D., Li M.Q., Li D.J., Zhu X.Y. 2012. Inhibition of IDO1 suppresses cyclooxygenase-2 and matrix metalloproteinase-9 expression and decreases proliferation, adhesion and invasion of endometrial stromal cells. Mol. Hum. Reprod. 18, 467–476.

    Article  CAS  PubMed  Google Scholar 

  15. Kudo Y., Hara T., Katsuki T., Toyofuku A., Katsura Y., Takikawa O., Fujii T., Ohama K. 2004. Mechanisms regulating the expression of indoleamine 2,3-dioxygenase during decidualization of human endometrium. Hum. Reprod. 19, 1222–1230.

    Article  CAS  PubMed  Google Scholar 

  16. Saito S., Shima T., Nakashima A., Shiozaki A., Ito M., Sasaki Y. 2007. What is the role of regulatory T cells in the success of implantation and early pregnancy? J. Assist. Reprod. Genet. 24, 379–386.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Jeddi-Tehrani M., Abbasi N., Dokouhaki P., Ghasemi J., Rezania S., Ostadkarampour M., Rabbani H., Akhondi M.A., Fard Z.T., Zarnani A.H. 2009. Indoleamine 2,3-dioxygenase is expressed in the endometrium of cycling mice throughout the oestrous cycle. J. Reprod. Immunol. 80, 41–48.

    Article  CAS  PubMed  Google Scholar 

  18. Tian X.C., Wang Q.Y., Li D.D., Wang S.T., Yang Z.Q., Guo B., Yue Z.P. 2013. Differential expression and regulation of Cryab in mouse uterus during preimplantation period. Reproduction. 145, 577–585.

    Article  CAS  PubMed  Google Scholar 

  19. Gellersen B., Brosens J. 2003. Cyclic AMP and progesterone receptor cross-talk in human endometrium: A decidualizing affair. J. Endocrinol. 178, 357–372.

    Article  CAS  PubMed  Google Scholar 

  20. McKiernan S.H., Clayton M.K., Bavister B.D. 1995. Analysis of stimulatory and inhibitory amino acids for development of hamster one-cell embryos in vitro. Mol. Reprod. Dev. 42, 188–199.

    Article  CAS  PubMed  Google Scholar 

  21. Doherty L.F., Kwon H.E., Taylor H.S. 2011. Regulation of tryptophan 2,3-dioxygenase by HOXA10 enhances embryo viability through serotonin signaling. Am. J. Physiol. Endocrinol. Metab. 300, E86–E93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Favre D., Mold J., Hunt P.W., Kanwar B., Loke P., Seu L., Barbour J.D., Lowe M.M., Jayawardene A., Aweeka F., Huang Y., Douek D.C., Brenchley J.M., Martin J.N., Hecht F.M., Deeks S.G., Mc Cune J.M. 2010. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci. Transl. Med. 2, 32ra36.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Miwa N., Hayakawa S., Miyazaki S., Myojo S., Sasaki Y., Sakai M., Takikawa O., Saito S. 2005. IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-gamma increase in normal pregnancy but decrease in spontaneous abortion. Mol. Hum. Reprod. 11, 865–870.

    Article  CAS  PubMed  Google Scholar 

  24. Suzuki S., Toné S., Takikawa O., Kubo T., Kohno I., Minatogawa Y. 2001. Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early conception. Biochem. J. 355, 425–429.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Minatogawa Y., Suzuki S., Ando Y., Tone S., Takikawa O. 2003. Tryptophan pyrrole ring cleavage enzymes in placenta. Adv. Exp. Med. Biol. 527, 425–434.

    Article  CAS  PubMed  Google Scholar 

  26. Li D.D., Gao Y.J., Tian X.C., Yang Z.Q., Cao H., Zhang Q.L., Guo B., Yue Z.P. 2013. Differential expression and regulation of Tdo2 during mouse decidualization. J. Endocrinol. 220, 73–83.

    Article  PubMed  Google Scholar 

  27. McConaha M.E., Eckstrum K., An J., Steinle J.J., Bany B.M. 2011. Microarray assessment of the influence of the conceptus on gene expression in the mouse uterus during decidualization. Reproduction. 141, 511–527.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Akcali K.C., Khan S.A., Moulton B.C. 1996. Effect of decidualization on the expression of bax and bcl-2 in the rat uterine endometrium. Endocrinology. 137, 3123–3131.

    CAS  PubMed  Google Scholar 

  29. Dai D., Moulton B.C., Ogle T.F. 2000. Regression of the decidualized mesometrium and decidual cell apoptosis are associated with a shift in expression of Bcl2 family members. Biol. Reprod. 63, 188–195.

    Article  CAS  PubMed  Google Scholar 

  30. Nuttall R.K., Kennedy T.G. 2000. Epidermal growth factor and basic fibroblast growth factor increase the production of matrix metalloproteinases during in vitro decidualization of rat endometrial stromal cells. Endocrinology. 141, 629–636.

    Article  CAS  PubMed  Google Scholar 

  31. Alexander C.M., Hansell E.J., Behrendtsen O., Flannery M.L., Kishnani N.S., Hawkes S.P., Werb Z. 1996. Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation. Development. 122, 1723–1736.

    CAS  PubMed  Google Scholar 

  32. Chen L., Belton R.J Jr., Nowak R.A. 2009. Basiginmediated gene expression changes in mouse uterine stromal cells during implantation. Endocrinology. 150, 966–976.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Zhu W.H., Lu C.Z., Huang Y.M., Link H., Xiao B.G. 2007. A putative mechanism on remission of multiple sclerosis during pregnancy: Estrogen-induced indoleamine 2,3-dioxygenase by dendritic cells. Mult. Scler. 13, 33–40.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. Guo.

Additional information

The article is published in the original.

These authors contributed equaly to this work.

Published in Russian in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 4, pp. 649–657.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, DD., Yin, YH., Wu, JY. et al. Effects of Ido1 on mouse decidualization. Mol Biol 49, 581–588 (2015). https://doi.org/10.1134/S0026893315030127

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893315030127

Keywords

Navigation