Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor


A CRITICAL point during mammalian pregnancy is the implantation of the blastocyst when the embryo attaches to the wall of the uterus. The autonomously developing preimplantation embryo then becomes dependent on the maternal environment for its continued development. Little is known about the regulation of implantation, except that a complex interaction between peptide and steroid hormones synchronizes the preparation of the uterus for implantation with the development of the embryo. Whether the implantation event is under maternal or embryonic control is also unclear (reviewed in refs 1, 2). We have previously shown that a cytokine, leukaemia inhibitory factor (LIF), is expressed in the uterine endometrial glands specifically on the fourth day of pregnancy3. This burst of expression is under maternal control and always precedes implantation of the blastocyst. Here we report that transient expression of LIF in mice is essential for implantation. Females lacking a functional LIF gene are fertile, but their blastocysts fail to implant and do not develop. The blastocysts, however, are viable and, when transferred to wild-type pseudopregnant recipients, they can implant and develop to term.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout


  1. Weitlauf, H. M. in The Physiology of Reproduction (eds Knobil, E. et al.) 231–261 (Raven, New York. 1988).

    Google Scholar 

  2. Hodgen, G. D. & Itskovitz, J. in The Physiology of Reproduction (eds Knobil, E. et al.) 1995–2021 (Raven, New York, 1988).

    Google Scholar 

  3. Bhatt, H., Brunet, L. J. & Stewart, C. L. Proc. natn. Acad. Sci. U.S.A. 88, 11408–11412 (1991).

    Article  ADS  CAS  Google Scholar 

  4. Gearing, D. P. et al. EMBO J. 6, 3995–4001 (1987).

    Article  CAS  Google Scholar 

  5. Thompson, S. et al. Cell 56, 313–321 (1989).

    Article  CAS  Google Scholar 

  6. Zjilstra, M. et al. Nature 344, 742–746 (1990).

    Article  ADS  Google Scholar 

  7. McMahon, A. P. & Bradley, A. Cell 62, 1073–1085 (1990).

    Article  CAS  Google Scholar 

  8. Capecchi, M. R. Science 244, 1288–1292 (1989).

    Article  ADS  CAS  Google Scholar 

  9. Williams, R. L. et al. Nature 336, 684–686 (1988).

    Article  ADS  CAS  Google Scholar 

  10. Smith, A. G. et al. Nature 336, 688–690 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Matsui, V. et al. Nature 353, 750–752 (1991).

    Article  ADS  CAS  Google Scholar 

  12. Murray, R., Lee, F. & Chi, C. P. Molec. cell. Biol. 10, 4953–4956 (1990).

    Article  CAS  Google Scholar 

  13. Conquet, F. & Brulet, F. Molec. cell. Biol. 10, 3801–3805 (1990).

    Article  CAS  Google Scholar 

  14. Hilton, D. J., Wearing, P. M., Nicola, N. A. & Metcalf, D. J. Cell Physiol. 148, 430–439 (1991).

    Article  CAS  Google Scholar 

  15. Hilton, D. J. Trends Biochem. 17, 72–76 (1992).

    Article  CAS  Google Scholar 

  16. Bazan, J. F. Neuron 7, 197–208 (1991).

    Article  CAS  Google Scholar 

  17. Rose, T. M. & Bruce, A. G. Proc. natn. Acad. Sci. U.S.A. 88, 8641–8645 (1991).

    Article  ADS  CAS  Google Scholar 

  18. Gearing, D. P. & Bruce, A. G. New Biol. 4, 61–64 (1992).

    CAS  PubMed  Google Scholar 

  19. Ip, N. Y. et al. Cell 69, 1–11 (1992).

    Article  Google Scholar 

  20. Pampfer, S., Arcedi, R. J. & Pollard, J. W. Bioessays 13, 535–540 (1991).

    Article  CAS  Google Scholar 

  21. Pollard, J. W. et al. Nature 390, 484–486 (1987).

    Article  ADS  Google Scholar 

  22. Regenstreif, L. J. & Rossant, J. Devl Biol. 133, 284–294 (1989).

    Article  CAS  Google Scholar 

  23. Pollard, J. W., Hunt, J. S., Jedrejczak, W. W. & Stanley, E. R. Devl Biol. 148, 273–283 (1991).

    Article  CAS  Google Scholar 

  24. Tartakovsky, B. & Ben-Yair, E. Devl Biol. 146, 345–352 (1991).

    Article  CAS  Google Scholar 

  25. Mansour, S. L., Thomas, K. R. & Capecchi, M. R. Nature 336, 348–352 (1988).

    Article  ADS  CAS  Google Scholar 

  26. Stahl, J. et al. J. biol. Chem. 265, 8833–8841 (1990).

    CAS  PubMed  Google Scholar 

  27. Stewart, C. L., Schuetze, S., Vanek, M. & Wagner, E. F. EMBO J. 6, 383–388 (1987).

    Article  CAS  Google Scholar 

  28. Koëntgen, F. thesis, Univ. Freibourg, Germany (1992).

  29. Bradley, A. in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach (ed. Robertson, E. J.) 113–151 (IRL, Oxford, 1987).

    Google Scholar 

  30. Robertson, E. J. in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach (ed. Robertson, E. J.) 71–112 (IRL, Oxford, 1987).

    Google Scholar 

  31. Sambrook, J., Frisch, E. F. & Maniatis, T. in Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Stewart, C., Kaspar, P., Brunet, L. et al. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 359, 76–79 (1992).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing