This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sherwin, J. R. A. Articles by Sharkey, A. M. Search for Related Content PubMed PubMed Citation Articles by Sherwin, J. R. A. Articles by Sharkey, A. M.

Identification of Genes Regulated by Leukemia-Inhibitory Factor in the Mouse Uterus at the Time of Implantation

Department of Pathology (J.R.A.S., S.K.S., A.M.S.), University of Cambridge, Cambridge CB2 1QP; Department of Obstetrics and Gynaecology (J.R.A.S., S.K.S.,), University of Cambridge, The Rosie Hospital, Cambridge CB2 2SW; Microarray Development Group (T.C.F., R.J.S.), United Kingdom Human Genome Mapping Project Resource Centre, Cambridge CB10 1SB; School of Biological Sciences (S.K.), University of Manchester, Manchester M13 9PT; and Centre for Genome Research (A.G.S.. I.C.), University of Edinburgh, Edinburgh EH9 3QJ, Scotland, United Kingdom

Address all correspondence and requests for reprints to: Dr. J. R. A. Sherwin, Department of Obstetrics and Gynaecology, University of Cambridge, Box 223, The Rosie Hospital, Cambridge CB2 2SW, United Kingdom. E-mail: jras100{at}cam.ac.uk.

The endometrium is prepared for implantation by the actions of estradiol (E2) and progesterone (P4). In mice the luminal epithelium (LE) only becomes fully receptive to the attaching blastocyst in response to the nidatory estrogen surge on d 4 of pregnancy. The cytokine leukemia-inhibitory factor (LIF) is rapidly induced by nidatory estrogen and has been shown to be the primary mediator of its action. Implantation fails in the absence of LIF, and injection of LIF on d 4 of pregnancy can substitute for the nidatory estrogen. In this study, we sought to identify genes regulated by LIF in the uterine epithelium. We used oligonucleotide microarrays to compare the transcript profiles of paired uterine horns from LIF-deficient MF1 mice after intraluminal injection of LIF or PBS on d 4 of pseudopregnancy. IGF-binding protein 3 was identified as a gene up-regulated by LIF; this was confirmed by RT-PCR. In situ hybridization showed that the primary site of IGF-binding protein 3 expression is the luminal epithelium (LE), the known site of LIF action in the uterus. We identified two other genes: amphiregulin and immune response gene-1, the expression of which were also up-regulated by LIF. Immune response gene 1 has recently been shown to be essential for implantation. Expression of all three of these genes in the LE is known to be regulated by P4. The expression of osteoblast-specific factor 2 and leukocyte 12/15 lipoxygenase, which are also expressed in LE under the control of P4, were not increased by LIF. This suggests that one of the actions of LIF on LE may be to enhance the expression of a subset of P4-regulated genes.

This article has been cited by other articles:

				A.A Fouladi-Nashta, L Mohamet, J.K Heath, and S.J Kimber Interleukin 1 Signaling Is Regulated by Leukemia Inhibitory Factor (LIF) and Is Aberrant in Lif-/- Mouse Uterus Biol Reprod, July 1, 2008; 79(1): 142 - 153. [Abstract] [Full Text] [PDF]

				L. Aghajanova, K. Bjuresten, S. Altmae, B.-M. Landgren, and A. Stavreus-Evers HB-EGF but Not Amphiregulin or Their Receptors HER1 and HER4 Is Altered in Endometrium of Women With Unexplained Infertility Reproductive Sciences, May 1, 2008; 15(5): 484 - 492. [Abstract] [PDF]

				S J Kimber, S F Sneddon, D J Bloor, A M El-Bareg, J A Hawkhead, A D Metcalfe, F D Houghton, H J Leese, A Rutherford, B A Lieberman, et al. Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors Reproduction, May 1, 2008; 135(5): 635 - 647. [Abstract] [Full Text] [PDF]

				W. V. Ingman and R. L. Jones Cytokine knockouts in reproduction: the use of gene ablation to dissect roles of cytokines in reproductive biology Hum. Reprod. Update, March 1, 2008; 14(2): 179 - 192. [Abstract] [Full Text] [PDF]

				A. A Gratao, M. Dahlhoff, F. Sinowatz, E. Wolf, and M. R Schneider Betacellulin Overexpression in the Mouse Ovary Leads to MAPK3/MAPK1 Hyperactivation and Reduces Litter Size by Impairing Fertilization Biol Reprod, January 1, 2008; 78(1): 43 - 52. [Abstract] [Full Text] [PDF]

				E.A. Campbell, L. O'Hara, R.D. Catalano, A.M. Sharkey, T.C. Freeman, and M. H. Johnson Temporal expression profiling of the uterine luminal epithelium of the pseudo-pregnant mouse suggests receptivity to the fertilized egg is associated with complex transcriptional changes Hum. Reprod., October 1, 2006; 21(10): 2495 - 2513. [Abstract] [Full Text] [PDF]

				E. Dimitriadis, C.A. White, R.L. Jones, and L.A. Salamonsen Cytokines, chemokines and growth factors in endometrium related to implantation Hum. Reprod. Update, November 1, 2005; 11(6): 613 - 630. [Abstract] [Full Text] [PDF]

				S. J Kimber Leukaemia inhibitory factor in implantation and uterine biology Reproduction, August 1, 2005; 130(2): 131 - 145. [Abstract] [Full Text] [PDF]

				R. D. Catalano, M. H. Johnson, E. A. Campbell, D. S. Charnock-Jones, S. K. Smith, and A. M. Sharkey Inhibition of Stat3 activation in the endometrium prevents implantation: A nonsteroidal approach to contraception PNAS, June 14, 2005; 102(24): 8585 - 8590. [Abstract] [Full Text] [PDF]

				G. Schofield and S. J. Kimber Leukocyte Subpopulations in the Uteri of Leukemia Inhibitory Factor Knockout Mice During Early Pregnancy Biol Reprod, April 1, 2005; 72(4): 872 - 878. [Abstract] [Full Text] [PDF]

				F. L Lopes, J. A Desmarais, and B. D Murphy Embryonic diapause and its regulation Reproduction, December 1, 2004; 128(6): 669 - 678. [Abstract] [Full Text] [PDF]