K I, Paiva P, Kovacs G: Interleukin-11, IL-11 receptoralpha and leukemia inhibitory factor areConclusions There is a wealth of evidence to support a role for IL11 in endometrial receptivity [37,38]. IL11 regulates endometrial epithelial cell adhesive properties [15] however the mechanisms by which this occurs are poorly defined. This study has identified membrane-associated proteins ANXA2 and FLOT1 as IL11 downstream targets and suggests that IL11 may regulate endometrial epithelial cell adhesion at least in part via these proteins. Currently there are no biochemical markers of endometrial receptivity. This study suggests that FLOT1 may be useful as a marker of receptivity as it is specifically upregulated in the receptive phase. ANXA2 levels in the endometrium have already been associated with receptivity [20]. It however remains to be elucidated whether FLOT1 and ANXA2 are altered in endometrium during the receptive phase of women with subfertility and therefore indicate their utility as markers of receptivity. Further studies on the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/15501003 roles of FLOT1 and ANXA2 in endometrial epithelial cell adhesion are also required to identify whether both factors may be useful as treatment options for endometrial associated subfertility. This is the first study to demonstrate that proteomics is a powerful approach in identifying plasma membrane proteins that have may have a role in cell adhesion and embryo-endometrial interactions. Our data further defines mechanisms critical for endometrial receptivity and embryo implantation and strengthens the evidence that IL11 is an important regulator of endometrial receptivity. Inadequate adhesion of the blastocyst to the endometrial epithelium results in infertility [38]. Targeting IL11 and its regulated plasma membrane proteinsYap et al. Reproductive Biology and Endocrinology 2011, 9:73 http://www.rbej.com/content/9/1/Page 15 of11.12.13.14.15.16.17.18. 19. 20.21. 22. 23.24. 25.26. 27. 28. 29.30. 31.32.33.dysregulated in endometrium of infertile women with endometriosis during the implantation window. J Reprod Immunol 2006, 69:53-64. Karpovich N, Chobotova K, Carver J, Heath JK, Barlow DH, Mardon HJ: Expression and function of interleukin-11 and its receptor alpha in the human endometrium. Mol Hum Reprod 2003, 9:75-80. Sherwin JR, Smith SK, Wilson A, Sharkey AM: Soluble gp130 is upregulated in the implantation window and shows altered secretion in patients with primary unexplained infertility. J Clin Endocrinol Metab 2002, 87:3953-3960. Dimitriadis E, Sharkey A, Tan Y, Salamonsen L, Sherwin J: Immunolocalisation of phosphorylated STAT3, interleukin 11 and leukaemia inhibitory factor in endometrium of women with unexplained infertility during the implantation window. Reprod Biol Endocrinol 2007, 5:1-8. Makkar G, Ng EH, Yeung WS, Ho PC: Reduced expression of interleukin-11 and interleukin-6 in the periimplantation endometrium of excessive ovarian responders during in vitro fertilization treatment. J Clin Endocrinol Metab 2006, 91:3181-3188. Marwood M, Visser K, Salamonsen LA, Dimitriadis E: Interleukin-11 and leukemia inhibitory factor regulate the adhesion of endometrial epithelial cells: implications in fertility regulation. Endocrinology Capecitabine 2009, 150:2915-2923. Stephens AN, Hannan NJ, Rainczuk A, Meehan KL, Chen J, Nicholls PK, Rombauts LJ, Stanton PG, Robertson DM, Salamonsen LA: Post-translational modifications and protein-specific isoforms in endometriosis revealed by 2D DIGE. J Proteome Res 2010, 9:2438-244.