Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 299 (5605): 405-408

Copyright © 2003 by the American Association for the Advancement of Science

Trophoblast L-Selectin-Mediated Adhesion at the Maternal-Fetal Interface

Olga D. Genbacev,1 Akraporn Prakobphol,1 Russell A. Foulk,4 Ana R. Krtolica,5 Dusko Ilic,1 Mark S. Singer,2 Zhi-Qiang Yang,6 Laura L. Kiessling,6 Steven D. Rosen,2 Susan J. Fisher123*

Trophoblast adhesion to the uterine wall is the requisite first step of implantation and, subsequently, placentation. At the maternal-fetal interface, we investigated the expression of selectin adhesion systems that enable leukocyte capture from the bloodstream. On the maternal side, human uterine epithelial cells up-regulated selectin oligosaccharide-based ligands during the window of receptivity. On the fetal side, human trophoblasts expressed L-selectin. This ligand-receptor system was functional, because beads coated with the selectin ligand 6-sulfo sLex bound to trophoblasts, and trophoblasts bound to ligand-expressing uterine luminal epithelium in tissue sections. These results suggest that trophoblast L-selectin mediates interactions with the uterus and that this adhesion mechanism may be critical to establishing human pregnancy.

Departments of 1 Stomatology, 2 Anatomy, and 3 Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA. 4 Nevada Center for Reproductive Medicine, Reno, NV 89509, USA. 5 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. 6 Departments of Chemistry and Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
*   To whom correspondence should be addressed. E-mail: sfisher{at}

The Differential Expression of MicroRNAs Between Implantation Sites and Interimplantation Sites in Early Pregnancy in Mice and Their Potential Functions.
Y. Geng, J. He, Y. Ding, X. Chen, Y. Zhou, S. Liu, X. Liu, and Y. Wang (2014)
Reproductive Sciences
   Abstract »    Full Text »    PDF »
Ulipristal Acetate: Critical Review About Endometrial and Ovulatory Effects in Emergency Contraception.
B. Mozzanega, S. Gizzo, S. Di Gangi, E. Cosmi, and G. B. Nardelli (2014)
Reproductive Sciences
   Abstract »    Full Text »    PDF »
Characterization of the Temporal and Spatial Expression of a Disintegrin and Metalloprotease 17 in the Human Endometrium and Fallopian Tube.
A. P. Jowicz, J. K. Brown, S. E. McDonald, J. L. V. Shaw, H. O. D. Critchley, and A. W. Horne (2013)
Reproductive Sciences 20, 1321-1326
   Abstract »    Full Text »    PDF »
MicroRNAs miR-30b, miR-30d, and miR-494 Regulate Human Endometrial Receptivity.
S. Altmae, J. A. Martinez-Conejero, F. J. Esteban, M. Ruiz-Alonso, A. Stavreus-Evers, J. A. Horcajadas, and A. Salumets (2013)
Reproductive Sciences 20, 308-317
   Abstract »    Full Text »    PDF »
The role of carbohydrate recognition during human sperm-egg binding.
G. F. Clark (2013)
Hum. Reprod. 28, 566-577
   Abstract »    Full Text »    PDF »
In Vivo Regulation of Steroid Hormones by the Chst10 Sulfotransferase in Mouse.
M. Suzuki-Anekoji, A. Suzuki, S.-W. Wu, K. Angata, K. K. Murai, K. Sugihara, T. O. Akama, K.-H. Khoo, J. Nakayama, M. N. Fukuda, et al. (2013)
J. Biol. Chem. 288, 5007-5016
   Abstract »    Full Text »    PDF »
In Vitro Evidences of Heparin's Effects on Embryo Implantation and Trophoblast Development.
C. Tersigni, R. Marana, A. Santamaria, R. Castellani, G. Scambia, and N. D. Simone (2012)
Reproductive Sciences 19, 454-462
   Abstract »    Full Text »    PDF »
Fucose, placental evolution and the glycocode.
J. D. Aplin and C. J. Jones (2012)
Glycobiology 22, 470-478
   Abstract »    Full Text »    PDF »
Identification of Mono- and Disulfated N-Acetyl-lactosaminyl Oligosaccharide Structures as Epitopes Specifically Recognized by Humanized Monoclonal Antibody HMOCC-1 Raised against Ovarian Cancer.
T. K. Shibata, F. Matsumura, P. Wang, S. Yu, C.-C. Chou, K.-H. Khoo, K. Kitayama, T. O. Akama, K. Sugihara, N. Kanayama, et al. (2012)
J. Biol. Chem. 287, 6592-6602
   Abstract »    Full Text »    PDF »
Trophoblast Stem Cells.
R. M. Roberts and S. J. Fisher (2011)
Biol Reprod 84, 412-421
   Abstract »    Full Text »    PDF »
Ephrin A1 induces intercellular dissociation in Ishikawa cells: possible implication of the Eph-ephrin A system in human embryo implantation.
H. Fujii, H. Fujiwara, A. Horie, Y. Sato, and I. Konishi (2011)
Hum. Reprod. 26, 299-306
   Abstract »    Full Text »    PDF »
Effects of cigarette smoking on reproduction.
C. Dechanet, T. Anahory, J. C. Mathieu Daude, X. Quantin, L. Reyftmann, S. Hamamah, B. Hedon, and H. Dechaud (2011)
Hum. Reprod. Update 17, 76-95
   Abstract »    Full Text »    PDF »
Macrophage-Derived LIF and IL1B Regulate Alpha(1,2)Fucosyltransferase 2 (Fut2) Expression in Mouse Uterine Epithelial Cells During Early Pregnancy.
M. J. Jasper, A. S. Care, B. Sullivan, W. V. Ingman, J. D. Aplin, and S. A. Robertson (2011)
Biol Reprod 84, 179-188
   Abstract »    Full Text »    PDF »
Early stages of implantation as revealed by an in vitro model.
H. Singh, L. Nardo, S. J. Kimber, and J. D. Aplin (2010)
Reproduction 139, 905-914
   Abstract »    Full Text »    PDF »
Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis.
J. J. Brosens, A. Hodgetts, F. Feroze-Zaidi, J. R. A. Sherwin, L. Fusi, M. S. Salker, J. Higham, G. L. Rose, T. Kajihara, S. L. Young, et al. (2010)
Mol. Hum. Reprod. 16, 273-285
   Abstract »    Full Text »    PDF »
Endometrial gene expression analysis at the time of embryo implantation in women with unexplained infertility.
S. Altmae, J.A. Martinez-Conejero, A. Salumets, C. Simon, J.A. Horcajadas, and A. Stavreus-Evers (2010)
Mol. Hum. Reprod. 16, 178-187
   Abstract »    Full Text »    PDF »
Altered glycosylation in peri-implantation phase endometrium in women with stages III and IV endometriosis.
D.L. Miller, C.J.P. Jones, J.D. Aplin, and L.G. Nardo (2010)
Hum. Reprod. 25, 406-411
   Abstract »    Full Text »    PDF »
L-Selectin ligands in human endometrium: comparison of fertile and infertile subjects.
L. Margarit, D. Gonzalez, P.D. Lewis, L. Hopkins, C. Davies, R.S. Conlan, L. Joels, and J.O. White (2009)
Hum. Reprod. 24, 2767-2777
   Abstract »    Full Text »    PDF »
Secreted Phosphoprotein 1 (SPP1, Osteopontin) Binds to Integrin Alphavbeta6 on Porcine Trophectoderm Cells and Integrin Alphavbeta3 on Uterine Luminal Epithelial Cells, and Promotes Trophectoderm Cell Adhesion and Migration.
D. W. Erikson, R. C. Burghardt, K. J. Bayless, and G. A. Johnson (2009)
Biol Reprod 81, 814-825
   Abstract »    Full Text »    PDF »
The Human Endometrium Expresses the Glycoprotein Mucin-1 and Shows Positive Correlation for Thomsen-Friedenreich Epitope Expression and Galectin-1 Binding.
U. Jeschke, H. Walzel, I. Mylonas, P. Papadopoulos, N. Shabani, C. Kuhn, S. Schulze, K. Friese, U. Karsten, D. Anz, et al. (2009)
Journal of Histochemistry & Cytochemistry 57, 871-881
   Abstract »    Full Text »    PDF »
Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment.
M. S. M. van Mourik, N. S. Macklon, and C. J. Heijnen (2009)
J. Leukoc. Biol. 85, 4-19
   Abstract »    Full Text »    PDF »
The potential role of heparin in assisted conception.
S. M. Nelson and I. A. Greer (2008)
Hum. Reprod. Update 14, 623-645
   Abstract »    Full Text »    PDF »
Lysophospholipid signaling in the function and pathology of the reproductive system.
X. Ye (2008)
Hum. Reprod. Update 14, 519-536
   Abstract »    Full Text »    PDF »
Expression and regulation of fucosyltransferase 4 in human endometrium.
A. P Ponnampalam and P. A W Rogers (2008)
Reproduction 136, 117-123
   Abstract »    Full Text »    PDF »
CX3CL1 and CCL14 Regulate Extracellular Matrix and Adhesion Molecules in the Trophoblast: Potential Roles in Human Embryo Implantation.
N. J Hannan and L. A Salamonsen (2008)
Biol Reprod 79, 58-65
   Abstract »    Full Text »    PDF »
Changing etiology of tubal pregnancy following IVF.
A. Revel, I. Ophir, M. Koler, H. Achache, and D. Prus (2008)
Hum. Reprod. 23, 1372-1376
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor--{alpha} Converting Enzyme in the Human Placenta Throughout Gestation.
T.-H. Hung, S.-F. Chen, C.-C. Hsieh, J.-J. Hsu, M.-J. Li, Y.-L. Yeh, and T.-T. Hsieh (2008)
Reproductive Sciences 15, 195-209
   Abstract »    PDF »
Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation.
H. Uchida, T. Maruyama, K. Ohta, M. Ono, T. Arase, M. Kagami, H. Oda, T. Kajitani, H. Asada, and Y. Yoshimura (2007)
Hum. Reprod. 22, 2615-2622
   Abstract »    Full Text »    PDF »
Decidual Stromal Cell Response to Paracrine Signals from the Trophoblast: Amplification of Immune and Angiogenic Modulators.
A.P. Hess, A.E. Hamilton, S. Talbi, C. Dosiou, M. Nyegaard, N. Nayak, O. Genbecev-Krtolica, P. Mavrogianis, K. Ferrer, J. Kruessel, et al. (2007)
Biol Reprod 76, 102-117
   Abstract »    Full Text »    PDF »
Endometrial receptivity markers, the journey to successful embryo implantation.
H. Achache and A. Revel (2006)
Hum. Reprod. Update 12, 731-746
   Abstract »    Full Text »    PDF »
The human endometrium as a fertility-determining factor.
T. Strowitzki, A. Germeyer, R. Popovici, and M. von Wolff (2006)
Hum. Reprod. Update 12, 617-630
   Abstract »    Full Text »    PDF »
Possible involvement of crosstalk cell-adhesion mechanism by endometrial CD26/dipeptidyl peptidase IV and embryonal fibronectin in human blastocyst implantation.
Y. Shimomura, H. Ando, K. Furugori, H. Kajiyama, M. Suzuki, A. Iwase, S. Mizutani, and F. Kikkawa (2006)
Mol. Hum. Reprod. 12, 491-495
   Abstract »    Full Text »    PDF »
The Chemokines, CX3CL1, CCL14, and CCL4, Promote Human Trophoblast Migration at the Feto-Maternal Interface.
N. J. Hannan, R. L. Jones, C. A. White, and L. A. Salamonsen (2006)
Biol Reprod 74, 896-904
   Abstract »    Full Text »    PDF »
Glycosylation dependent cell adhesion molecule 1-like protein and L-selectin expression in sheep interplacentomal and placentomal endometrium..
J. J Muniz, M. M Joyce, J. D Taylor II, J. R Burghardt, R. C Burghardt, and G. A Johnson (2006)
Reproduction 131, 751-761
   Abstract »    Full Text »    PDF »
Potential Selectin L Ligands Involved in Selective Recruitment of Peripheral Blood CD16(-) Natural Killer Cells into Human Endometrium.
T. Yamaguchi, K. Kitaya, N. Daikoku, T. Yasuo, S. Fushiki, and H. Honjo (2006)
Biol Reprod 74, 35-40
   Abstract »    Full Text »    PDF »
Embryonic implantation and leukocyte transendothelial migration: different processes with similar players?.
F. Dominguez, M. Yanez-Mo, F. Sanchez-Madrid, and C. Simon (2005)
FASEB J 19, 1056-1060
   Abstract »    Full Text »    PDF »
The Evolution of in Vitro Fertilization: Integration of Pharmacology, Technology, and Clinical Care.
E. C. Feinberg, J. G. Bromer, and W. H. Catherino (2005)
J. Pharmacol. Exp. Ther. 313, 935-942
   Abstract »    Full Text »    PDF »
Implantation mechanisms: insights from the sheep.
T. E Spencer, G. A Johnson, F. W Bazer, and R. C Burghardt (2004)
Reproduction 128, 657-668
   Abstract »    Full Text »    PDF »
Differential Expression of Genes in the Endometrium at Implantation: Upregulation of a Novel Member of the E2 Class of Ubiquitin-Conjugating Enzymes.
M. H. Melner, N. A. Ducharme, A. R. Brash, V. P. Winfrey, and G. E. Olson (2004)
Biol Reprod 70, 406-414
   Abstract »    Full Text »    PDF »
Coordinate Regulation of Lymphocyte-Endothelial Interactions by Pregnancy-Associated Hormones.
S. Chantakru, W.-C. Wang, M. van den Heuvel, S. Bashar, A. Simpson, Q. Chen, B. A. Croy, and S. S. Evans (2003)
J. Immunol. 171, 4011-4019
   Abstract »    Full Text »    PDF »
ADAM-17-independent shedding of L-selectin.
B. Walcheck, S. R. Alexander, C. A. St. Hill, and E. Matala (2003)
J. Leukoc. Biol. 74, 389-394
   Abstract »    Full Text »    PDF »
Regulation of Blastocyst Migration, Apposition, and Initial Adhesion by a Chemokine, Interferon {gamma}-inducible Protein 10 kDa (IP-10), during Early Gestation.
K. Nagaoka, H. Nojima, F. Watanabe, K.-T. Chang, R. K. Christenson, S. Sakai, and K. Imakawa (2003)
J. Biol. Chem. 278, 29048-29056
   Abstract »    Full Text »    PDF »
BMJ 326, 344
   Full Text »    PDF »
DEVELOPMENT: What Makes an Embryo Stick?.
A. T. Fazleabas and J. J. Kim (2003)
Science 299, 355-356
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882