Skip to main content
SpringerLink
Log in

sLeX/L-selectin mediates adhesion in vitro implantation model

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The complex implantation process is initiated by the recognition and adhesion between the embryo and uterine endometrial epithelium. The expression and interactions between the adhesive molecules from both fetal and maternal sides are crucial for the successful implantation. In this study, we aimed to investigate the expression and adhesive function of sLeX on the trophoblasts and L-selectin on uterine epithelial cells mediated the adhesion at the fetal–maternal interface, and to further explore whether this adhesion system could induce endometrial apoptosis, using in vitro implantation model consisting of the human trophoblast cell line (JAR) and human uterine epithelial cell line (RL95-2). The results showed that sLeX was expressed on JAR cells by indirect immunofluorescence staining. After transfection of JAR cells with fucosyltransferase VII (FUT7) which is the key enzyme for sLeX synthesis, the expression of FUT7 and sLeX synthesis were increased, and the percent adhesion of trophoblast cells to RL95-2 cell monolayer was significantly increased (P < 0.01). L-selectin was strongly expressed but not E- and P-selectin on epithelial RL95-2 cells by RT-PCR, Western blot. Blocking L-selectin with specific antibody or heparin pretreatment in RL95-2 cells inhibited the adhesion of JAR cells to RL95-2 cell monolayer. Furthermore, regulating the expression of sLeX on JAR cells or blocking L-selectin on RL95-2 cells could activate the apoptosis of uterine epithelial cells. These results suggest the sLeX/L-selectin adhesion system at fetal–maternal interface not only mediates the adhesion of embryo to uterine epithelium, but also effectively induces the apoptosis in uterine epithelium. The study supplies a molecular basis for the elucidation of the initial recognition and adhesion during embryo implantation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

sLeX:

Sialyl Lewis X

FUT7:

Fucosyltransferase VII

SNARF-1:

5-Chloromethy carboxyseminapthorhodofluor-1

DAPI:

4,6-Diamino-2-phenyl indole

TRITC:

Tetramethylrhodamine isothiocyanate

FITC:

Fluoresceinisothiocyanate

HRP:

Horseradish peroxidase

PE:

Phycoerythrin

FBS:

Fetal bovine serum

BSA:

Bovine serum albumin

ECL:

Enhanced chemiluminescence

References

  1. Guzeloglu-Kayisli O, Basar M, Arici A (2007) Basic aspects of implantation. Reprod Biomed Online 15:728–739

    Article  PubMed  CAS  Google Scholar 

  2. Makrigiannakis A, Minas V (2007) Mechanisms of implantation. Reprod Biomed Online 14:102–109

    Article  PubMed  CAS  Google Scholar 

  3. Aplin JD (1997) Adhesion molecules in implantation. Rev Reprod 2:84–93

    Article  PubMed  CAS  Google Scholar 

  4. Dey SK, Lim H, Das SK et al (2004) Molecular cues to implantation. Endocr Rev 25:341–373

    Article  PubMed  CAS  Google Scholar 

  5. Lai TH, Shih IeM, Vlahos N, Ho CL, Wallach E, Zhao Y (2005) Differential expression of L-selectin ligand in the endometrium during the menstrual cycle. Fertil Steril 83:1297–1302

    Article  PubMed  CAS  Google Scholar 

  6. Wang B, Sheng JZ, He RH, Qian YL, Jin F, Huang HF (2008) High expression of L-selectin ligand in secretory endometrium is associated with better endometrial receptivity and facilitates embryo implantation in human being. Am J Reprod Immunol 60:127–134

    Article  PubMed  Google Scholar 

  7. Läubli H, Stevenson JL, Varki A, Varki NM, Borsig L (2006) L-selectin facilitation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest. Cancer Res 66:1536–1542

    Article  PubMed  Google Scholar 

  8. Smith PL, Gersten KM, Petryniak B et al (1996) Expression of the alpha (1, 3) fucosyltransferase Fuc-TVII in lymphoid aggregate high endothelial venules correlates with expression of L-selectin ligands. J Biol Chem 271:8250–8259

    Article  PubMed  CAS  Google Scholar 

  9. Zhang Y, Liu S, Liu Y, Wang Z, Wang X, Yan Q (2009) Overexpression of fucosyltransferase VII (FUT7) promotes embryo adhesion and implantation. Fertil Steril 91:908–914

    Article  PubMed  CAS  Google Scholar 

  10. Liu S, Zhang Y, Liu Y, Qin H, Wang X, Yan Q (2008) FUT7 antisense sequence inhibits the expression of FUT7/sLeX and adhesion between embryonic and uterine cells. IUBMB Life 60:461–466

    Article  PubMed  CAS  Google Scholar 

  11. Uchimura K, Rosen SD (2006) Sulfated L-selectin ligands as a therapeutic target in chronic inflammation. Trends Immunol 27:559–565

    Article  PubMed  CAS  Google Scholar 

  12. Jackson LA, Drevets DA, Dong ZM, Greenfield RA, Murphy JW (2005) Levels of L-selectin (CD62L) on human leukocytes in disseminated cryptococcosis with and without associated HIV-1 infection. J Infect Dis 191:1361–1367

    Article  PubMed  CAS  Google Scholar 

  13. Kawashima H (2006) Roles of sulfated glycans in lymphocyte homing. Biol Pharm Bull 29:2343–2349

    Article  PubMed  CAS  Google Scholar 

  14. Resto VA, Burdick MM, Dagia NM, McCammon SD, Fennewald SM, Sackstein R (2008) L-selectin-mediated lymphocyte–cancer cell interactions under low fluid shear conditions. J Biol Chem 283:15816–15824

    Article  PubMed  CAS  Google Scholar 

  15. McEver RP (1997) Selectin–carbohydrate interactions during inflammation and metastasis. Glycoconj J 14:585–591

    Article  PubMed  CAS  Google Scholar 

  16. Genbacev OD, Prakobphol A, Foulk RA et al (2003) Trophoblast L-selectin-mediated adhesion at the maternal–fetal interface. Science 299:405–408

    Article  PubMed  CAS  Google Scholar 

  17. Fazleabas AT, Kim JJ (2003) What makes an embryo stick? Science 299:355–356

    Article  PubMed  CAS  Google Scholar 

  18. Galan A, O’Connor JE, Valbuena D et al (2000) The human blastocyst regulates endometrial epithelial apoptosis in embryonic adhesion. Biol Reprod 63:430–439

    PubMed  CAS  Google Scholar 

  19. Thie M, Denker HW (2002) In vitro studies on endometrial adhesiveness for trophoblast: cellular dynamics in uterine epithelial cells. Cells Tissues Organs 172:237–252

    Article  PubMed  Google Scholar 

  20. Tinel H, Denker HW, Thie M (2000) Calcium influx in human uterine epithelial RL95-2 cells triggers adhesiveness for trophoblast-like cells. Model studies on signalling events during embryo implantation. Mol Hum Reprod 6:1119–1130

    Article  PubMed  CAS  Google Scholar 

  21. Nelson SM, Greer IA (2008) The potential role of heparin in assisted conception. Hum Reprod Update 14:623–645

    Article  PubMed  CAS  Google Scholar 

  22. Stevenson JL, Varki A, Borsig L (2007) Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effects. Thromb Res 120:107–111

    Article  Google Scholar 

  23. Abrahams VM, Straszewski-Chavez SL, Guller S, Mor G (2004) First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod 10:55–63

    Article  PubMed  CAS  Google Scholar 

  24. Staun RE, Shalev E (2005) Human trophoblast function during the implantation process. Reprod Biol Endocrinol 20:56

    Article  Google Scholar 

  25. Achache H, Revel A (2006) Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update 12:731–746

    Article  PubMed  Google Scholar 

  26. Carson DD (2002) The glycobiology of implantation. Front Biosci 1:1535–1544

    Article  Google Scholar 

  27. Wang XQ, Zhu ZM (1998) Role for cell surface oligosaccharide in cell-cell recognition during implantation. Mol Hum Reprod 4:735–738

    PubMed  Google Scholar 

  28. Shamonki MI, Kligman I, Shamonki JM (2006) Immunohistochemical expression of endometrial L-selectin ligand is higher in donor egg recipients with embryonic implantation. Fertil Steril 86:1365–1375

    Article  PubMed  CAS  Google Scholar 

  29. Prakobphol A, Genbacev O, Gormley M, Kapidzic M, Fisher SJ (2006) A role for the L-selectin adhesion system in mediating cytotrophoblast emigration from the placenta. Dev Biol 298:107–117

    Article  PubMed  CAS  Google Scholar 

  30. Becker DJ, Lowe JB (2003) Fucose: biosynthesis and biological function in mammals. Glycobiology 13:41–53

    Article  Google Scholar 

  31. Taniguchi N, Honke K, Fukuda M (2002) Handbook of glycosyltransferases and related genes. In: Oriol R, Mollicone R, Narimatsu H (eds) Fucosyltransferases. Springer, Tokyo, pp 205–231

    Google Scholar 

  32. Zhang Q, Liu S, Zhu Z, Yan Q (2009) Regulating effect of LIF on the expression of FuT7: probe into the mechanism of sLe(x) in implantation. Mol Reprod Dev 76(8):692

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by National Natural Science Foundation of China Research Grant (30670465), Specialized Research Fund for the Doctoral Program of Higher Education of China (20060161001), and Fund for Creative Research Groups of Liaoning Province (2007T021).

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People’s Republic of China

    Shuai Liu, Xuesong Yang & Qiu Yan

  2. Central Laboratory, 1st Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China

    Yuejian Liu

  3. Department of Dermatology and Pediatrics, Northwestern University’s Feinberg School of Medicine, Chicago, IL, USA

    Xiaoqi Wang

Authors
  1. Shuai Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuesong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuejian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoqi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qiu Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qiu Yan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, S., Yang, X., Liu, Y. et al. sLeX/L-selectin mediates adhesion in vitro implantation model. Mol Cell Biochem 350, 185–192 (2011). https://doi.org/10.1007/s11010-010-0697-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-010-0697-x

Keywords

Search

Navigation