Recent Molecular Approaches to Elucidate the Mechanism of Embryo Implantation: Trophinin, Bystin, and Tastin as Molecules Involved in the Initial Attachment of Blastocysts to the Uterus in Humans

ABSTRACT

Elucidation of the implantation mechanism in humans at the molecular level has been difficult because of methodological restrictions. Instead of using human materials during the implantation period, two human tumor cell lines that respectively mimic the biological behaviors of a blastocyst and uterine luminal epithelial cells were utilized successfully to identify three novel adhesion molecules named trophinin, bystin, and tastin. Trophinin is a membrane protein strongly expressed both on the apical surface of the trophectoderm of a simian blastocyst and at a putative implantation site of the human endometrium. Bystin and tastin are cytoplasmic proteins that associate with trophinin by presumably forming an active adhesion machinery. The expression patterns of these molecules are suggestive of their involvement in the initial blastocyst attachment to the uterus as well as in the subsequent placental development. Future perspectives in molecular implantation research are also discussed in relation to breakthroughs in assisted reproduction.

KEYWORD

bystin - tastin

REFERENCES

• 1 Kaufman M H. The origin, properties and fate of trophoblast in the mouse. In: Loke YW, Whyte A, eds. Biology of Trophoblast New York: Elsevier Scientific 1985: 23-68
• 2 Cross J C, Werb Z, Fisher S J. Implantation and the placenta: key pieces of the development puzzle.  Science . 1994;  266 1508-1518
• 3 Enders A C, Chavez D J, Schlafke S. Comparison of implantation in utero and in vitro. In: Glasser SR, Bullock DW, eds. Cellular and Molecular Aspects of Implantation New York: Plenum 1981: 365-382
• 4 Ringler G E, Strauss III F J. Recent advances in understanding the process of implantation.  Curr Opin Cell Biol . 1990;  2 703-708
• 5 Aplin D J. Implantation, trophoblast differentiation and haemochorial placentation: mechanistic evidence in vivo and in vitro.  J Cell Sci . 1991;  99 681-692
• 6 Denker H W. Trophoblast-endometrial interactions at embryo implantation: a cell biological paradox. In: Denker HW, Aplin JD, eds. Trophoblast Invasion and Endometrial Receptivity: Novel Aspects of the Cell Biology of Embryo Implantation New York: Plenum Medical Book Corp 1990: 3-29
• 7 Kliman H J, Coutifaris C, Feinberg R F, Strauss J F, Haimowitz J E. Implantation: in vitro models utilizing human tissues. In: Yoshinaga K, ed. Blastocyst Implantation Boston: Adams 1989: 83-91
• 8 Farach M C, Tang J P, Decker G L, Carson D D. Heparin/heparan sulfate is involved in attachment and spreading of mouse embryos in vitro.  Dev Biol . 1987;  123 401-410
• 9 Rohde L H, Carson D D. Heparin-like glycosaminoglycans participate in binding of a human trophoblastic cell line (JAR) to a human uterine epithelial cell line (RL95).  J Cell Physiol . 1993;  155 185-196
• 10 Sutherland A E, Calario P G, Damsky C H. Expression and function of cell surface extracellular matrix receptors in mouse blastocyst attachment and outgrowth.  J Cell Biol . 1988;  106 1331-1348
• 11 Fukuda M N, Sato T, Nakayama J. Trophinin and tastin, a novel cell adhesion molecule complex with potential involvement in embryo implantation.  Genes Dev . 1995;  9 1199-1210
• 12 John N J, Linke M, Denker H-W. Quantification of human choriocarcinoma spheroid attachment to uterine epithelial cells monolayers.  In Vitro Cell Dev Biol . 1993;  29A 461-468
• 13 Ducibella T, Anderson D, Aalberg J, DeWolf W C. Cell surface polarization, tight junctions and eccentric inner cells characterize human teratocarcinoma embryoid bodies.  Dev Biol . 1982;  94 197-205
• 14 Izhar M, Siebert P D, Oshima R G, DeWolf W C, Fukuda M N. Trophoblastic differentiation of human teratocarcinoma cell line HT-T.  Dev Biol . 1986;  116 510-518
• 15 Ishiwata I, Nozawa S, Inoue T, Okumura H. Development and characterization of established cell lines from primary and metastatic regions of human endometrial carcinomas.  Cancer Res . 1977;  37 1777-1785
• 16 Andrew P W, Bronson D L, Benham F, Strickland S, Knowles B B. A comparative study of eight cell lines derived from human testicular teratocarcinoma.  Int J Cancer . 1980;  26 269-284
• 17 Andrews P W, Goodfellow P N, Damajanov I. Human teratocarcinoma cells in culture.  Cancer Surv . 1983;  2 41-73
• 18 Lindenberg S, Hyttel P, Lenz S, Holmes P V. Ultrastructure of the early human implantation in vitro.  Hum Reprod . 1986;  1 533-538
• 19 Knoth M, Larsen J F. Ultrastructure of a human implantation site.  Acta Obstet Gynecol Scand . 1972;  51 385-393
• 20 Suzuki N, Zara J, Sato T. A cytoplasmic protein, bystin, interacts with trophinin, tastin and cytokeratin, and may be involved in trophinin-mediated cell adhesion between trophoblast and endometrial epithelial cells.  Proc Natl Acad Sci U S A . 1998;  95 5027-5032
• 21 Suzuki N, Nakayama J, Shih I-M, Aoki D, Nozawa S, Fukuda M N. Expression of trophinin, tastin, and bystin by trophoblast and endometrial cells in human placenta.  Biol Reprod . 1999;  60 621-627
• 22 Oda T, Aoki R, Yoshimura Y. Role of corpus luteum function in embryo implantation.  Horm Res . 1992;  37(suppl 1) 75-78
• 23 Bergh P A, Navot D. The impact of embryonic development and endometrial maturity on the timing of implantation.  Fertil Steril . 1992;  58 537-542
• 24 Weiden R MF, Helmerhorst F M, Keirse M N C J. Influence of prostaglandins and platelet activating factor on implantation.  Hum Reprod . 1988;  3 993-998
• 25 Duc-Goiran P, Mignot T M, Bourgeois C, Ferre F. Embryo-maternal interactions at the implantation site: a delicate equilibrium.  Euro J Obstet Gynecol Reprod Biol . 1999;  83 85-100