Subscribe to RSS
DOI: 10.1055/s-2005-864115
Stimulierung der hCG-, Estrogen- und Progesteronproduktion in isolierten Trophoblastzellen durch Glycodelin A bzw. seine N-Glycane
Stimulation of hCG, Estrogen and Progesterone Production in Isolated Trophoblast Cells by Glycodelin A or its N-GlycansPublication History
Eingereicht: 11.11.2004
Angenommen nach Überarbeitung: 8.2.2005
Publication Date:
26 April 2005 (online)

Zusammenfassung
Fragestellung: Das immunsuppressive Plazentaprotein Glycodelin A (GdA) wird in hohen Konzentrationen im ersten Trimester der Schwangerschaft vom sekretorischen Endometrium und der Decidua sezerniert. Der Anteil von GdA an der durch die Decidua freigesetzten Proteinmenge beträgt in dieser Zeit 10 %. GdA besitzt ungewöhliche Kohlenhydratstrukturen, zu denen insbesondere fukosylierte LacdiNAc-Strukturen gehören. In der vorliegenden Studie beschreiben wir die Wirkung von GdA bzw. seiner N-Glycane auf die hCG-, Estogen- und Progesteron-Freisetzung von Trophoblastzellen in vitro. Material und Methodik: Die Isolierung von Trophoblastzellen erfolgte aus zum Termin geborener Plazenta durch Fragmentierung einzelner Kotyledonen und anschließendem Verdau mit Hilfe von Trypsin/DNAse. Trophoblastzellen wurden mit unterschiedlichen GdA-Glycanen inkubiert. Die Produktion von hCG, Estrogen und Progesteron wurde nach 24 und 48 Stunden gemessen. Ergebnisse: Mit GdA bzw. GdA-Glycanen versetzte Trophoblastzellen weisen in vitro eine erhöhte hCG-, Estrogen- und Progesteron-Freisetzung im Vergleich zu unbehandelten Zellen auf. Schlussfolgerung: Progesteron, Estrogen und hCG sind „Marker” für den Differenzierungsprozess von Trophoblastzellen. Das mütterliche Protein Glycodelin A und insbesondere seine Kohlenhydratmoleküle scheinen fetale Trophoblastzellen in der Differenzierung zu stimulieren.
Abstract
The immunosuppressive protein glycodelin A (GdA) is secreted by decidual tissue in high rates in the first trimester of pregnancy. GdA forms about 10 % of the total protein amount released by the decidua in the first trimester of pregnancy and has a unique glycosylation including fucosylated LacdiNAc structures. The purpose of this study was to investigate the effect of glycodelin A and its N-glycans on hCG, estrogen and progesterone release by cytotrophoblasts in vitro. Trophoblast cells were isolated from human term placenta by fragmentation of villous tissue. Trophoblast cells fuse in vitro to syncytiotrophoblast cells. Trophoblast cells were incubated with GdA and various glycans of GdA. The production of hCG and progesterone was measured after 24 and 48 hours. The production of hCG, estrogen and progesterone was increased in GdA and glycan-treated cell cultures as compared to untreated trophoblast cell cultures. Conclusion: HCG, estrogen and progesterone are markers for the differentiation process of cytotrophoblast cells. The results suggest that GdA with its distinct glycosylation modulates the differentation of trophoblasts.
Schlüsselwörter
Glycodelin A - hCG - Progesteron - Trophoblastzellen - Kohlenhydratstrukturen
Key words
Glycodelin A - hCG - estrogen - progesterone - trophoblast cells - carbohydrates
Literatur
- 1 Bohn H, Kraus W, Winckler W. New soluble placental tissue proteins: their isolation, characterization, localization and quantification. Placenta. 1982; Suppl 4 67
- 2 Boime I. Human placental hormone production is linked to the stage of trophoblast differentiation. Tropho Res. 1991; 5 57
- 3 Bolton A E, Pockley A G, Clough K J, Mowles E A, Stoker R J, Westwood O M, Chapman M G. Identification of placental protein 14 as an immunosuppressive factor in human reproduction. Lancet. 1987; 1 593
- 4 Bukovsky A, Cekanova M, Caudle M R, Wimalasena J, Foster J S, Henley D C, Elder R F. Expression and localization of estrogen receptor-alpha protein in normal and abnormal term placentae and stimulation of trophoblast differentiation by estradiol. Reprod Biol Endocrinol. 2003; 1 13
- 5 Dell A, Morris H R, Easton R L, Panico M, Patankar M, Oehniger S, Koistinen R, Koistinen H, Seppala M, Clark G F. Structural analysis of the oligosaccharides derived from glycodelin, a human glycoprotein with potent immunosuppressive and contraceptive activities. J Biol Chem. 1995; 270 24 116
- 6 Grinnell B W, Hermann R B, Yan S B. Human protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide. Glycobiology. 1994; 4 221
- 7 Hokke C H, van den Eijnden D H. Enzyme-assisted synthesis of Asn-linked diantennary oligosaccharides occurring on glycodelin A. Carbohydr Res. 1997; 305 463
- 8 Jeschke U, Briese V, Richter D, Kunkel S. [Stimulation trials of trophoblast cells in vitro using PP14]. Z Geburtshilfe Neonatol. 1996; 200 199
- 9 Jeschke U, Briese V, Richter D, Kunkel S, Walzel H, Friese K. Neue Ergebnisse zur hCG-Regulation in der Plazenta. Geburtshilfe Frauenheilkd. 1997; 57 681
- 10 Jeschke U, Gundel G, Muller H, Richter D U, Streu A, Briese V, Mylonas I, Friese K, Unverzagt C. N-glycans of human amniotic fluid transferrin stimulate progesterone production in human first trimester trophoblast cells in vitro. J Perinat Med. 2004; 32 248
- 11 Jeschke U, Mylonas I, Richter D U, Streu A, Muller H, Briese V, Friese K. Human Amniotic Fluid Glycoproteins Expressing Sialyl Lewis Carbohydrate Antigens Stimulate Progesterone Production in Human Trophoblasts in vitro. Gynecol Obstet Invest. 2004; 58 207
- 12 Jeschke U, Richter D U, Walzel H, Bergemann C, Mylonas I, Sharma S, Keil C, Briese V, Friese K. Stimulation of hCG and inhibition of hPL in isolated human trophoblast cells in vitro by glycodelin A. Arch Gynecol Obstet. 2003; 268 162
- 13 Jeschke U, Wang X, Briese V, Friese K, Stahn R. Glycodelin and amniotic fluid transferrin as inhibitors of E-selectin-mediated cell adhesion. Histochem Cell Biol. 2003; 119 345
- 14 Julkunen M, Apter D, Seppala M, Stenman U H, Bohn H. Serum levels of placental protein 14 reflect ovulation in nonconceptional menstrual cycles. Fertil Steril. 1986; 45 47
- 15 Julkunen M, Rutanen E M, Koskimies A, Ranta T, Bohn H, Seppala M. Distribution of placental protein 14 in tissues and body fluids during pregnancy. Br J Obstet Gynaecol. 1985; 92 1145
- 16 Julkunen M, Seppala M, Janne O A. Complete amino acid sequence of human placental protein 14: a progesterone-regulated uterine protein homologous to beta-lactoglobulins. Proc Natl Acad Sci USA. 1988; 85 8845
- 17 Julkunen M, Seppala M, Janne O A. Molecular cloning of complementary DNAs for two human endometrial proteins and cellular localization of their messenger RNAs. Ann N Y Acad Sci. 1991; 626 284
- 18 Kliman H J, Nestler J E, Sermasi E, Sanger J M, Strauss J F, 3rd . Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae. Endocrinology. 1986; 118 1567
- 19 Morris H R, Dell A, Easton R L, Panico M, Koistinen H, Koistinen R, Oehninger S, Patankar M S, Seppala M, Clark G F. Gender-specific glycosylation of human glycodelin affects its contraceptive activity. J Biol Chem. 1996; 271 32 159
- 20 Morrow D M, Xiong N, Getty R R, Ratajczak M Z, Morgan D, Seppala M, Riittinen L, Gewirtz A M, Tykocinski M L. Hematopoietic placental protein 14. An immunosuppressive factor in cells of the megakaryocytic lineage. Am J Pathol. 1994; 145 1485
- 21 Mylonas I, Speer R, Makovitzky J, Richter D U, Briese V, Jeschke U, Friese K. Immunohistochemical analysis of steroid receptors and glycodelin A (PP14) in isolated glandular epithelial cells of normal human endometrium. Histochem Cell Biol. 2000; 114 405
- 22 Okamoto N, Uchida A, Takakura K, Kariya Y, Kanzaki H, Riittinen L, Koistinen R, Seppala M, Mori T. Suppression by human placental protein 14 of natural killer cell activity. Am J Reprod Immunol. 1991; 26 137
- 23 Pockley A G, Barratt C L, Bolton A E. Placental protein 14 (PP14) content and immunosuppressive activity of human cervical mucus. Symp Soc Exp Biol. 1989; 43 317
- 24 Pockley A G, Bolton A E. Placental protein 14 (PP14) inhibits the synthesis of interleukin-2 and the release of soluble interleukin-2 receptors from phytohaemagglutinin-stimulated lymphocytes. Clin Exp Immunol. 1989; 77 252
- 25 Pockley A G, Bolton A E. The effect of human placental protein 14 (PP14) on the production of interleukin-1 from mitogenically stimulated mononuclear cell cultures. Immunology. 1990; 69 277
- 26 Powell L D, Jain R K, Matta K L, Sabesan S, Varki A. Characterization of sialyloligosaccharide binding by recombinant soluble and native cell-associated CD22. Evidence for a minimal structural recognition motif and the potential importance of multisite binding. J Biol Chem. 1995; 270 7523
- 27 Rachmilewitz J, Riely G J, Huang J H, Chen A, Tykocinski M L. A rheostatic mechanism for T-cell inhibition based on elevation of activation thresholds. Blood. 2001; 98 3727
- 28 Rachmilewitz J, Riely G J, Tykocinski M L. Placental protein 14 functions as a direct T-cell inhibitor. Cell Immunol. 1999; 191 26
- 29 Reimer T, Koczan D, Briese V, Friese K, Richter D, Thiesen H J, Jeschke U. Absolute quantification of human chorionic gonadotropin-beta mRNA with TaqMan detection. 4. Mol Biotechnol. 2000; 14 47
- 30 Riittinen L, Julkunen M, Seppala M, Koistinen R, Huhtala M L. Purification and characterization of endometrial protein PP14 from mid-trimester amniotic fluid. Clin Chim Acta. 1989; 184 19
- 31 Seppala M, Koistinen R, Rutanen E M. Uterine endocrinology and paracrinology: insulin-like growth factor binding protein-1 and placental protein 14 revisited. Hum Reprod. 1994; 9 917
- 32 Streu A, Jeschke U, Richter D U, Muller H, Briese V, Friese K. [Human amniotic fluid transferrin stimulates progesterone production by human trophoblast cells in vitro]. Zentralbl Gynakol. 2000; 122 407
- 33 Vaisse C, Atger M, Potier B, Milgrom E. Human placental protein 14 gene: sequence and characterization of a short duplication. DNA Cell Biol. 1990; 9 401
- 34 Westwood O M, Chapman M G, Totty N, Philp R, Bolton A E, Lazarus N R. N-terminal sequence analysis of human placental protein 14, purified in high yield from decidual cytosol. J Reprod Fertil. 1988; 82 493
PD Dr. Udo Jeschke
Ludwig Maximilians Universität München
I. Frauenklinik-Innenstadt
Maistrasse 11
80337 München
Phone: 089 5160 4266
Fax: 089 5160 4916
Email: udo.jeschke@med.uni-muenchen.de