Unterschiede in der Trophoblastinvasion bei der Tubar- und Intrauteringravidität

Zusammenfassung

Vergleicht man die Trophoblastinvasion bei der Extrauteringravidität (EUG) mit der Intrauteringravidität (IUG), so lassen sich Gemeinsamkeiten mit der IUG finden bezüglich der Expression des Human leukocyte antigen (HLA)-G in den extravillösen Trophoblastzellen und der beim Umbau der Extrazellulärmatrix beteiligten Proteasen (MT1-MMP, MT2-MMP, MMP-1, TIMP-2), die ebenfalls in den extravillösen Trophoblastzellen lokalisiert sind. Auch die bei der Implantation beteiligten Zytokine sind vergleichbar (LIF, TGFβ, Interferone, EGF). Jedoch fehlen die für die IUG typischen NK-Zellen.

Bei der Tubargravidität kann zwischen Tubarabort und vitaler Tubargravidität unterschieden werden. Dabei zeigt die vitale Tubargravidität im Gegensatz zum Tubarabort eine verstärkte Invasivität gegenüber der IUG. Kennzeichnend hierfür ist, dass die für die IUG typische strikte Trennung zwischen dem proliferativen und dem invasiven Phänotyp der Trophoblastzellen aufgehoben ist. Hierdurch kommt es zu einer Überlappung zwischen Proliferations- und Invasionszone mit entsprechend früher apolarer Matrixsekretion und vorzeitigem Switch hin zur Expression invasionsassoziierter Integrine.

Abstract

If trophoblast invasion in ectopic pregnancy is compared with intrauterine pregnancy similarities can be observed concerning the expression of human leukocyte antigen (HLA)-G in extravillous trophoblast cells and concerning the proteases which are involved in the remodelling of the extracellular matrix (MT1-MMP, MT2-MMP, MMP-1, TIMP-2) and which are also located in extravillous trophoblast cells. The same is true for the cytokines involved in implantation (LIF, TGFβ, interferons, EGF). However, NK cells which are typical for intrauterine pregnancy are absent.

Ectopic pregnancies can be divided into viable tubal pregnancies and tubal abortions. In viable tubal pregnancies trophoblast invasion is enhanced compared to intrauterine pregnancy and to tubal abortion. It is characteristic for those cases that the strict discrimination between the proliferative and the invasive phenotype of trophoblast typical for intrauterine pregnancies is abolished. So proliferative and invasive zone are overlapping with earlier apolar matrix secretion and expedited switch towards invasion-associated integrin expression.

Schlüsselwörter

Trophoblastinvasion - Tubargravidität - Intrauteringravidität

Key words

Trophoblast invasion - Tubal pregnancy - Intrauterine pregnancy

Literatur

• 1 Lala P K, Hamilton G S. Growth factors, proteases and protease inhibitors in the maternal-fetal dialogue.  Placenta. 1996;  17 545-555
• 2 Kokawa K, Shikone T, Nakano R. Apoptosis in human chorionic villi and decidua in normal and ectopic pregnancy.  Mol Hum Reprod. 1998;  4 87-91
• 3 Marx L, Arck P, Kapp M, Kieslich C, Dietl J. Leukocyte populations, hormone receptors and apoptosis in eutopic and ectopic first trimester human pregnancies.  Hum Reprod. 1999;  14 1111-1117
• 4 Hucke J. Extrauterine Schwangerschaft.  Gynäkologe. 1997;  30 875-887 958-968
• 5 Kemp B, Funk A, Hauptmann S, Leeners B, Rath W. Dopplersonographische Vitalitätskriterien bei klinisch stabiler Extrauteringravidität - eine Entscheidungshilfe für die Therapie.  Geburtsh Frauenheilk. 1998;  58 88-92
• 6 Kemp B, Kertschanska S, Handt S, Funk A, Kaufmann P, Rath W. Different placentation patterns in viable compared with non-viable tubal pregnancy suggest a divergent clinical management.  Am J Obstet Gynecol. 1999;  181 615-620
• 7 Benirschke K, Kaufmann P. Pathology of the Human Placenta. 4. Aufl. New York; Springer 2000
• 8 Kaufmann P, Castellucci M. Extravillous trophoblast in the human placenta - a review.  Trophoblast Res. 1997;  10 21-65
• 9 Kemp B, Kertschanska S, Kadyrov M, Rath W, Kaufmann P, Huppertz B. Invasive depth of extravillous trophoblast correlates with cellular phenotype - a comparison of intra- and extrauterine implantation sites.  Histochem Cell Biol. 2002; 
• 10 Goldmann-Wohl D S, Ariel I, Greenfield C, Hanoch J, Yagel S. HLA-G expression in extravillous trophoblasts is an intrinsic property of cell differentiation: a lesson learned from ectopic pregnancies.  Mol Hum Reprod. 2000;  6 535-540
• 11 Proll J, Bensussan A, Goffin F, Foidart J M, Berrebi A, Le Bouteiller P. Tubal versus uterine placentation: similar HLA-G expressing extravillous cytotrophoblast invasion but different maternal leukocyte recruitment.  Tissue Antigens. 2000;  56 479-491
• 12 Earl U, Wells M, Bulmer J N. The expression of major histocompatibility complex antigens by trophoblast in ectopic tubal pregnancy.  J Reprod Immunol. 1985;  8 13-24
• 13 Akiyama S K, Olden K, Yamada K M. Fibronectin and integrins in invasion and metastasis.  Cancer Metastasis Rev. 1995;  14 173-189
• 14 Menzin A W, Loret de Mola J R, Bilker W B, Wheeler J E, Rubin S C, Feinberg R F. Identification of oncofetal fibronectin in patients with advanced epithelial ovarian cancer: detection in ascitic fluid and localization to primary sites and metastatic implants.  Cancer. 1998;  82 152-158
• 15 Damsky C H, Fitzgerald M L, Fisher S J. Distribution patterns of extracellular matrix components and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo.  J Clin Invest. 1992;  89 210-222
• 16 Damsky C H, Librach D, Lim K H, Fitzgerald M L, McMaster M T, Janatpour M, Zhou Y, Logan S K, Fisher S J. Integrin switching regulates normal trophoblast invasion.  Development. 1994;  120 3657-3666
• 17 Huppertz B, Kertschanska S, Frank H G, Gaus G, Funayama H, Kaufmann P. Extracellular matrix components of the placental extravillous trophoblast: immunocytochemistry and ultrastructural distribution.  Histochem Cell Biol. 1996;  106 291-301
• 18 Bjorn S F, Hastrup N, Lund L R, Dano K, Larsen J F, Pyke C. Co-ordinated expression of MMP-2 and its putative activator, MT1-MMP, in human placentation.  Mol Hum Reprod. 1997;  3 713-723
• 19 Huppertz B, Kertschanska S, Demir A Y, Frank H G, Kaufmann P. Immunohistochemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta.  Cell Tissue Res. 1998 b;  291 133-148
• 20 Pierleoni C, Samuelsen G B, Graem N, Ronne E, Nielsen B S, Kaufmann P, Castellucci M. Immunohistochemical identification of the receptor for urokinase plasminogen activator associated with fibrin deposition in normal and ectopic human placenta.  Placenta. 1998;  19 501-508
• 21 Floridon C, Nielsen O, Holund B, Sunde L, Westergaard J G, Thomsen S G, Teisner B. Localization and significance of urokinase plasminogen activator and its receptor in placental tissue from intrauterine, ectopic and molar pregnancies.  Placenta. 1999;  20 711-721
• 22 Bjorn S F, Hastrup N, Larsen J F, Lund L R, Pyke C. Messenger RNA for membrane-type 2 matrix metalloproteinase, MT2-MMP, is expressed in human placenta of first trimester.  Placenta. 2000;  21 170-176
• 23 Kucera E, Tangl S, Klem I, Konig F, Grosschmidt K, Kainz C, Sliutz G. Immunohistochemical expression of matrix metalloproteinases 1 and 2 (MMP-1 and MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in ruptured and non-ruptured tubal ectopic pregnancies.  Wien Klin Wochenschr. 2000;  112 749-753
• 24 Von Rango U, Classen-Linke I, Kertschanska S, Kemp B, Beier H M. Effects of trophoblast invasion on the distribution of leukocytes in uterine and tubal implantation sites.  Fertil Steril. 2001;  76 116-124
• 25 Vassiliadou N, Bulmer J N. Characterization of tubal and decidual leukocyte populations in ectopic pregnancy: evidence that endometrial granulated lymphocytes are absent from the tubal implantation site.  Fertil Steril. 1998;  69 760-767
• 26 Maruyama T, Makino T, Sugi T. Flow-cytometric analysis of immune cell populations in the human decidua from various types of first trimester human pregnancy.  Hum Immunol. 1992;  4 212-218
• 27 Keltz M D, Attar E, Buradagunta S, Olive D L, Kliman H J, Arici A. Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in the human fallopian tube.  Am J Obstet Gynecol. 1996;  175 1611-1619
• 28 Selick C E, Horowitz G M, Gratch M, Scott R T, Navot D, Hofmann G E. Immunohistochemical localization of transforming growth factor-beta in human implantation sites.  J Clin Endocrinol Metab. 1994;  78 592-596
• 29 Bulmer J N, Thrower S, Wells M. Expression of epidermal growth factor receptor and transferrin receptor by human trophoblast populations.  Am J Reprod Immunol. 1989;  21 87-93
• 30 Bulmer J N, Morrison L, Johnson P M, Meager A. Immunohistochemical localization of interferons in human placental tissues in normal, ectopic, and molar pregnancy.  Am J Reprod Immunol. 1990;  22 109-116
• 31 Kucera E, Konig F, Tangl S, Grosschmidt K, Kainz C, Sliutz G. Bcl-2 expression as a novel immunohistochemical marker for ruptured tubal ectopic pregnancy.  Hum Reprod. 2001;  16 1286-1290