Abstract
The distribution of mRNAs and antigens of tissue type (t) and urokinase type (u) plasminogen activators (PA) plus their corresponding inhibitors, type-1 (PAI-1) and type-2 (PAI-2) were studied in human and rhesus monkey placentae by in situ hybridisation and immunocytochemistry. Specific monkey cRNA and antibodies against human tPA, uPA, PAI-1 and PAI-2 were used as probes. The following results were obtained. (1) All the molecules tPA, uPA, PAI-1 and PAI-2 and their mRNAs were identified in the majority of the extravillous cytotrophoblast cells of the decidual layer between Rohr's and Nitabuch's striae and in cytotrophoblast cells of the chorionic plate, basal plate, intercotyledonary septae and cytotrophoblast cells of the chorionic villous tree. (2) Expression of uPA and PAI-2 was noted in villous trophoblast whereas tPA and PAI-1 were mainly concentrated where detachment from maternal tissue occurs. (3) No expression of tPA, uPA, PAI-1 and PAI-2 was observed in the basal plate endometrial stromal cells, chorionic plate connective tissue cells, septal endometrial stromal cells or villous core mesenchyme. (4) The distribution of probes observed following in situ hybridisation is generally consistent with the immunofluorescence pattern of the corresponding antigens and no significant interspecies differences were noted. It is possible that both decidual and extravillous trophoblast cells of placentae of human and rhesus monkey are capable of producing tPA, uPA, PAI-1 and PAI-2 to differing extents. Coordinated expression of these genes in the tissue may play an essential role in the maintenance of normal placentation and parturition. The differences in distribution we observed are consistent with the suggestion that coordinated expression of tPA and its inhibitor PAI-1 may play a key role in fibrinolytic activity in the early stages of placentation and separation of placenta from maternal tissue at term. On the other hand, uPA with its inhibitor PAI-2 appears mainly to play a role in degradation of trophoblast cell-associated extracellular matrix, and thus may be of greatest importance during early stages of placentation.
Keywords: Pregnancy, placentation, trophoblast
Full Text
The Full Text of this article is available as a PDF (780.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blasi F., Vassalli J. D., Danø K. Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors. J Cell Biol. 1987 Apr;104(4):801–804. doi: 10.1083/jcb.104.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradbury F. M., Ockleford C. D. A confocal and conventional epifluorescence microscope study of the intermediate filaments in chorionic villi. J Anat. 1990 Apr;169:173–187. [PMC free article] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Estellés A., Gilabert J., Aznar J., Loskutoff D. J., Schleef R. R. Changes in the plasma levels of type 1 and type 2 plasminogen activator inhibitors in normal pregnancy and in patients with severe preeclampsia. Blood. 1989 Sep;74(4):1332–1338. [PubMed] [Google Scholar]
- Estellés A., Gilabert J., Keeton M., Eguchi Y., Aznar J., Grancha S., Espña F., Loskutoff D. J., Schleef R. R. Altered expression of plasminogen activator inhibitor type 1 in placentas from pregnant women with preeclampsia and/or intrauterine fetal growth retardation. Blood. 1994 Jul 1;84(1):143–150. [PubMed] [Google Scholar]
- Fazleabas A. T., Everly S. L., Lottenberg R. Immunological and molecular characterization of plasminogen activator inhibitors 1 and 2 in baboon (Papio anubis) placental tissues. Biol Reprod. 1991 Jul;45(1):49–56. doi: 10.1095/biolreprod45.1.49. [DOI] [PubMed] [Google Scholar]
- Feinberg R. F., Kao L. C., Haimowitz J. E., Queenan J. T., Jr, Wun T. C., Strauss J. F., 3rd, Kliman H. J. Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI-1 is an immunocytochemical marker of invading trophoblasts. Lab Invest. 1989 Jul;61(1):20–26. [PubMed] [Google Scholar]
- Feinberg R. F., Kliman H. J., Lockwood C. J. Is oncofetal fibronectin a trophoblast glue for human implantation? Am J Pathol. 1991 Mar;138(3):537–543. [PMC free article] [PubMed] [Google Scholar]
- Fisher S. J., Cui T. Y., Zhang L., Hartman L., Grahl K., Zhang G. Y., Tarpey J., Damsky C. H. Adhesive and degradative properties of human placental cytotrophoblast cells in vitro. J Cell Biol. 1989 Aug;109(2):891–902. doi: 10.1083/jcb.109.2.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fisher S. J., Leitch M. S., Kantor M. S., Basbaum C. B., Kramer R. H. Degradation of extracellular matrix by the trophoblastic cells of first-trimester human placentas. J Cell Biochem. 1985;27(1):31–41. doi: 10.1002/jcb.240270105. [DOI] [PubMed] [Google Scholar]
- Frank H. G., Malekzadeh F., Kertschanska S., Crescimanno C., Castellucci M., Lang I., Desoye G., Kaufmann P. Immunohistochemistry of two different types of placental fibrinoid. Acta Anat (Basel) 1994;150(1):55–68. doi: 10.1159/000147602. [DOI] [PubMed] [Google Scholar]
- Gow L., Campbell D. M., Ogston D. The fibrinolytic system in pre-eclampsia. J Clin Pathol. 1984 Jan;37(1):56–58. doi: 10.1136/jcp.37.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HAMILTON W. J., BOYD J. D. Development of the human placenta in the first three months of gestation. J Anat. 1960 Jul;94:297–328. [PMC free article] [PubMed] [Google Scholar]
- Hofmann G. E., Glatstein I., Schatz F., Heller D., Deligdisch L. Immunohistochemical localization of urokinase-type plasminogen activator and the plasminogen activator inhibitors 1 and 2 in early human implantation sites. Am J Obstet Gynecol. 1994 Feb;170(2):671–676. doi: 10.1016/s0002-9378(94)70246-2. [DOI] [PubMed] [Google Scholar]
- Jonasson A., Larsson B., Lecander I., Astedt B. Placental and decidual u-PA, t-PA, PAI-1 and PAI-2 concentrations, as affected by cervical dilatation with laminaria tents or Hegar dilators. Thromb Res. 1989 Jan 15;53(2):91–97. doi: 10.1016/0049-3848(89)90371-x. [DOI] [PubMed] [Google Scholar]
- Jørgensen M., Philips M., Thorsen S., Selmer J., Zeuthen J. Plasminogen activator inhibitor-1 is the primary inhibitor of tissue-type plasminogen activator in pregnancy plasma. Thromb Haemost. 1987 Oct 28;58(3):872–878. [PubMed] [Google Scholar]
- Kawano T., Morimoto K., Uemura Y. Urokinase inhibitor in human placenta. Nature. 1968 Jan 20;217(5125):253–254. doi: 10.1038/217253a0. [DOI] [PubMed] [Google Scholar]
- Kruithof E. K., Tran-Thang C., Gudinchet A., Hauert J., Nicoloso G., Genton C., Welti H., Bachmann F. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood. 1987 Feb;69(2):460–466. [PubMed] [Google Scholar]
- Lecander I., Astedt B. Specific plasminogen activator inhibitor of placental type PAI 2 occurring in amniotic fluid and cord blood. J Lab Clin Med. 1987 Nov;110(5):602–605. [PubMed] [Google Scholar]
- Librach C. L., Werb Z., Fitzgerald M. L., Chiu K., Corwin N. M., Esteves R. A., Grobelny D., Galardy R., Damsky C. H., Fisher S. J. 92-kD type IV collagenase mediates invasion of human cytotrophoblasts. J Cell Biol. 1991 Apr;113(2):437–449. doi: 10.1083/jcb.113.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liotta L. A., Goldfarb R. H., Brundage R., Siegal G. P., Terranova V., Garbisa S. Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res. 1981 Nov;41(11 Pt 1):4629–4636. [PubMed] [Google Scholar]
- Liu Y. X., Hu Z. Y., Liu K., Byrne S., Zou R. J., Ny T., d'Lacey C., Ockleford C. D. Localization and distribution of tissue type and urokinase type plasminogen activators and their inhibitors Type 1 and 2 in human and rhesus monkey fetal membranes. Placenta. 1998 Mar-Apr;19(2-3):171–180. doi: 10.1016/s0143-4004(98)90006-6. [DOI] [PubMed] [Google Scholar]
- Mackay A. R., Corbitt R. H., Hartzler J. L., Thorgeirsson U. P. Basement membrane type IV collagen degradation: evidence for the involvement of a proteolytic cascade independent of metalloproteinases. Cancer Res. 1990 Sep 15;50(18):5997–6001. [PubMed] [Google Scholar]
- Martin O., Arias F. Plasminogen activator production by trophoblast cells in vitro: effect of steroid hormones and protein synthesis inhibitors. Am J Obstet Gynecol. 1982 Feb 15;142(4):402–409. doi: 10.1016/s0002-9378(16)32380-8. [DOI] [PubMed] [Google Scholar]
- Meekins J. W., Pijnenborg R., Hanssens M., McFadyen I. R., van Asshe A. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynaecol. 1994 Aug;101(8):669–674. doi: 10.1111/j.1471-0528.1994.tb13182.x. [DOI] [PubMed] [Google Scholar]
- Nanaev A. K., Milovanov A. P., Domogatsky S. P. Immunohistochemical localization of extracellular matrix in perivillous fibrinoid of normal human term placenta. Histochemistry. 1993 Nov;100(5):341–346. doi: 10.1007/BF00268932. [DOI] [PubMed] [Google Scholar]
- Nilsson I. M., Felding P., Lecander I., Lennér C., Astedt B. Different types of plasminogen activator inhibitors in plasma and platelets in pregnant women. Br J Haematol. 1986 Feb;62(2):215–220. doi: 10.1111/j.1365-2141.1986.tb02924.x. [DOI] [PubMed] [Google Scholar]
- Ockleford C. D., Mongan L. C., Hubbard A. R. Techniques of advanced light microscopy and their applications to morphological analysis of human extra-embryonic membranes. Microsc Res Tech. 1997 Jul 1;38(1-2):153–164. doi: 10.1002/(SICI)1097-0029(19970701/15)38:1/2<153::AID-JEMT16>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
- Ockleford C., Malak T., Hubbard A., Bracken K., Burton S. A., Bright N., Blakey G., Goodliffe J., Garrod D., d'Lacey C. Confocal and conventional immunofluorescence and ultrastructural localisation of intracellular strength-giving components of human amniochorion. J Anat. 1993 Dec;183(Pt 3):483–505. [PMC free article] [PubMed] [Google Scholar]
- Pennica D., Holmes W. E., Kohr W. J., Harkins R. N., Vehar G. A., Ward C. A., Bennett W. F., Yelverton E., Seeburg P. H., Heyneker H. L. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature. 1983 Jan 20;301(5897):214–221. doi: 10.1038/301214a0. [DOI] [PubMed] [Google Scholar]
- Pijnenborg R., Anthony J., Davey D. A., Rees A., Tiltman A., Vercruysse L., van Assche A. Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynaecol. 1991 Jul;98(7):648–655. doi: 10.1111/j.1471-0528.1991.tb13450.x. [DOI] [PubMed] [Google Scholar]
- Pijnenborg R., Dixon G., Robertson W. B., Brosens I. Trophoblastic invasion of human decidua from 8 to 18 weeks of pregnancy. Placenta. 1980 Jan-Mar;1(1):3–19. doi: 10.1016/s0143-4004(80)80012-9. [DOI] [PubMed] [Google Scholar]
- Saksela O. Plasminogen activation and regulation of pericellular proteolysis. Biochim Biophys Acta. 1985 Nov 12;823(1):35–65. doi: 10.1016/0304-419x(85)90014-9. [DOI] [PubMed] [Google Scholar]
- Schaeren-Wiemers N., Gerfin-Moser A. A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes. Histochemistry. 1993 Dec;100(6):431–440. doi: 10.1007/BF00267823. [DOI] [PubMed] [Google Scholar]
- Vassalli J. D., Sappino A. P., Belin D. The plasminogen activator/plasmin system. J Clin Invest. 1991 Oct;88(4):1067–1072. doi: 10.1172/JCI115405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Verde P., Stoppelli M. P., Galeffi P., Di Nocera P., Blasi F. Identification and primary sequence of an unspliced human urokinase poly(A)+ RNA. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4727–4731. doi: 10.1073/pnas.81.15.4727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiman B., Csemiczky G., Marsk L., Robbe H. The fast inhibitor of tissue plasminogen activator in plasma during pregnancy. Thromb Haemost. 1984 Oct 31;52(2):124–126. [PubMed] [Google Scholar]
- Wun T. C., Reich E. An inhibitor of plasminogen activation from human placenta. Purification and characterization. J Biol Chem. 1987 Mar 15;262(8):3646–3653. [PubMed] [Google Scholar]
- Yagel S., Parhar R. S., Jeffrey J. J., Lala P. K. Normal nonmetastatic human trophoblast cells share in vitro invasive properties of malignant cells. J Cell Physiol. 1988 Sep;136(3):455–462. doi: 10.1002/jcp.1041360309. [DOI] [PubMed] [Google Scholar]
- Ye R. D., Wun T. C., Sadler J. E. cDNA cloning and expression in Escherichia coli of a plasminogen activator inhibitor from human placenta. J Biol Chem. 1987 Mar 15;262(8):3718–3725. [PubMed] [Google Scholar]
- de Boer K., Lecander I., ten Cate J. W., Borm J. J., Treffers P. E. Placental-type plasminogen activator inhibitor in preeclampsia. Am J Obstet Gynecol. 1988 Mar;158(3 Pt 1):518–522. doi: 10.1016/0002-9378(88)90016-6. [DOI] [PubMed] [Google Scholar]