High levels of human chorionic gonadotropin retard first trimester trophoblast invasion in vitro by decreasing urokinase plasminogen activator and collagenase activities.
Trophoblast cells of the blastocyst and of the first trimester placenta penetrate the endometrial basement membrane during the process of implantation and placental development. However, this invasive capacity seems to be restricted to the fetomaternal interface, as few trophoblast cells can be identified in the decidua, and trophoblasts rarely penetrate the maternal blood vessels. We have shown that the high invasive ability of first trimester human trophoblasts in vitro depends on collagenase activated by plasmin generation. In our study we used invasive first trimester trophoblast cells in conjunction with as in vitro amnion invasion assay to assess the role of hCG in the invasive process. hCG inhibited trophoblast invasion capacity in a dose-dependent fashion but exerted no effect on the ability of the trophoblasts to attach to the basement membrane. The activity of collagenase by trophoblasts (determined by zymography) was down-regulated by hCG, again in a dose-dependent manner. In contrast, hCG had no effect on production of the tissue inhibitor of metalloproteinases. Similar inhibitory effects of hCG on urokinase-plasminogen activator (uPA) and the activity of trophoblast-conditioned media were shown (measured by degradation of S-2444). The hCG effect on collagenase production was not mediated by the expression of procollagenase messenger RNA (mRNA), the expression of the mRNA encoding tissue inhibitor of metalloproteinase, or the expression of uPA mRNA, suggesting posttranscriptional control of hCG action. High levels of hCG attenuated the activity of commercial uPA but had no effect on commercial collagenase activity. These observations suggest that hCG may play a role in the trophoblast invasion process by inhibition of uPA activity, in turn decreasing collagenase activity and thereby reducing trophoblast cell invasion.
Yagel
S
S
Department of Obstetrics and Gynecology, Hadassah Mount Scopus, Jerusalem, Israel.
Geva
T E
TE
Solomon
H
H
Shimonovitz
S
S
Reich
R
R
Finci-Yeheskel
Z
Z
Mayer
M
M
Milwidsky
A
A
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D017364:Collagenases / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000235:genetics
D006063:Chorionic Gonadotropin; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D008666:Metalloendopeptidases