Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines.
Several clinical situations require continuous glucocorticoid (GC) treatment during pregnancy. A well-known deleterious side effect of such treatment is the higher incidence of growth-restricted fetuses, for which a too shallow trophoblast invasion is presently hypothesised as the underlying cause. This study investigated whether the synthetic GC triamcinolone acetonide (TA) influences proliferation, invasion and endocrine activity of human trophoblast. BeWo and JEG-3 choriocarcinoma cell lines both express GC receptors (western blotting) and were used as models for human trophoblast. JAR devoid cells of GC receptor were used as negative control. The cells were cultured for 48 h without (control) or with 0.5, 5 and 50 microM TA. In the presence and absence of serum, proliferation was determined by cell counting and measuring the cell cycle regulating protein cyclin B1 (Western blotting); invasion was determined by a conventional Matrigel invasion assay and by measuring the secretion (ELISA) of matrix-metalloproteinases (MMP-2, MMP-9) into the culture medium; endocrine activity was assessed by measuring the levels of human chorionic gonadotropin (ELISA) into the culture medium. TA altered the number of viable and dead cells as well as cyclin B1 levels and, to a lesser extent, invasion of BeWo and JEG-3, with a strong influence of serum. BeWo and JEG-3 cells reacted differently and in most instances reverse. In the cell lines used as models of human trophoblast, TA alter some functions relevant to proliferation and invasion, and suggest that caution should be exercised when treating women with GCs during pregnancy.
Mandl
M
M
Clinic of Obstetrics and Gynaecology, Medical-University of Graz, Auenbruggerplatz 14, A-8036, Graz, Austria.
Ghaffari-Tabrizi
N
N
Haas
J
J
Nöhammer
G
G
Desoye
G
G
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003094:Collagen; D019926:Cyclin B / Q000032:analysis / Q000378:metabolism; D056744:Cyclin B1; D004338:Drug Combinations; D010064:Embryo Implantation / Q000187:drug effects*; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007797:Laminin; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011509:Proteoglycans; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000494:pharmacology*; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
C534699:CCNB1 protein, human; D006063:Chorionic Gonadotropin; D019926:Cyclin B; D056744:Cyclin B1; D004338:Drug Combinations; D004792:Enzyme Precursors; D005938:Glucocorticoids; D007797:Laminin; D011509:Proteoglycans; D011965:Receptors, Glucocorticoid; C059485:matrigel; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; C120487:pro-matrix metalloproteinase 9; C069860:progelatinase; D020780:Matrix Metalloproteinase 9; D014222:Triamcinolone Acetonide