INVOLVEMENT OF TROPHOBLAST IN EMBRYO IMPLANTATION - REGULATION BY PARACRINE FACTORS

In order to investigate the regulatory role of only one endometrial ce ll type on trophoblastic invasion, we explored the effects of culture medium conditioned by in vitro decidualised stromal cells (DCM) and of insulin-like growth factor binding protein-1 (TGFBP-1, the main secre tory product of decidual cells) on the trophoblastic secretion of gela tinases and tissue inhibitor of metalloproteinases (TIMP-1). First tri mester cytotrophoblastic cells (CTB) were obtained from abortions and cultured in vitro in presence or absence of DCM or IGFBP-1. Secreted g elatinases were analysed in the culture supernatants by zymography and by measurements of the total gelatinolytic activity. Tissue inhibitor of metalloproteinases (TIMP-1) was measured by a commercially availab le immunoassay. DCM inhibited the total gelatinolytic activity of CTB but increased trophoblastic MMP-9 and TIMP-1. In contrast, IGFBP-1 inc reased the total gelatinolytic activity and TIMP-1 and had no effect o n MMP-2 and MMP-9. We conclude that a factor secreted by decidual cell s (possibly TGF beta) inhibits the total gelatinolytic activity of tro phoblast by increasing TIMP-1 but other factors, as yet unidentified, increase MMP-2 and MMP-9 to an extent which does not shift the equilib rium between the gelatinases and TIMP-1 in favour of the gelatinases. In contrast to DCM, IGFBP-1 increases the total gelatinolytic activity probably by stimulating another gelatinase (stromelysin-l?) as MMP-2 and MMP 9 are unchanged by IGFBP-1. The possibility of an integrin med iated effect of IGFBP-1 on CTB is discussed. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.