Plasminogen activators and inhibitors may be important early in primate imp
lantation but evidence for this is sparse in non-human primates. We define
the expression of urokinase type plasminogen activator (uPA), tissue-type p
lasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1)
and type 2 (PAI-2), the receptor for uPA (uPAR) and fibrin/fibrinogen in mo
nkey implantation sites. In situ hybridization and immuno-histochemical loc
alization of rhesus monkey implantation sites (day 15-16 postovulation) ind
icate: (1) uPA mRNA is localized to placental trophoblast, epithelial plaqu
e and endometrial stroma. (2) tPA mRNA is mainly expressed in glandular cel
ls of endometrium. (3) PAI-1 expression is linked to a specific population
of trophoblasts that confront maternal cells, adding support to our view th
at it has a regulatory role in trophoblast invasion. (4) Localization of tP
A antigen confirms that uterine glands are the major source of tPA and that
it is also closely associated with fibrin(ogen) suggesting its possible fu
nction during implantation is fibrinolysis. (5) Unlike uPA mRNA, however, t
he distribution of uPA protein and its cell surface receptor uPAR suggests
that it mediates trophoblast invasion and plays a significant role in angio
genesis. (6) PAI-2, the inhibitor associated with pregnancy in humans, was
found in unidentified cells located specifically along the maternofetal jun
ction. This localization adjacent to areas of cell death at the maternofeta
l junction implies that it may have a role as a protective curtain with ant
i-apoptotic function. In conclusion our results suggest that gene expressio
n of PAs and PAIs in early implantation sites are tissue-specific, location
-sensitive and function-related. (C) 2001 Harcourt Publishers Ltd.