Polarized release of matrix metalloproteinase-2 and-9 from cultured human placental syncytiotrophoblasts

The large increase in placental surface area and fetal villous vascular dev elopment in the third trimester of pregnancy requires degradation and refor mation of the placental basal lamina. Degradation is carried out by matrix metalloproteinases (MMPs) secreted by adjacent cells. Although the gelatina ses, MMP-2 and MMP-9, which are released by extravillous cytotrophoblasts ( CTs) are believed to play crucial roles in early placental expansion, neith er has been reported in third trimester villous trophoblasts nor has approp riate (basolateral) release of any MMP by the highly polarized syncytiotrop hoblast (ST) been demonstrated. We demonstrated villous trophoblast express ion of both MMP-2 and MMP-9 by in situ immunohistochemistry and by Western blot analysis and zymography of lysates and culture supernatants of highly purified villous CTs. We also found that epidermal growth factor (EGF)-stim ulated CT differentiation into ST and stimulation by the phorbol diester, P MA, both increase MMP-9 secretion. The direction of MMP release was determi ned with confluent cultures of ST on porous membranes. We found that >90% o f MMP-2 and MMP-9 were released from the basolateral surface. We conclude t hat villous STs express and release gelatinases from their basolateral surf aces in a regulated manner and suggest that such polarized release may be i mportant to villous tissue remodeling.