Effect of matrix metalloproteinase inhibitors on rat embryo development invitro

Matrix metalloproteinases appear to play a role in cell migration and tissu e remodeling and are postulated to be important in the development of embry os, We hypothesized that inhibition of these proteinases with the synthetic inhibitor batimastat or with endogenous tissue inhibitor of metalloprotein ases (TIMP) would alter in vitro development of day 9 rat embryos. Batimast at had a dose-related effect on embryo growth and viability following 48h i n culture, with significant inhibition at 1.0 mu M concentration, Dying cel ls were observed in many organs of living embryos. TIMP-2 at 3.0 mu g/ml ha d a similar effect on embryo growth. TIMP-1 alone or used in combination wi th TIMP-2 had no obvious effect, No focal malformations were observed. The effective concentrations are comparable to those which inhibit enzyme activ ity in cell culture. We conclude that matrix metalloproteinases are probabl y important in mammalian embryo development.