Rat amnion type IV collagen composition and metabolism: implications for membrane breakdown.

We report here that rat amnion type IV collagens are composed primarily of alpha1(IV) and alpha2(IV) chains. Amnion basement membrane collagens were more sensitive to degradation by collagenases than were adult rat kidney basement membrane collagens, which are enriched in alpha3(IV), alpha4(IV), and alpha6(IV) chains. Amnion type IV collagen content per unit of protein was markedly reduced by Day 21 of pregnancy, the day of delivery. Increased amnion levels of matrix metalloproteinase (MMP)-2 and MMP-9, gelatinases that degrade type IV collagen, were found by Day 21, suggesting that collagen breakdown was responsible, in part, for the decline in amnion type IV collagen. Infection of organ cultures of Day 18 rat amnions with a recombinant adenovirus expressing MMP-9 (AdMMP-9) caused release of collagen fragments detected as hydroxyproline in the culture fluid, amnion cell detachment, and apoptosis. The AdMMP-9-induced apoptosis was prevented by the MMP inhibitor batimastat. These findings suggest that MMPs are implicated in anoikis and apoptotic death of amnion cells, and may be part of a complex program of fetal membrane remodeling that occurs before delivery.