Vaginal indomethacin increases TIMP-2 levels in amniotic fluid and fetal membranes in a rabbit model for RU486-induced preterm birth

Abstract

FETAL MEMBRANES IN A RABBIT MODEL FOR RU486-INDUCED PRETERM BIRTH WILBERT FORTSON (F), KAY BEHARRY, STEPHEN NAGEOTTE, AMANDA JAN, TAMEROU ASRAT, HOUCHANG MODANLOU, University of California, Irvine, Maternal Fetal Medicine, Irvine, California, University of California, Irvine, Pediatrics, Orange, California, Miller Children’s Hospital, Women’s Pavilion, Maternal Fetal Medicine, Long Beach, California, Miller Children’s Hospital, Women’s Pavilion, Irvine, California OBJECTIVE: Preterm parturition and rupture of fetal membranes are associated with decreased amniotic fluid tissue inhibitor of metalloproteinases (TIMP-2), an endogenous inhibitor of MMPs. We examined the hypothesis that vaginal indomethacin will increase TIMP-2 levels in a rabbit model for RU468-induced preterm birth in amniotic fluid (AF) and fetal membranes (FM) in a rabbit model for RU468-induced preterm birth. STUDY DESIGN: Pregnant rabbits were induced with a single 50 mg IM dose of RU486 at day 24 of a 32 day gestation. The animals received either oral indomethacin (20 mg in a vehicle suspension, OI), a methylcellulose vehicle suspension (OV), a vaginal suppository of indomethacin (20 mg in cocoa butter, VI), or a vaginal suppository of cocoa butter only (placebo, VP) once daily for 2 days. At delivery (expulsion of at least 1 fetus), AF and FM were collected for MMP-2, and -9 activity; and TIMP-1 and -2 levels. RESULTS: Data are meanGSEM. There were not differences in MMP-9 activity. CONCLUSION: Elevated TIMP-2 levels in the amniotic fluid and fetal membranes with vaginal indomethacin suggest decreased breakdown of extracellular matrix and inhibition of membrane rupture in our model.