Matrix Metalloproteinases-2 and -9 and Their Endogenous Tissue Inhibitors in Tissue Remodeling After Sealing of the Fetal Membranes in a Sheep Model of Fetoscopic Surgery
Restricted accessResearch articleFirst published online May, 2002
Matrix Metalloproteinases-2 and -9 and Their Endogenous Tissue Inhibitors in Tissue Remodeling After Sealing of the Fetal Membranes in a Sheep Model of Fetoscopic Surgery
Objectives:We studied collagen plugging of the fetoscopic access site in an in vivo fetal lamb model for fetoscopic surgery and possible role for matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitors (TIMPs).
Methods:Eight ewes had fetoscopic balloon occlusion of the trachea as an experimental treatment for congenital diaphragmatic hernia between days 88 and 99 of gestation (term 145 days) with sampling of amniotic, allantoic, and tracheal fluid. Nonoperated cotwins were used as controls. The fetoscopy port was closed using a collagen plug. Ten days (range 9-12) later, fluids were sampled and plug sites collected for histologic analysis. Activity of MMP-2 (72 kDa, gelatinase A) and MMP-9 (92 kDa, gelatinase B) was determined in the fluids by zymography and secretion of TIMPs (27-30 kDa; TIMP-1, glycosylated TIMP-3 and TIMP-4, 24 kDa; unglycosylated TIMP-3, 21 kDa; TIMP-2) by reverse zymography and quantified by densitometric analysis.
Results:No pregnancy was complicated by amniorhexis or preterm labor. At cesarean, normal volumes of amniotic and allantoic fluid were present in all cases. Histology of the plug sites revealed good integration of the collagen plug without complete restoration of membrane integrity. MMP-2, MMP-9, and TIMps were detected in all fluids. In the operated animals, significantly (P < .05) higher activity of MMP-9 was found in amniotic fluid, with lower concentrations of TIMPs in allantoic fluid (P < .01). Tracheal occlusion was associated with a significant (P < .02) increase in both MMP-2 and -9 in tracheal fluid.
Conclusion:Collagen plugging of the fetoscopic access port sites in sheep resulted in functionally effective sealing of the fetal membranes. Changes in MMP-2, MMP-9, and TIMPs suggest an active remodeling of both the fetal lung and the fetal membranes.
3. Singer AJ, Clark RAF. Cutaneous wound healing. N Engl J Med1999;341:738-746.
4.
4. Devlieger R, Deprest JA, Gratacos E, et al. Matrix metalloproteinases -2 and -9 and their endogenous tissue inhibitors in fetal membrane repair following fetoscopy in a rabbit model. Mol Hum Reprod2006;6:479-485.
5.
5. Devlieger R, Gratacos E, Wu J, et al. An organ-culture for in vitro evaluation of fetal membrane healing capacity. Eur J Obstet Gynaecol Reprod Biol2000;92:145-150.
6.
6. Gratacos E, Wu J, Yesildaglar N, et al. Successful sealing of fetoscopic access sites with collagen plugs in the rabbit model. Am J Obstet Gynecol2000;182:142-146.
7.
7. Ramsey EM. The placenta: Human and animal. New York: Praeger Publishers1982;141-145.
8.
8. Luks FI, Deprest JA, Vandenberghe K, et al. Fetroscopy-guided fetal endoscopy in a sheep model. J Am Coll Surg1994;178:609-612.
10. Riley SC, Webb CJ, Leask R, et al. Involvement of matrix metalloproteinases 2 and 9, tissue inhibitor of metalloproteinases and apoptosis in tissue remodelling in the sheep placenta. J Reprod Fertil2000;118:19-27.
11.
11. Luks FI, Deprest JA, Peers KH, et al. Gelatin sponge plug to seal fetoscopy port sites: Technique in ovine and primate models. Am J Obstet Gynecol1999;181:995-996.
12.
12. Flageole H, Evrard VA, Vandenberghe K, et al. Tracheoscopic endotracheal occlusion in the ovine model: Technique and pulmonary effects. J Pediatr Surg1997;32:1328-1331.
13.
13. Riley SC, Leask R, Chard T, et al. Secretion of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases into the intrauterine compartments during early pregnancy. Mol Hum Reprod1999;5:376-381.
14.
14. Riley SC, Leask R, Denison FC, et al. Secretion of tissue inhibitors of matrix metalloproteinases by human fetal membranes, decidua and placenta at parturition. J Endocrinol1999;162:351-359.
15.
15. Sopher D. The response of rat fetal membranes to injury. Ann R Coll Surg Engl1972;51:240-249.
16.
16. Bryant-Greenwood GD. The extracellular matrix of the human fetal membranes: Structure and function. Placenta1998;19:1-11.
17.
17. Pilcher BK, Wang M, Qin XJ, et al. Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity. Ann N Y Acad Sci1999;878:12-24.
18.
18. Fortunato SJ, Menon R, Lombardi SJ. MMP/TIMP imbalance in amniotic fluid during PROM: An indirect support for endogenous pathway to membrane rupture. J Perinat Med1999;27:362-368.
19.
19. Athayde N, Romero R, Gomez R, et al. Matrix metalloproteinases-9 in preterm and term human parturition. J Matern Fetal Med1999;8:213-219.
20.
20. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: Evolution, structure and function. Biochim Biophys Acta2000;1477:267-283.
21.
21. Deprest JA, Evrard VA, Verbeken EK, et al. Tracheal side effects of endoscopic balloon tracheal occlusion in the fetal lamb model. Eur J Obstet Gynecol Reprod Biol2000;92:119-126.
22.
22. Nardo L, Hooper SB, Harding R. Lung hypoplasia can be reversed by short-term obstruction of the trachea in fetal sheep. Pediatr Res1995;38:690-696.
23.
23. Evrard VA, Verbeken EA, Vandenberghe K, et al. Endoscopic in utero tracheal plugging in the fetal lamb to treat congenital diaphragmatic hernia. J Am Assoc Gynecol Laparosc1996;3:S11-S11.
