Histological response and expression of collagen, metalloproteinases MMP-1 and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 in fetal membranes following open intrauterine surgery: an experimental study.

Objective: To characterize aspects of the repair process by evaluating the tissue collagen density, metalloproteinases and tissue inhibitor of matrix metalloproteinases in the fetal membranes following open fetal surgery for myelomeningocele (MMC).Design: Experimental.Setting: Two Brazilian hospitals in 2013-2014.Population: 30 fetal membranes collected after elective cesarean deliveries, in patients who underwent open fetal surgery for MMC intrauterine repair.Methods: Regions within and surrounding the scar area and regions distant from the surgical site were evaluated for collagen concentration and expression of MMP-1, MMP-9, TIMP-1 and TIMP-2.Results: Collagen was increased in regions of scar formation (14.4 +/- 2.7%) as compared to unaffected regions (8.0 +/- 1.9%) (p < .001). The mean score of MMP-9 in the area of both the scar and suture was also increased above that observed in normal regions (p < .05). Conversely, MMP-1 was reduced in the scar when compared to the normal region and the area adjacent to the scar (suture region) (p < .05). TIMP-1 was increased in the suture region compared to the normal region (p < .05) while TIMP-2 was reduced in the scar region when compared to the other two regions (p < .05). The membrane repair process was also influenced by the number of previous pregnancies and gestational age at the time of surgery.Conclusion: Reparative activity of the fetal membrane after open fetal surgery involves up-regulation of collagen production and differential involvement of MMPs and TIMPs.