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

Natalia S. Carvalho, Antonio F. Moron, Steven S. Witkin, Ramkumar Menon, Sergio Cavalheiro, Mauricio M. Barbosa, Herbene J. Milani, Stephanno G. Sarmento, Marcia M. Ishigai

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
JournalJournal of Maternal-Fetal and Neonatal Medicine
StateAccepted/In press - Jan 1 2020



  • Collagen
  • fetal membrane healing
  • fetal membrane repair
  • matrix metalloproteinases
  • myelomeningocele
  • open fetal surgery

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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