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

Abstract

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.

Keywords:

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

Acknowledgments

We would like to thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES, Brazil, for a PhD scholarship received by NSC and the Centro de Estatistica Aplicada – CEA- IME/USP, Brazil, for statistical analysis.

Ethical approval

The study protocol was approved by the Institutional Research Ethics Board (# 887.954, 11/18/2014).

Author contributions

AFM and MMI designed the study; NSC wrote the first draft of the manuscript; AFM, SC, MMB, HJM, SGS participated in fetal surgery and collected the fetal membranes; MMI and NSC performed the histological evaluation; SSW and RM made significant revisions to the first draft; all authors revised successive versions of the article and approved the final article.

Disclosure statement

The authors have no conflicts of interest or disclosures to declare. Completed disclosure of interest forms are available to view online as supporting information.