Dysregulated expression of matrix metalloproteinases and their inhibitors may participate in the pathogenesis of pre-eclampsia and fetal growth restriction

Abstract

Background: Trophoblast invasion into the maternal endometrium serves an important function in human pregnancy. Dysregulation of the finely controlled process of trophoblast invasion can result in a wide spectrum of pregnancy abnormalities.

Aims: We aimed to elucidate the relationship between the expression of matrix metalloproteinases and pregnancy complication.

Study design: The study group consisted of placental bed biopsy tissues obtained from normal vaginal deliveries (N=15), normal cesarean deliveries (N=15), pre-eclampsia (N=24) and fetal growth restriction (FGR) (N=10). We evaluated the expressions of MMP-2, -8, -9, -11, -19, -15 (MT2-MMP), -16 (MT3-MMP), and -24 (MT5-MMP), as well as TIMP-1 and -3, by applying Western blot and immunohistochemistry methods.

Subjects: Human placental tissues were used for this study.

Outcome measures: The expressions of MMP-2, -8, -9, -11, -19, -15 (MT2-MMP), -16 (MT3-MMP), and -24 (MT5-MMP), as well as TIMP-1 and -3 in human placenta tissues.

Results: Compared with those in normal pregnancies, the expression of MMP-2, -8, -9 and -11 was downregulated in villous tissues of pre-eclampsia and FGR cases (p<0.05). TIMP-1 and -3 were increased in pre-eclampsia and FGR (p<0.05). No significant difference was found between normal vaginal deliveries and cesarean deliveries.

Conclusions: We speculate that the change in invasion-associated proteinase expression will affect placental development and may thus contribute to the development of complicated pregnancies.

Keywords: Fetal growth restriction; Matrix metalloproteinase; Placenta; Pre-eclampsia; Tissue inhibitor of metalloproteinase; Trophoblast invasion; Trophoblast-related diseases.