Perinatology.  2018 Dec;29(4):170-174. 10.14734/PN.2018.29.4.170.

The Effect of Progesterone on Tumor Necrosis Factor-α Induced Matrix Metalloproteinase-9 in Human Choriodecidual Membranes

• Choi SJ
• Sohn JH
• Han KH
• Park EY
• Kang J
• Chung IB

• KMID: 2430220
• DOI: http://doi.org/10.14734/PN.2018.29.4.170

Abstract

OBJECTIVE
Progesterone is used to prevent recurrent preterm delivery, however the molecular mechanisms of its effect are incompletely understood. The objective of this study was to determine the effect of progesterone on tumor necrosis factor (TNF)-α-induced matrix metalloproteinase (MMP)-9 activity in human choriodecidual (CD) membranes.
METHODS
We collected CD membranes from women with uncomplicated term pregnancies who were scheduled for elective cesarean delivery (n=10). CD membranes (1×1 cm) were incubated in tissue culture media at 37℃. We pre-treated the CD membranes with progesterone (P4), 17α-hydroxyprogesterone caproate (17P), promegestone (R5020), or vehicle (ethanol) for 24 hours. The CD membranes were subsequently treated with TNF-α (with continued progesterone treatment) for 48 hours, then media was harvested for measuring MMP-9 activity by zymography and total protein was isolated from CD membrane tissues for MMP-9 expression by western blot analysis.
RESULTS
P4, 17P, and R5020 significantly reduced TNF-α-induced MMP-9 activity in fetal membrane tissue samples (P=0.0078, P=0.0156, and P=0.0391, respectively) by zymography. Western blot analysis also showed decreased expression of MMP-9 in progesterone pretreated groups (P=0.0313).
CONCLUSION
Progesterone reduces TNF-α-induced MMP-9 activity in human CD membranes. These findings may provide further support for the role of progesterone in preventing preterm birth.

Keyword

Chorion; Matrix metalloproteinase 9; Preterm labor; Progesterone; Tumor necrosis factor-alpha

MeSH Terms

Blotting, Western
Chorion
Culture Media
Extraembryonic Membranes
Female
Humans*
Matrix Metalloproteinase 9*
Membranes*
Necrosis*
Obstetric Labor, Premature
Pregnancy
Premature Birth
Progesterone*
Promegestone
Tumor Necrosis Factor-alpha
Culture Media
Matrix Metalloproteinase 9
Progesterone
Promegestone
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Effects of progesterone and TNF-α on MMP-9 protein expression in choriodecidual membranes. Choriodecidual membranes were isolated, cultured, and pretreated with P4, 17P, R5020, or an EtOH vehicle for 24 hours, and treated with TNF-α for 48 hours. Densitometric analysis of western blotting of MMP-9/β-actin (top). Representative Western blot (bottom). Shown are mean±standard deviation (n=6). MMP, matrix metalloproteinase; OMEM, Opti-Minimum Essential Media; EtOH, ethanol; TNF, tumor necrosis factor; P4, progesterone; 17P, 17α-hydroxyprogesterone caproate; R5020, promegestone.

• 

  Fig. 2 Effects of progesterone and TNF-α on MMP-9 activity in choriodecidual membranes. Choriodecidual membranes were isolated, cultured, and pretreated with P4, 17P, R5020, or an EtOH as a vehicle for 24 hours, and treated with TNF-α for 48 hours. Densitometric analysis of zymography of MMP-9 (top). Representative zymography (bottom). Shown are mean±standard deviation (n=8). MMP, matrix metallopro-teinase; OMEM, Opti-Minimum Essential Media; EtOH, ethanol; TNF, tumor necrosis factor; P4, progesterone; 17P, 17α-hydroxyprogesterone caproate; R5020, promegestone.

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