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Published on: June 26, 2018
Expression and implications of tissue inhibitor of metalloproteinases-4 in mouse embryo
Jian Zhang1, Yun-Ge Zhao, Yu-Jing Cao
1State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, People's Republic of China.
Abstract:
Matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), and MMP-TIMP interactions may contribute to the highly programmed process of embryo implantation. The loss of the delicate MMP-TIMP balance may lead to abnormal implantation. The role of TIMP-4 in mouse implantation has not been reported. This study examined mRNA and protein expression levels of TIMP-4 in the blastocyst and uteri of pregnant mice. We also investigated the effects of a specific TIMP-4 antibody on embryo outgrowth and on the gene and protein expression levels of two gelatinases. High levels of TIMP-4 mRNA and protein were detected in day 3-5 embryos and in the trophoblast cells of mice blastocysts, suggesting that TIMP-4 may be involved in embryo implantation. Furthermore, TIMP-4 antibody promoted blastocyst outgrowth in a dose-dependent manner, but had no effect on blastocyst adhesion to extracellular matrix. A specific TIMP-4 antibody also increased mRNA and protein expression levels and the enzymatic activities of gelatinase A (MMP-2) and gelatinase B (MMP-9). This study suggests that TIMP-4 may restrict mouse blastocyst outgrowth and embryo implantation by inhibiting the activities of MMP-2 and -9.
Insights
Tissue inhibitor of metalloproteinases-4 (TIMP-4) plays a role in mouse embryo implantation. TIMP-4 may restrict blastocyst outgrowth by inhibiting matrix metalloproteinases (MMP-2 and MMP-9).
Area of Science:
- Reproductive biology
- Developmental biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) are crucial for embryo implantation.
- Imbalance in MMP-TIMP interactions can lead to implantation failure.
- The specific role of TIMP-4 in mouse implantation is not well understood.
Purpose of the Study:
- To investigate the expression of TIMP-4 in mouse blastocysts and uteri during early pregnancy.
- To determine the effect of TIMP-4 on blastocyst outgrowth and adhesion.
- To examine the influence of TIMP-4 on gelatinase (MMP-2 and MMP-9) activity.
Main Methods:
- Quantitative analysis of TIMP-4 mRNA and protein expression in mouse embryos and uterine tissues.
- In vitro culture of mouse blastocysts with a specific TIMP-4 antibody.
- Assessment of blastocyst outgrowth, adhesion to extracellular matrix, and gelatinase activity.
Main Results:
- High levels of TIMP-4 mRNA and protein were observed in mouse blastocysts (days 3-5) and trophoblast cells.
- TIMP-4 antibody significantly promoted blastocyst outgrowth in a dose-dependent manner.
- TIMP-4 antibody increased the expression and enzymatic activity of MMP-2 and MMP-9.
Conclusions:
- TIMP-4 is expressed in mouse blastocysts and may be involved in regulating embryo implantation.
- TIMP-4 appears to restrict mouse blastocyst outgrowth.
- TIMP-4 may inhibit blastocyst implantation by suppressing the activity of MMP-2 and MMP-9.
