The role of metalloproteinase and hypoxia conditions in endometrial cells and embryo implantation

In the process of implantation, metalloproteinase enzymes play a key role in basement membrane degradation and endometrial extracellular matrix. The activity of these enzymes is impeded by binding Tissue Inhibitors of Metalloproteinase (TIMP). The oxygen concentration in the mammalian uterus at the time of implantation is about ۲-۵%. It is seen that the imposition of hypoxia on cancer cells increases the expression of metalloproteinase enzymes and reduces the expression of metalloproteinase inhibitors, resulting in increased cell invasion. To know the effect of Hypoxia-Inducible Factor (HIF) and other related factors, we decided to evaluate hypoxic conditions on endometrial epithelial cells of the uterus and the role of matrix metalloproteinases (MMPs) on angiogenesis and invasion of the embryo during implantation. In this study, human and mouse endometrial epithelial cells were incubated for ۲۴-۴۸ hours in hypoxic conditions. Subsequently, the expression level of TIMP-۱ was measured in mouse and human epithelial cells by Real-Time PCR technique. The cell viability in hypoxic conditions was evaluated by MTT assay. Our results demonstrated that hypoxia reduced the quantitative gene expression of TIMP-۱ in the human and mouse endometrial epithelial cells compared to the control group. It can be concluded that applying hypoxic conditions by reducing the TIMP-۱ expression and consequently increasing MMP expression, may improve the embryo implantation rate.

Keywords:

Implantation , Embryo , Hypoxia , TIMP-۱ , MMPs