Inhibition of proteolytic degradation of the basement membrane during embryogenesis impacts collagen IV biosynthesis and cell differentiation

Abstract

Preimplantation embryo development involves a series of complex biological processes. Previous studies have described how L-pro is naturally found in hydrolysed collagen, specifically collagen type IV within the embryo’s basement membrane, and has shown to play an important role in biological function. During collagen biosynthesis, MMPs will break down the basement membrane, releasing L-pro facilitating the cell differentiation. The secretion of L-pro into the microenvironment is driven by intracellular prolidase (PEPD) which plays a crucial role in the recycling of L-proline for collagen synthesis.

Our study aimed at observing how by inhibiting proteolytic degradation of the BM during preimplantation development will potentially limit the natural release of L-pro from COL4, impacting biological functions associated with embryo development.

As COL4 is made up of approximately 25% of the amino acid residues and since collagen is one of the most abundant proteins in the human body, the degradation of collagen IV during collagen synthesis would potentially provide an excellent source since L-proline. The collagen is initially broken down by specific MMPs, and the degradation continues as a result of protease activity. Lastly, the final. Specific and non-specific MMP inhibitors will target enzymes responsible for the breakdown of the embryo’s ECM, limiting or potentially preventing a sufficient concentration of L-proline.

By introducing a specific inhibitor that actively targets the enzymes responsible for the breakdown of the ECM, it can be hypothesized that this action will restrict the release of L-proline subsequently impacting cell differentiation. As two specific gelatinases have been identified in having a significant role in basement membrane (BM) degradation, they, along with their associated pathways will be the primary focus in our experiments and how obstructing their activity will impact the biological functions associated with healthy embryo development.