| Exploring the metabolic pathways involved in the pre-implantation embryo development and their use as targets for improving embryo implantation rates

Arieh Moussaieff Ph.D. Reut Bruck, Natalya Kogan, Assaf Ben-Meir (Hadassah Medical Center)

Understanding the complex process of embryo implantation is a major goal of developmental biology. Such knowledge may also have important medical, social and economic implications, as 20-30% of all couples are temporarily (with 10% of them permanently) involuntarily childless. Of lost pregnancies, 75% are due to failure of implantation. Over the past several decades, it has become clear that shifts in different metabolic pathways determine the outcome of implantation, pointing to its regulation by a metabolic network.

 

Optimization of the metabolic environment to be favorable for embryo implantation is currently at the core of assisted conception programmes. However, despite intensive research, the pathways that are involved in implantation, and how they interact, are still poorly understood. Although no systemic overview for metabolic processes during implantation has been offered thus far, specific metabolic pathways have been suggested to be involved in embryo implantation including ovarian hormones signaling pathways, central carbon metabolism pathways, inflammatory signaling as well as lysophosphatidic acid signaling.

Importantly, a large volume of literature established an important role for the endocannabinoid system in the implantation of the mammalian embryo.

Advances in analytical chemistry and in bio-informatic software provide a means for the unbiased analysis of the metabolic processes by metabolomics: the profiling of the metabolome. The metabolome represents the collection of all metabolites in a biological sample. A systematic study of the unique chemical fingerprints that are the result of specific cellular processes will shed important new light on the process of embryo implantation.

­­­We are looking into the metabolism and specifically into endocannabinoid metabolism of the pre-implanted embryo using medium from In Vitro Fertilization of human embryos. We are also utilizing stem cell technologies to study the metabolic maturation of the implanted embryo, and developed a multi-cellular model for the examination of cellular metabolic interactions during implantation.  

Key words: Metabolomics; embryo implantation; embryonic stem cells; trophectoderm; endometrium