Maternal-Embryonic Cross-Talk

​In the 1990s, Professor David J. Barker identified a link between fetal/infant growth with cardiovascular diseases and modified adult disease models by including environmental programming during fetal/infant life. Intercellular communication is essential to allow multicellular and unicellular organisms to interact with their environment and for hosts to communicate with other cells. We investigated how the mother communicates with the preimplantation embryo before implantation and discovered that the maternal endometrium modifies the transcriptomics of the embryo under healthy and pathological conditions.

Our laboratory demonstrated that endometrial cells secrete particular molecules and extracellular vesicles into the endometrial fluid and that the embryo can capture these secreted factors before implantation to initiate pregnancy. We focus on further understanding this crucial dialogue between the embryo and the mother as the basis of creating a new preconception care concept.

Endometrial tissue undergoes complete remodeling throughout each menstrual cycle, which involves reconstructing several differentiated tissue types: vascular tissue, stromal tissue, and the luminal and glandular epithelium. In the human endometrium, the stem cell niche has been identified in the basal layer, specifically in the endothelium of the spiral arterioles. Our group demonstrated the presence of immature cells; however, the coexistence of immature populations, the common origin of several lineages, cannot be ruled out.

Our research group analyzes gene expression in different menstrual cycle phases to identify progenitor cells responsible for endometrial regeneration throughout the distinct cell layers. We have identified candidate populations that could harbor cells that can regenerate the endometrial epithelium and stroma; we are currently validating their stem cell capacity using advanced three-dimensional cell culture models.

Endometrial receptivity is a postovulatory process of endometrial remodeling to prepare for pregnancy, including all the morphological and molecular modifications known as plasma membrane transformation. Menstruation is a resetting process that occurs across the reproductive lifespan – from menarche to menopause – to prepare the uterine cavity for synchrony of the blastocyst’s arrival during the endometrial receptivity window of implantation (WOI). This allows the blastocyst to adhere and triggers the completion of decidualization of stromal compartments that control trophoblast invasion and subsequent placentation.

Prior research in our laboratory enabled the discovery of a transcriptomic signature of human endometrial receptivity. This finding has been clinically validated in more than 20 scientific peer-reviewed articles in cases of repeated implantation failure. We now focus on deep endometrial characterization using single-cell analysis to provide unprecedented insights into the transcriptomic, genomic, and spatial alterations in this critical female organ throughout the menstrual cycle and across the patient’s lifespan.