Embryonic Mediators of Embryo-Uterus Communication, Implantation and Pregnancy

Successful reproduction in eutherian mammals requires intimate connections between the embryo and uterus, involving adhesion, attachment and placentation, with or without invasion of the endometrium. The complex dialogue between embryo and uterus involves numerous molecules and pathways. The study of the mechanisms driving early embryo-uterus interactions has historically been challenging, particularly discovering the embryo-expressed molecules. Some components of the interactions have been known for decades, but many have been revealed in recent years through innovative transcriptome studies, studies of the contents and functions of extracellular particles, use of in vitro three-dimensional organoids, genetic studies, approaches for dissecting the regulation of maternal immune system cells, and many other approaches. This review focuses on embryo-expressed molecules that support implantation and embryo attachment, implantation and pregnancy establishment. Both classical and recent discoveries are examined, encompassing results from human, murine, livestock and comparative studies. Opportunities for further mechanistic insights are considered. Additionally, the review considers the potential for agricultural and clinical applications of the more recently identified molecular players and mechanisms for enhancing reproductive success or for providing new approaches to contraception.