How Mechanical Forces Change the Human Endometrium during the Menstrual Cycle in Preparation for Embryo Implantation

The human endometrium is characterized by exceptional plasticity, as evidenced by rapid growth and differentiation during the menstrual cycle and fast tissue remodeling during early pregnancy. Past work has rarely addressed the role of cellular mechanics in these processes. It is becoming increasingly clear that sensing and responding to mechanical forces are as significant for cell behavior as biochemical signaling. Here, we provide an overview of experimental evidence and concepts that illustrate how mechanical forces influence endometrial cell behavior during the hormone-driven menstrual cycle and prepare the endometrium for embryo implantation. Given the fundamental species differences during implantation, we restrict the review to the human situation. Novel technologies and devices such as 3D multifrequency magnetic resonance elastography, atomic force microscopy, organ-on-a-chip microfluidic systems, stem-cell-derived organoid formation, and complex 3D co-culture systems have propelled the understanding how endometrial receptivity and blastocyst implantation are regulated in the human uterus. Accumulating evidence has shown that junctional adhesion, cytoskeletal rearrangement, and extracellular matrix stiffness affect the local force balance that regulates endometrial differentiation and blastocyst invasion. A focus of this review is on the hormonal regulation of endometrial epithelial cell mechanics. We discuss potential implications for embryo implantation.