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

Abstract

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.

Extracellular matrix and extracellular matrix-derived materials in reproductive medicine

“…[36] To better receive the embryo, the endometrial epithelial cells lose polarity, and the intercellular space becomes wider and is inserted by the ECM. [37] The ECM composition has undergone overall changes, especially collagen type IV, laminin, and fibronectin. [37,38] According to staining results, collagen type IV appears earlier around the spiral arteries of the decidualized sheath and may be involved in arterial remodeling.…”

The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature

“…Embryo implantation constitutes one of the most vital steps for human reproduction [33]. Implantation is the end-point of a complex cellular and molecular dialogue between two distinct components, namely a viable good-quality embryo characterized by a high developmental dynamic and a properly primed and receptive endometrium [34]. One of the most significant categories of molecules regulating this complex dialogue is the several cytokines that are secreted from different types of cells located in the embryo-maternal interface throughout pregnancy.…”

Immune Tolerance of Embryo Implantation and Pregnancy: The Role of Human Decidual Stromal Cell- and Embryonic-Derived Extracellular Vesicles

“…Functional embryo–maternal interactions occur during embryo implantation and placentation, contributing to a successful pregnancy [ 64 ]. Embryo implantation is a vital step in the complex embryo–maternal interactions, indicating that a well-ready and receptive endometrium recognizes and tolerates a good-quality embryo [ 65 ]. Cytokines released from the endometrium regulate these complex embryo–maternal interactions throughout pregnancy as the immunoregulatory roles in decidualization and placentation [ 66 ].…”