Structure and Remodeling of the Endometrium

The uterus is lined by a specialized tissue called the endometrium, which is composed of a layer of epithelial cells and underlying stromal cells. During the course of a woman’s menstrual cycle, the endometrium undergoes a number of changes in preparation for implantation of an embryo and a subsequent pregnancy. These changes include thickening of the endometrium and the formation of new blood vessels, a process called angiogenesis. This is to prepare for development of the placenta, which connects the fetal blood supply to that of the mother, and is formed when the blastocyst (a 5-6-day-old embryo) implants into the endometrium. In particular, the trophoblast, or outer layer of the blastocyst, invades into the endometrium and directs endometrial remodeling (including angiogenesis) to prepare for implantation.

Recent Research in 3D Tissue Engineering Using Lifeline® Endometrial Epithelial Cells

Although it is known that the trophoblast (outer layer of the blastocyst) invades into the endometrium to prepare for embryo implantation, in vitro models of the process are lacking. In a study from this year, Zambuto and colleagues set out to develop a 3D model to study the endometrium and trophoblast, including the processes of endometrial angiogenesis and trophoblast invasion. Using tissue engineering techniques, they developed a hydrogel platform (with methacrylamide-functionalized gelatin [GelMA]) that best mimicked endometrial stiffness with 5 wt% hydrogel. They next co-cultured human umbilical vein endothelial cells (HUVECs) and endometrial stromal cells to confirm that the GelMA hydrogel could support and induce formation of endothelial cell networks, modeling angiogenesis. Next, they evaluated growth and spread of Lifeline® human endometrial epithelial cells on GelMA hydrogels, and found that by 6 hours, cells had attached to the matrix and had begun to spread after 3 days.

In response to progesterone and cAMP, endometrial stromal cells differentiate into decidual cells in preparation for pregnancy. The researchers tested the ability of their 3D platform to support this stromal cell differentiation by treating endometrial stromal cells cultured on GelMA with progesterone and cAMP. They found that these treatments induced cell morphology characteristic of decidual cells and increased production of prolactin and IGFBP-1 (two decidual proteins) over the course of 6 days. Finally, to determine whether their model could be used to study trophoblast invasion, they added trophoblast cells in the form of spheroids to the GelMA hydrogel and observed that over the course of 7 days, cell invasion into the matrix increased.

Together, the results of this study highlight a new model system for studying endometrial dynamics and trophoblast invasion.

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