Microphysiological Modeling of the Human Endometrium

Since the beginning of clinical medicine, the human uterus has held the fascination of clinicians and researchers, given its critical role in the reproduction of our species. The endometrial lining provides residence for the embryo; however, this symbiotic interaction can be disrupted if the timing is not correct and the endometrium is not receptive. Diseases associated with the endometrium interfere with the reproductive process and cause a life-altering burden of pain and even death. With the advancement of technologies and new insights into the biology of the endometrium, much has been uncovered about the dynamic and essential changes that need to occur for normal endometrial function, as well as aberrations that lead to endometrial diseases. As expected, the more that is uncovered, the more the complexity of the endometrium is made evident. In this study, we bring together three areas of scientific advancement that remain in their infancy, but which together have the potential to mirror this complexity and enable understanding. Studies on induced pluripotent stem cells, three-dimensional tissue mimics, and microfluidic culture platforms will be reviewed with a focus on the endometrium. These unconventional approaches will provide new perspectives and appreciation for the elegance and complexity of the endometrium. Impact statement The ability of the human endometrium to regenerate on a monthly basis for ∼4 decades of reproductive years exemplifies its complexity as well as its susceptibility to disease. Restrictions on the types of research that can be done in the human endometrium motivate the development of new technologies and model systems. The three areas of technological advancement reviewed here-induced pluripotent stem cells, three-dimensional model systems, and microfluidic culture systems-will highlight some of the tools that can be applied to studying the human endometrium in ways that have not been done before.