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  • Review Article
  • Published:

Strategies for modelling endometrial diseases

Nature Reviews Endocrinology volume 18, pages 727–743 (2022)Cite this article

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Abstract

Each month during a woman’s reproductive years, the endometrium undergoes vast changes to prepare for a potential pregnancy. Diseases of the endometrium arise for numerous reasons, many of which remain unknown. These endometrial diseases, including endometriosis, adenomyosis, endometrial cancer and Asherman syndrome, affect many women, with an overall lack of efficient or permanent treatment solutions. The challenge lies in understanding the complexity of the endometrium and the extensive changes, orchestrated by ovarian hormones, that occur in multiple cell types over the period of the menstrual cycle. Appropriate model systems that closely mimic the architecture and function of the endometrium and its diseases are needed. The emergence of organoid technology using human cells is enabling a revolution in modelling the endometrium in vitro. The goal of this Review is to provide a focused reference for new models to study the diseases of the endometrium. We provide perspectives on the power of new and emerging models, from organoids to microfluidics, which have opened up a new frontier for studying endometrial diseases.

Key points

  • Endometrial diseases, including Asherman syndrome, endometriosis, adenomyosis and endometrial cancer, represent a major health burden in reproductive-age women and do not have effective therapies.

  • Traditional in vitro culture techniques have long been used to study endometrial diseases, but they are limited by using single cell types and static cultures.

  • Emerging technologies, such as organoids and microphysiological systems, are physiologically relevant and can reproduce many characteristics of native tissues and disease states.

  • Although multiple microphysiological systems that model the endometrium have been developed, most of these have not yet been applied to endometrial diseases.

  • Further innovations in organoid and microfluidic models will enable more accurate endometrial disease modelling and drug testing.

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Fig. 1: The human endometrium and its most common pathologies.
Fig. 2: In vitro models of endometrial diseases.
Fig. 3: Current approaches to model the endometrial niche and pathologies using microfluidic technologies.
Fig. 4: Idealized design of MPS of the healthy endometrium and its diseases.

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  1. Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA

    Alina R. Murphy, Hannes Campo & J. Julie Kim

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Glossary

Organoids

3D cellular aggregates that self-assemble and form structural units that partially resemble the organ in both structure and function.

Microphysiological systems

Integrative, microfabricated platforms designed to recapitulate functional units of human organs in vitro; also known as organ-on-a-chip technology.

Thermoplastics

A class of polymer that can be permanently deformed through the application of heat.

Curettage

Scraping or removal of endometrial tissue for diagnostic or therapeutic purposes.

Spheroids

3D, simple clusters of cells that lack self-assembly or organization.

Sampson’s retrograde menstruation theory

Theory to explain the aetiology of endometriosis in which retrograde flow of sloughed endometrial cells during menstruation occurs through the fallopian tubes into the pelvic cavity promoting the establishment of ectopic lesions.

Chorioallantoic membrane

(CAM). A membrane in bird eggs that is the site of gas exchange for the embryo.

Transwell

A commercially available Boyden chamber device with a microporous membrane that inserts into a standard cell culture well and provides a second compartment.

Micropatterned

Seeding and controlling the geometry and location of cells at the microscale level.

Müllerian remnants

Pluripotent remains of the embryonic precursor to the uterus, which could undergo metaplasia into endometrial tissue during the development of adenomyosis.

Biobanking

Creating a repository of biological samples for use in future research.

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Murphy, A.R., Campo, H. & Kim, J.J. Strategies for modelling endometrial diseases. Nat Rev Endocrinol 18, 727–743 (2022). https://doi.org/10.1038/s41574-022-00725-z

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