Endometrial Organoids Are Advancing Women’s Health

Endometriosis is a chronic and often debilitating condition that affects over 190 million women worldwide. It occurs when tissue similar to the lining of the uterus, called the endometrium, grows outside the uterine cavity. These abnormal growths, known as endometriotic lesions, can attach to various organs including the fallopian tubes, ovaries, bladder and intestines, causing chronic pelvic pain, intense menstrual cramps and infertility. Despite its significant impact on women’s health, endometriosis research remains underfunded and undervalued, leaving patients with limited treatment options and no definitive cure.

This lack of research funding is not only disheartening but also perplexing, given the disease’s prevalence and the profound toll it takes on individuals and healthcare systems.

Continue reading below...

News

Endometriosis: What’s the Latest Research?

Read more

Recently, a new approach to studying reproductive health emerged – endometrial organoids. These tiny, three-dimensional (3D) cell cultures are developed from patient tissues to closely mimic the natural configuration and biology of the endometrium. These organoids can also be used to model endometriosis and provide insights into the condition’s pathobiological underpinnings and potential drug targets.  One scientist working in this field is Dr. Emma Laporte, a postdoctoral researcher at KU Leuven  in the Hugo Vankelecom laboratory.

“We really noticed that there was a need for more research. It's crazy if you think about how underfunded the womens’ health domain is in general, and then, as a result, how under-researched endometriosis is,” Laporte told Technology Networks, in an interview during WORD+ 2025.

As scientists work to further understand endometriosis and other gynecological conditions, these advanced models offer renewed hope for women around the world.

What are endometrial organoids?

Organoids are cultured 3D cell configurations that closely mimic the nature and function of real human tissues. Unlike traditional two-dimensional (2D) cell cultures, which grow as flat sheets of cells on a petri dish, organoids self-assemble into 3D structures that more accurately replicate the original living tissues.

Endometrial organoids are particularly promising in the field of women’s health research. The organoids from Vankelecom’s lab are derived from endometrial biopsies – small samples of uterine tissue obtained from patients. The cells from these biopsies are embedded in a specialized gel, which mimics the extracellular matrix of living tissues.

"Endometrial organoids are 3D structures that are grown in vitro. They start from a single cell, and then they can self-assemble to form the organoid structures. Tissue-derived organoids represent the epithelial compartment of the tissue," said Laporte.

The endometrium naturally changes in response to the female reproductive hormones estradiol and progesterone. These hormones regulate the cyclical growth, shedding and regeneration of the uterine lining, as occurs during the menstrual cycle.

"We can mimic this [the menstrual cycle]  in our organoid cultures by supplying the correct hormones to the culture," said Laporte. “We have a timed hormonal exposure schedule in which we add the correct hormones and factors at specific timepoints to our culture to mimic the menstrual cycle. We can now see the menstrual changes that occur in the endometrium in vivo in the organoids in the dish.”

The transition from traditional cell cultures to 3D organoid models represents a notable shift in the study of endometriosis and related conditions. Traditional 2D cell cultures lack the structural organization and cellular interactions that characterize living tissues. In contrast, organoids grown in a matrix gel more accurately resemble the original tissue and maintain the 3D environment that is essential for realistic experimentation.

"I think 3D cell models resemble the original tissue better than you would have in traditional 2D cell cultures," said Laporte.

Using organoids to study endometriosis

Organoids are proving to be a valuable tool in studying the pathobiology of endometriosis and identifying potential drug targets. One of the most promising applications of organoids is demonstrated in the CurE-me Project, which aims to address the lack of effective treatments for endometriosis by using organoids to develop new therapeutics.

"CurE-me is a collaborative project between the BioInnovation Institute  in Copenhagen and KU Leuven, in which we want to revolutionize endometriosis treatment,” Laporte explained. “We use the biobank of our endometriosis patient-derived organoids that we have established in Leuven to screen drug candidates and develop new therapeutics. We want to use the organoids in several steps of the drug discovery process, starting from target identification and validation all the way through to lead optimization."

One of the unique features of this project is the use of organoids derived from both control endometrium (normal, healthy endometrial tissue) and ectopic lesions (endometrial tissue that grows outside the uterus, characteristic of endometriosis). These organoids help researchers study how the different tissue types respond to various treatments.

"We see that these ectopic lesion-derived organoids are very distinct from the control organoids, and we are now using these endometriotic organoids in the drug discovery project," Laporte said.

By incorporating organoids at several stages of the drug discovery process, the project aims to streamline the identification and optimization of potential treatments. This approach helps to bridge the gap between laboratory research and clinical application by providing more accurate models of the disease.

Other applications of endometrial organoids

Endometrial organoids are also proving useful in understanding infertility and gynecological cancers.

“There are a lot of fertility issues associated with endometriosis,” Laporte said.

Laporte and her colleauges have developed implantation models that mimic the interaction between embryos and the endometrium. In these models, the organoids are manipulated to ensure the apical side faces outward, creating a surface that can interact directly with stem cell-derived embryo models, known as blastoids.

These implantation models revealed  notable differences between the endometrium mimics of healthy women and of women with endometriosis. One key finding was that embryo attachment rates are lower in endometriosis-derived endometrial mimics compared to healthy controls, suggesting that aberrant endometrial functioning in endometriosis may inherently hinder successful implantation.

Beyond fertility studies, endometrial organoids are also being used in cancer research.

“We don't only create endometrial organoids from healthy individuals and endometriosis patients, but we also have endometrial cancer-derived organoids,” said Laporte.

“Endometrial cancer is the most common gynecological malignancy. There is a rising incidence and rising mortality. It is characterized by high recurrence and that's why we want to use endometrial cancer organoids to find therapeutic targets,” Laporte said.

By cultivating organoids from different tumor grades, the researchers can observe distinct morphological and genetic profiles that closely mirror the original tumor tissues. These models maintain the copy number variations of the primary tumors, making them powerful tools for studying tumor biology and identifying potential therapeutic targets.

Industry adoption and future directions

As research progresses, endometrial models may lead to more personalized and effective treatments, improving outcomes for women affected by these challenging conditions. Although there is more work to be done until we see these models used widely in clinical research, some biopharma companies are already starting to incorporate organoids into their work, Laporte said: “It’s really cool to see that companies are already adopting all these technologies in their labs.”