Endometriosis is a persistent and often debilitating condition that impacts over 190 million women globally. This occurs when tissue similar to the uterine lining, known as the endometrium, develops outside the uterine cavity. These abnormal formations, referred to as endometriotic lesions, may attach to various organs such as the fallopian tubes, ovaries, bladder, and intestines, leading to chronic pelvic pain, severe menstrual cramps, and infertility. Despite its considerable implications for women’s health, research on endometriosis suffers from a lack of funding and attention, leaving patients with restricted treatment options and no definitive cure.
The insufficient funding for research is both disheartening and perplexing, given the widespread nature of the disease and the significant burden it imposes on individuals and healthcare systems.
Recently, an innovative method for exploring reproductive health has emerged: endometrial organoids. These miniature, three-dimensional (3D) cell cultures are cultivated from patient tissues to authentically recreate the natural configuration and function of the endometrium. These organoids can also be utilized to model endometriosis, offering insights into the condition’s biological mechanisms and potential drug targets. Dr. Emma Laporte, a postdoctoral researcher at KU Leuven in the Hugo Vankelecom laboratory, is one scientist at the forefront of this research.
“We have observed a pressing need for additional research. It’s astonishing to realize how underfunded women’s health is overall, and as a consequence, how insufficiently studied endometriosis is,” Laporte shared with Technology Networks during an interview at WORD+ 2025.
As researchers continue to deepen our understanding of endometriosis and other gynecological conditions, these advanced models present renewed hope for women worldwide.
Understanding Endometrial Organoids
Organoids are 3D cell structures that closely emulate the nature and function of actual human tissues. Unlike conventional two-dimensional (2D) cell cultures that grow in flat layers, organoids self-organize into 3D structures that more accurately replicate the characteristics of living tissues.
Particularly promising in women’s health research, the organoids developed in Vankelecom’s lab are derived from endometrial biopsies—small uterine tissue samples. These cells are embedded in a specialized gel that simulates the extracellular matrix found in living tissues.
“Endometrial organoids are 3D structures grown in vitro from a single cell, which then self-assemble into organoid formations representing the epithelial layer of the tissue,” explained Laporte.
The endometrium naturally fluctuates in response to the female reproductive hormones estradiol and progesterone, which regulate the cyclical growth, shedding, and regeneration of the uterine lining during the menstrual cycle.
Estradiol
A form of estrogen produced by the ovaries, crucial for regulating the menstrual cycle and supporting reproductive health.
Progesterone
A hormone secreted by the ovaries post-ovulation that prepares the uterus for embryo implantation and sustains it if implantation occurs.
“We can replicate the menstrual cycle within our organoid cultures by providing the appropriate hormones at specific intervals,” said Laporte. “We implement a timed hormonal exposure regime that allows us to observe the menstrual transformations that occur in the endometrium, reflected accurately in the organoids.”
The shift from traditional cell cultures to 3D organoid models marks a significant advancement in studying endometriosis and related conditions. Traditional 2D cell cultures do not capture the structural complexity and cellular interactions inherent in living tissues. In contrast, organoids cultivated in matrix gel more faithfully resemble the original tissue and maintain the 3D environment essential for realistic experimentation.
“I believe 3D cell models better replicate the original tissue compared to traditional 2D cultures,” Laporte noted.
Utilizing Organoids to Investigate Endometriosis
Organoids are establishing themselves as an invaluable resource for studying the underlying biology of endometriosis and identifying potential drug targets. A notable application is seen in the CurE-me Project, which strives to tackle the lack of effective treatments for endometriosis using organoids to generate new therapeutics.
“CurE-me is a collaborative initiative between the BioInnovation Institute in Copenhagen and KU Leuven, aiming to transform endometriosis treatment,” Laporte explained. “We utilize the biobank of endometriosis patient-derived organoids we have established in Leuven to screen drug candidates and create new therapeutics, following the complete spectrum of the drug discovery process from target identification to lead optimization.”
This project uniquely employs organoids derived from both normal endometrial tissues and ectopic lesions associated with endometriosis, allowing researchers to observe the different responses of these tissue types to various treatments.
“We find that ectopic lesion-derived organoids differ significantly from control organoids, and we are now incorporating these endometriotic organoids into our drug discovery efforts,” Laporte stated.
By integrating organoids at multiple phases of the drug discovery process, the project aims to enhance the identification and optimization of potential treatments, effectively bridging the gap between laboratory research and clinical practice through more accurate disease models.
Exploring Further Applications of Endometrial Organoids
Endometrial organoids are also making significant contributions to the understanding of infertility and gynecological cancers.
She and her team have developed implantation models that replicate the dynamics between embryos and the endometrium. In these models, organoids are adjusted to ensure that the apical side faces outward, facilitating direct interaction with stem cell-derived embryo models called blastoids.
Apical Side
The cell surface facing the lumen or external environment, crucial for cellular interactions.
Blastoids
Lab-cultured 3D structures derived from stem cells that simulate early-stage embryos for studying implantation.
These implantation models indicate significant differences between the endometrium mimics from healthy women and those with endometriosis. Notably, embryo attachment rates are lower in endometriosis-derived mimics than in healthy ones, suggesting that the dysfunctional endometrial behavior in endometriosis may inherently reduce the chances of successful implantation.
Beyond fertility research, endometrial organoids are also being applied in cancer investigations.
“We not only create endometrial organoids from healthy individuals and those with endometriosis, but we also work with organoids derived from endometrial cancer patients,” Laporte stated.
“Endometrial cancer is the most prevalent gynecological malignancy, with an increasing incidence and mortality rate. It is characterized by a high recurrence rate, which is why we aim to use endometrial cancer organoids to discover therapeutic targets,” she added.
By cultivating organoids from varied tumor grades, researchers can examine distinct morphological and genetic characteristics closely reflecting the original tumor tissues. These models maintain the genetic variations of primary tumors, proving to be powerful tools in tumor biology research and the identification of potential therapeutic targets.
Industry Adoption and Future Prospects
As research advances, endometrial models have the potential to lead to more personalized and effective treatments, ultimately enhancing outcomes for women affected by these challenging conditions. While there remains ample work to be done before these models see widespread use in clinical research, select biopharma companies have already begun to integrate organoids into their practices. “It’s truly exciting to see that companies are starting to harness these technologies in their laboratories,” Laporte remarked.
