A groundbreaking study has successfully constructed organoid models of ovarian endometriosis, providing new insights on the impact of estrogen and progesterone on this prevalent gynecological disease. Endometriosis, which affects millions of women worldwide, poses significant challenges due to its complex biological mechanisms and the varied efficacy of existing treatments.
The research, conducted at the General Hospital of Ningxia Medical University, details the construction of these organoid models, which were developed from the endometrial tissues of patients diagnosed with ovarian endometriosis. The primary goal is to create reliable in vitro models to study disease pathogenesis and test potential treatments more effectively.
Endometriosis is characterized by the presence of endometrial-like tissue outside the uterus, leading to chronic pelvic pain and infertility. With approximately 80% of patients experiencing ovarian endometriosis, traditional models—including two-dimensional cell lines and animal studies—have proven inadequate due to their inability to accurately reflect the human condition and hormonal responses. The establishment of organoids, which are three-dimensional cell structures mimicking the architecture of original tissues, aims to bridge this gap.
Researchers used fresh eutopic and ectopic endometrial tissues collected from 24 patients to develop these organoid models. Following culture, the organoids demonstrated structures similar to normal endometrial tissue, exhibiting key morphological features and maintaining histopathological characteristics.
Immunofluorescence studies confirmed the expression of epithelial markers and hormonal receptors for estrogen and progesterone, emphasizing how the organoids can replicate key biological functions of endometrial tissue. Ruiqi Zhang, one of the authors, noted, "The successful construction of ectopic endometrial organoids provides a new in vitro model for drug intervention and mechanism study of ovarian endometriosis." The match between organoid genetic profiles and original tissues was found to be 100%, underscoring their reliability as models.
Given the roles of estrogen and progesterone in the development of endometriosis, the researchers explored how varying hormone concentrations influenced the proliferation and vitality of the organoids. Their findings revealed intriguing results; lower concentrations of estrogen (5-10 μM) enhanced organoid growth and viability, whereas higher concentrations inhibited proliferation. The data presented showed how the organoids reacted distinctly to hormonal changes, with higher levels of estrogen leading to significantly varied cellular effects.
Meanwhile, the inclusion of progesterone treatments yielded different responses. Experimental observations indicated increased apoptosis within organoids exposed to high concentrations of progesterone, highlighting the delicate balance of hormonal impacts on endometrial tissue.
Commenting on these insights, the authors emphasized, "Both EUT-O and ECT-O could be cryopreserved and revived, allowing for continuous passaging with no significant morphological changes." This ability to rejuvenate organoids offers vast potentials for long-term studies and the development of personalized medicine approaches for endometriosis treatment.
Notably, the organoids appear to mimic the clinical variability seen among patients, thereby presenting opportunities to tailor individualized treatments based on specific hormonal sensitivities. The research signifies not only the potential of organoids as powerful tools for biological research and treatment development but also emphasizes the complexity of managing endometriosis due to its multifaceted nature.
Concluding the study, the authors suggest, "These organoids could serve as reliable research models and have now been proven as stable cell models in the study of tumors." The findings present compelling evidence for the application of organoid models within the area of gynecological health, paving the way for more effective interventions and personalized care strategies for endometriosis patients.