Resveratrol and Its Natural Analogs Mitigate Immune Dysregulation and Oxidative Imbalance in the Endometriosis Niche Simulated in a Co-Culture System of Endometriotic Cells and Macrophages.

Inflammation and immune cell dysfunction are critical facilitators of endometriosis pathophysiology. Macrophages are renowned for stimulating lesion growth, vascularization, innervation, and pain generation. By combining macrophages and endometriotic cells, we determined if resveratrol and its natural analogs can target the immune dysregulation and oxidative imbalance in endometriosis.

Natural resveratrol analogs differentially target endometriotic cells into apoptosis pathways.

The specific characteristics of endometriotic cells are their ability to evade the apoptotic machinery and abnormal response to apoptotic stimuli. Natural-originated compounds may constitute a beneficial strategy in apoptosis modulation in endometriosis. We investigated and compared the potency of natural resveratrol analogs, including piceatannol, polydatin, and pterostilbene, in targeting cell death pathways, including apoptosis-related morphologic and biochemical processes, alongside the modulation of the critical genes expression.

In vitro modeling of endometriosis and endometriotic microenvironment - Challenges and recent advances.

Endometriosis is a chronic condition with high prevalence in reproductive age women, defined as the growth of endometrial tissue outside the uterine cavity, most commonly on the pelvic peritoneum. The ectopic endometrial lesions exist in a unique microenvironment created by the interaction of epithelial, stromal, endothelial, glandular, and immune cell components, dominated by inflammatory, angiogenic, and endocrine signals. Current research is directed at understanding the complex microenvironment of the lesions and its relationship with different endometriosis stages, phenotypes, and disease symptoms and at the development of novel diagnostic and therapeutic concepts that minimalize the undesirable side effects of current medical management.