Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1-Alpha in Endometriosis: Expression, Regulation, and Potential Role

Objective: The present study was designed to comprehensively analyze the expression profiles of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), estrogen-related receptor-α (ERRα), estrogen receptor-β (ERβ), interleukin-6 (IL-6), cysteinyl-aspartic acid-specific protease-3 (caspase-3), and cysteinyl-aspartic acid-specific protease-9 (caspase-9) in endometriosis tissues. It also aimed to elucidate the hitherto unclarified role of PGC-1α in the processes of proliferation, apoptosis, and gene expression regulation of human endometrial stromal cells, thereby providing novel insights and identifying potential molecular targets for advancing endometriosis treatment modalities.

Methods: A total of 49 ectopic endometrial tissue samples and 50 normal endometrial tissue samples were meticulously collected from patients who underwent gynecological surgeries in the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine in Fuzhou, China, between January 2022 and January 2023. Immunohistochemistry was used to detect protein expression levels. Human primary endometrial stromal cells were transfected and grouped for in-depth analysis. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure gene expression, the cell counting kit 8 (CCK-8) assay was employed to evaluate cell proliferation, and the lactate dehydrogenase (LDH) method was used to determine cell death.

Results: In endometriosis tissues, compared with normal endometrial tissues, the expression levels of PGC-1α, ERRα, and IL-6 were significantly increased. The expression of ERβ was also elevated, while the expression levels of caspase-3 and caspase-9 were decreased. In cell experiments, after transfection with interference plasmids to reduce PGC-1α expression, the expression levels of ERRα and ERβ were decreased, the expression of IL-6 was increased, and the expression levels of caspase-3 and caspase-9 were augmented. Conversely, after transfection with overexpression plasmids to enhance PGC-1α expression, the expression levels of ERRα and ERβ were elevated, the expression of IL-6 was diminished, and the expression levels of caspase-3 and caspase-9 were decreased. Moreover, when PGC-1α expression was interfered with by siRNA, cell proliferation was attenuated (albeit not statistically significant), and cell apoptosis was enhanced. Overexpression of PGC-1α promoted cell proliferation and inhibited cell apoptosis.

Conclusion: PGC-1α potentially plays a crucial role in the pathogenesis of endometriosis by regulating ERRα, ERβ, IL-6, and apoptosis-related factors. This study provides a strong theoretical foundation and a novel direction for developing endometriosis treatment strategies. To the best of our knowledge, it is the first to systematically explore the relationship between PGC-1α and these key factors in endometriosis, filling a knowledge gap. Future studies are needed to further dissect its mechanism and realize its clinical application potential.