Molecular Characterization of Ovarian Endometriosis in Saudi Arabian Women: Insights into Inflammatory, Autophagic, and Epigenetic Dysregulation

Ovarian endometriosis (OE) is a chronic, inflammatory gynecological disorder associated with sterility and an elevated risk of ovarian cancer. Despite its high prevalence, the complex molecular mechanisms governing OE pathogenesis remain poorly investigated. We conducted a comprehensive histopathological and molecular investigation of OE in a cohort of 188 Saudi women (88 patients with OE and 100 healthy controls) using histopathological, qRT-PCR, immunostaining, and Western blot techniques. Histopathological analysis confirmed significant stromal fibrosis and chronic inflammation in endometriotic lesions. Gene expression profiling revealed a pro-proliferative, anti-apoptotic signature, marked by the upregulation of PTTG1 and the downregulation of TNFRSF10D, CDK4, and CDKN1A. Interestingly, we identified a post-transcriptional regulatory paradox in the inflammatory response: while IL-6 mRNA was significantly upregulated, its corresponding protein level was downregulated, suggesting a novel, tightly controlled mechanism to limit excessive local inflammation. Besides the increased autophagic activity and decreased Ubiquitin mRNA levels, epigenetic dysregulation was prominent, characterized by the upregulation of DNA methyltransferase DNMT3B and the downregulation of the histone variant H3.1. These findings elucidate novel molecular pathways underlying OE pathogenesis as evidenced by a post-transcriptional paradox in IL-6 expression, and uncover key dysregulations spanning cell proliferation, apoptosis, inflammation, autophagy, and epigenetic regulation.