DELLA CORTE, LUIGI (2024) The link between pollution, genomic instability and pelvic pain perception in the pathogenesis of endometriosis: a cross-sectional study. [Tesi di dottorato]

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Abstract

The aim of this PhD project was to evaluate the relationship between environmental pollutants, genomic instability and altered expression of ion channels into the peritoneum of patients affected by stage I-II endometriosis compared to healthy ones. This is a single-center, cross-sectional study that was carried out at University Federico II of Naples, Italy. The study has been approved by the Local Ethics Committee (Protocol Number 06/22 of 12/07/2022). From July 2022 to April 2024, we collected data on 104 patients undergoing laparoscopic surgery for the eradication of both superficial peritoneal endometriosis and endometriomas (Group A= 45) compared to those undergoing laparoscopic surgery for benign adnexal disease (Group B= 59), coming from areas with low or high exposure to EDCs. We evaluated: pain perception through VAS score questionnaire in both groups; the severity of endometriosis-related symptoms and their impact on quality of life in Group A; CA 125 levels on blood exam in both groups; dioxins level on urine test in both groups; TRPV1 expression and MSI evaluation on tissue from peritoneal biopsies of women of both groups. The dioxin levels detected in the urine, while slightly higher in Group A, did not exceed the normal threshold values. CA 125 blood dosage revealed a median concentration statistically significant in the Group A compared to the controls (p<0.05). The MSI status evaluation showed a subset of patients with high microsatellite instability (MSI-H) in the endometriosis group that could be at a higher risk for the development of endometriosis-associated ovarian cancers (EAOCs). A lower expression of TRPV1 receptors in patients with stage I-II endometriosis compared to controls was reported, suggesting a different pathophysiological process of perceived pain in mild forms of endometriosis, potentially influenced by epigenetic and environmental factors, different from data published so far in literature that reports an increased expression of this channel in case of DIE and CPP. Our data highlights the complex interplay between environmental exposure, genomic instability, and pelvic pain perception in such a widespread and still little-known disease as endometriosis.

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