ALTERATION OF CYTOCHROME P450 GENE EXPRESSION AND MICROBIAL PROFILES IN PATIENTS WITH ENDOMETRIOSIS

Author

Han Do, Southern Illinois University CarbondaleFollow

Date of Award

12-1-2023

Degree Name

Master of Science

Department

Molecular Biology Microbiology and Biochemistry

First Advisor

Braundmeier-Fleming, Andrea

Abstract

Endometriosis is characterized by aberrant estrogen signaling and chronic inflammation that results in prolonged pelvic pain and infertility. Research from our lab along with others have found that the chronic inflammatory state is maintained by a high ratio of inflammatory/ tolerant (Th17/ Tregs) cells systemically as well as increased Treg localization (tolerance) within endometriotic lesions, allowing endometriotic lesions to escape effector immune clearance. Moreover, this phenotype creates an intolerant environment for successful implantation which poses a risk of infertility and pre-term delivery in this group of women. Our previous research has also found that women with endometriosis have microbial dysbiosis within both gastrointestinal and urogenital (GI/UG) environments that may contribute to abnormal metabolism of parent estrogens. We hypothesized that microbial disruption alters enterohepatic recirculation of endogenous hormones by changing expression of cytochrome P450 (CYPs) enzymes that metabolize parent estrogens. Along with presence of disease, many external factors might also contribute to microbial disruption within the urogenital environment such as sexual partner encounters. Surgical intervention and use of hormonal therapies for treatment of endometriosis, may also contribute to microbial composition within the GI and UG environments in diseased patients. Our goal for this study was to 1) measure several CYP enzyme gene expressions in both eutopic endometrium and ectopic endometriotic lesions of diseased subjects; and 2) investigate the association of sexual partner number on microbial profiles in vaginal, urine and fecal samples of diseased patients, and whether hormonal therapy and surgical intervention affect microbial dynamics within the GI and UG environments. Our data showed that CYP1B1 gene expression was altered in eutopic endometrium of diseased patients. Hormonal therapy (HT) increased CYP1B1 gene expression in both eutopic and ectopic endometrial tissue. Patients who had more than 7 sexual partners had increased microbial dysbiosis indicated by increased composition of anaerobic bacteria in fecal and vaginal samples, indicating that increased number of sexual partners further altered microbial dysbiosis in patients with endometriosis. In conclusion, our long-term goal is to identify a unique microbiome that may serve as a potential marker to detect the early onset of endometriosis. Our study contributes to current knowledge on the expression of CYP enzyme metabolites on endometriosis. Since our patient cohorts are divided based on hormonal and surgical treatment, we hope to contribute additional knowledge on the impact of pharmacological and surgical therapy on the expression of CYP enzymes in endometriosis. Moreover, we hope to gain more understanding about mechanisms that cause alteration of CYPs gene expression in patients with endometriosis. Understanding the pathophysiology of endometriosis is critical for advancement of novel therapeutic targets and treatment of disease. Through investigation of a patient’s immune system, endocrine regulation and microbial profiling, we hope to advance our understanding of the disease and identify potential areas for improving diagnostics and therapeutic interventions.