Date of Award

8-1-2016

Degree Name

Master of Science

Department

Molecular Biology Microbiology and Biochemistry

First Advisor

Braundmeier, Andrea

Abstract

Chronic inflammation is associated with a dysregulation of the immune response. Inflammation is also associated with decreased reproductive capacity in women, however an exact mechanism has yet to be identified. Physiological states such as obesity and disease states such as endometriosis are both associated with chronic inflammation, an insufficient immune response, and infertility in women; therefore these two conditions serve as excellent models to study the effects of inflammation on reproductive function. Early indications of inflammation may aid in early detection of immune dysregulation associated with different physiological and pathological conditions. One way to measure immune balance between pro- and anti-inflammatory states in the female urogenital tract is by observing changes in the bacterial species that populate the mucosal surface. Commensal bacteria that make up the microbiome play a critical role in the development and maturation of the immune system in humans. Because these microbes and the host’s immune system are constantly influencing each other, several immunological conditions and disease states have been shown to have an altered microbial profile than that of healthy individuals. The goal for this study was to examine how triggers of inflammation alter the peripheral immune response, urogenital microbial communities, and reproductive function. Specifically, our aims were to 1) use an animal model of obesity to determine whether this physiological model of inflammation decreases immune protection of the urogenital microbiome and alters ovarian function; and 2) use endometriosis as a disease model of inflammation to assess whether the presence of endometriotic lesions alters urogenital microbial dynamics, and also whether surgical intervention restores commensal bacterial profiles to that of a non-disease state. The results of this study revealed that the urogenital microbial community dynamics were altered in both our obese and disease models of inflammation compared to their respective controls. In the obesity study, we also found that our obese model had decreased markers of inflammation, which may be due to dietary composition. In the endometriosis study, we observed that patients with disease had a unique urogenital microbiome profile and that surgery had an effect in shifting the urogenital microbial profiles of several patients. Overall, our long-term goal is to determine whether the urogenital microbiome is a good indicator of immune stress and if alternative therapies can alter microbial community dynamics, eliminate immune stress associated with disease. Ultimately we are looking at the microbiome as an indicator of overall immune health and implementing alternative diagnostic and treatment strategies to immune diseases that affect reproductive function in women.

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