Submission
| Title: | Investigating the Impacts of Estrogen Receptor Alpha (ERα) Deficiency on Dynamics of the Ovarian Immune Microenvironment |
| Presenter: | Lucy Salter |
| Institution: | Indiana University School of Medicine |
| Authors: | Lucy Salter1, Tia Brodeur1,2,3 Indiana University School of Medicine1, Department of Obstetrics and Gynecology2, Division of Reproductive Endocrinology and Infertility3 |
Abstract
| Background/Significance/Rationale: | The ovary is a dynamic reproductive organ with an immune microenvironment that allows for continual remodeling following monthly tissue damage. While it is understood that M1 and M2 macrophages play roles in folliculogenesis and mediating vital cyclic remodeling, the role of natural killer (NK) cells is less characterized. Utilizing an ERα deficient experimental group, this study aims to examine differences in macrophage and NK cell trafficking, inflammation, follicle number, and to novelly elucidate an NK cell role. We hypothesize that ERα deficient tissues will have an influx of macrophages and NK cells and increased inflammation which will impair follicular development. |
| Methods: | ERα deficient mice created utilizing the Cre-Lox system were exposed to 48 hours of exogenous gonadotropins or saline before ovarian cells were isolated for flow cytometric analysis of NK cell activation upon ovarian stimulation. Next, ovarian tissues were sectioned and stained for IHC analysis and quantification of follicle number. Finally, tissues were stained with NK1.1/CD161 or CD206/MRC1 primary antibodies for immunofluorescent evaluation of macrophage and NK cell trafficking. |
| Results/Findings: | Flow cytometry demonstrated that ovarian stimulation led to a significant increase in NK cell activation. Additionally, immunohistochemistry revealed that ERα deficiency led to a significant increase in inflammation. However, ERα deficiency did not lead to defective ovulation, with no significant changes in corpora lutea number, and did not cause deficient follicular development. Finally, immunofluorescence showed that NK cells are present in both ERα deficient and control ovarian tissues with presence mainly surrounding graafian follicles |
| Conclusions/Discussion: | |
| Translational/Human Health Impact: | The results from this study help to better understand the impacts of estrogen on the ovarian immune microenvironment and demonstrate a presence of NK cells in ovarian tissue. Further research looking into distinct patterns of NK activation in specific locations will aim to further elucidate NK role in ovarian disease. |
