Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

December 1994

Abstract

Ovulation has been hypothesized as an inflammatory process. Interleukin(IL)-1$\alpha$, IL-1$\beta$ and tumor necrosis factor(TNF)-$\alpha$ are potent cytokines produced from macrophages and various other cell types, and are pivotal components of inflammation. Although previous studies have investigated cytokine activities in the reproductive system, there is little information on their precise localization and activities during the periovulatory period. To investigate the role of cytokines in ovulation, experiments were designed to determine the immunohistochemical localization and time specific production of cytokines IL-1 and TNF-$\alpha$ using a mouse model at 36h, 12h, 6h, 2h before ovulation, and at 6h and 18h after ovulation in vivo. Isolated individual follicles in vitro were used to determine more precise roles of cytokines on follicular development, ovulation and steroidogenesis. From these studies it was found that (1) granulosa cells were the primary sites of IL-1$\alpha$ and TNF-$\alpha$ production from large antral follicles and preovulatory follicles in vivo, (2) production of IL-1$\alpha$ and TNF-$\alpha$ increased as ovulation neared, first appearing in the cumulus cells and expanding to antral and mural granulosa cells, (3) less intense staining of these cytokines in the theca layer of smaller follicles suggests that theca cells may contribute to the production of these cytokines to some extent, (4) but there was no IL-1$\beta$ production, (5) localized and temporal production of cytokines during the periovulatory period suggests precise regulation, (6) decrease of IL-1$\alpha$ in the ovary after gonadotropin injection determined by enzyme linked immunoadsorbent assay suggests that IL-1$\alpha$ production may be under the control of gonadotropins, (7) in follicle culture without bone marrow derived cells, granulosa cells were confirmed as the main source of cytokine production, (8) addition of IL-1$\alpha$ and TNF-$\alpha$ to follicles in culture tend to decrease estradiol production. In conclusion, immunoreactive cytokine production correlated positively with the periovulatory follicular development suggesting their role as ovulatory mediators. It requires further studies on what are the signals for the initiation and termination of cytokine production, how transcription and translation of these cytokines are regulated during the periovulatory period, and how they contribute to the ovulation.

Document Type

Dissertation - unrestricted

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