The underlying hypothesis of this proposal is that a decrease in antioxidant status of the developing follicle results in abnormal follicular and oocyte function whereas antioxidant depletion is necessary for the sequelae induced by LH that induces ovulation, and the resumption of meiosis. This hypothesis is based largely upon observations in ascorbic acid-deficient animals of follicular atresia and oocyte malfunctions. The studies described herein will investigate ascorbate as the preeminent antioxidant and its role in follicle development. Using several well-established rat models and both in vivo and in vitro cell culture experiments, kinetic analyses of ascorbate uptake will be investigated in granulosa and theca cells, and cumulus enclosed and denuded oocytes. The regulatory endocrine factors governing uptake will be identified. Antioxidant levels present in developing follicles, during ovulation and in atresia will be determined. The role of ascorbic acid in the responsiveness of follicles to gonadotropins and in the inhibition of meiosis will be determined. The hypothesis that cell secretion as a mechanism underlying follicular ascorbate depletion will be tested and the endocrine factors and pathologic conditions which regulate secretion will be determined. Lastly, the origins, nature, and regulation of follicular reactive oxygen species will be determined.
| Behrman, H R; Kodaman, P H; Preston, S L et al. (2001) Oxidative stress and the ovary. J Soc Gynecol Investig 8:S40-2 |
| Kodaman, P H; Behrman, H R (2001) Endocrine-regulated and protein kinase C-dependent generation of superoxide by rat preovulatory follicles. Endocrinology 142:687-93 |
| Guarnaccia, M M; Takami, M; Jones, E E et al. (2000) Luteinizing hormone depletes ascorbic acid in preovulatory follicles. Fertil Steril 74:959-63 |
| Kodaman, P H; Behrman, H R (1999) Hormone-regulated and glucose-sensitive transport of dehydroascorbic acid in immature rat granulosa cells. Endocrinology 140:3659-65 |
| Zreik, T G; Kodaman, P H; Jones, E E et al. (1999) Identification and characterization of an ascorbic acid transporter in human granulosa-lutein cells. Mol Hum Reprod 5:299-302 |
