Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services,

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... torate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACT Menopause is defined as a permanent cessation of menstruation resulting from depletion of germs cells and loss of ovarian follicular activity. Menopausal ovaries undergo morphological changes that are likely related to the increased incidence of ovarian cancer in the peri-and post-menopausal periods. The germ cell-deficient Wv mice recapitulate these post-menopausal alterations in ovarian morphology and develop tubular adenomas. Genetic deletion of cyclooxygenase 1 (COX-1) delays germ cell depletion and preserves ovarian follicles and substantially delays the tumor development. Pharmacological inhibitors of COX-1 also rescued the tumor phenotype and preserved primary follicles in aged mice. These findings suggest that COX-1 activity may contribute to preneoplastic morphological changes of the ovarian surface epithelium, which can potentially be prevented by pharmacological inhibitors of COX-1. Moreover, the observations indicate that depletion of follicles may underlie the etiological factors that influence ovarian cancer risk. SUBJECT TERMS Ovary, cyclooxygenase-1, tumor, follicle 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c. THIS PAGE U UU 12 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18