The aim of this proposal is to examine ovarian aging in the baboon (Papio) with the goal of establishing this model for future studies of the premenopausal-menopausal transition. The hypothesis is that the adult female baboon reaches menopause in a physiologically similar manner to the human female. Thus in this pilot proposal baseline data will be obtained to determine if plasma hormone profiles and follicle dynamics in the baboon are similar to the human female. This data will establish whether the baboon can be used in future studies that are not readily feasible in the human. The baboon population to be examined is based at the Southwest Foundation for Biomedical Research (SWFBR). A cohort of pedigreed females will be divided into groups of five according to chronological age representing, i) adults at peak fertility (age 6- 12 years) (Group A) ii) pre-menopausal, (age 13-22 years) (Group B), and iii) menopausal (age 23-30 years) (Group C).
Two aims are proposed.
Aim 1 : Characterization of the menstrual cycle will involve an examination of i) perineal tumescence to determine menstrual cycle length through 10 cycles and ii) hormone profiles (daily samples from two menstrual cycles) which will indicate ovarian-pituitary activity. Thus hormone analyses will include assays of estrone, estradiol, progesterone, testosterone (total and free), androstenedione, luteinizing hormone, follicle stimulating hormone, insulin-like growth factor 1 and insulin-like growth factor 1 binding protein, the two isoforms of inhibin (inhibin-A and inhibin-B) and sex hormone binding globulin (SHBG).
Aim 2 i) Characterization of the follicle population using i) histological sections and analysis of the rate of depletion of non-growing and growing follicles by mathematical models, ii) determination of atresia using DNA fragmentation determination in histological sections, and iii) immunohistological localization of bcl-2 and p53, two factors that have opposing actions in the process of apoptosis. Data will be obtained and statistical analysis of each parameter with comparisons between groups will be performed. Preliminary data suggests a close similarity in the process of reproductive senescence between the human female and the baboon. The data will be the basis of future in vivo and in vitro studies. The studies will be integrated with studies of osteoporosis, cardiovascular and psychosocial changes occurring during the premenopausal and post- menopausal years in the baboon, which are ongoing at the SWFBR. Future studies will also examine uterine, adrenal, thyroid, pineal, pituitary and hypothalamic aging.
