This proposal outlines a career development plan for the applicant, a clinically trained obstetrician/gynecologist, who is making the transition from clinician to basic biomedical researcher. The candidate's goals for this award are to learn modern molecular and cellular techniques as applied to his research on female reproductive aging, and to facilitate the final transition to becoming an independent investigator. Under the mentorship of established investigators and a multidisciplinary advisory committee, the candidate will pursue a program of instruction and research that maximizes the likelihood of his developing into an independent scientist. The research proposed seeks to determine how photoperiod and the pineal gland hormone melatonin affect female reproductive aging. The model species is the Siberian hamster (Phodopus sungorus), an easily maintained laboratory animal whose reproductive biology is exquisitely sensitive to day length and melatonin. Rearing female hamsters in a short day photoperiod decelerates reproductive aging. Short day females had significantly greater litter success than age-matched long day females at 9 months of age. Pregnancy failures occurred only in long day females, and maternal and fetal deaths during parturition in this group are consistent with uterine dysfunction. Ovaries from adult short day females had twice as many primordial follicles as ovaries from age-matched long day females.
Three aims are proposed: 1) to determine if the photoperiodic effect on ovarian primordial follicle number is due to a decrease in follicular atresia and/or an increase in follicular renewal; 2) to identify how the hormones and factors that modulate primordial follicle activation are affected by photoperiod and melatonin; and 3) to determine if photoperiod and melatonin modulate the age-associated decline in uterine function by inhibiting cellular senescence, telomere shortening, and attrition of estrogen receptors. The proposed work is relevant to understanding the cellular and molecular mechanisms underlying reproductive aging, and how that process may be decelerated. Once the objectives of this award have been met, the candidate will work as an independent investigator, and carry out research on reproductive aging that is truly integrative.
