The long-term objectives of this application are to identify sites and mechanisms of action of vitamin D that are responsible for the reduced fertility observed in vitamin D deficiency. That normal reproductive functions are vitamin D-dependent was a novel finding with direct implications for human fertility. Reproductive studies in vitamin D- deficient rats will identify vitamin D-dependent targets that directly affect fertility. The role of fertility factors in mammals are especially important to developments that improve human fertility. The current application will test the hypothesis that the infertility of vitamin D deficiency is a result of perturbation of androgen synthesis and action in reproductive tissues.
The specific aims are: 1) to determine if androgen synthesis is altered by measuring circulating concentrations of testosterone (T), 2) if circulating T concentrations are low in vitamin D-deficient animals, stimulation of T synthesis with human chorionic gonadotropin infusions and the restoration of normal fertility with T implants will be attempted, 3) to determine if vitamin D deficiency is interfering with androgen sensitive mechanisms associated with spermatogenesis and sperm maturation, androgen-binding protein (ABP), a Sertoli cell product and marker of androgen action, will be measured in testes and epididymides, and 4) since Sertoli cells are a target for vitamin D, testicular histomorphometric evaluation will be accomplished in vitamin D-deficient animals in conjunction with studies of sperm production rates, morphology, viability, and motility. Students will be employed and encouraged to participate in data generation and analyses. This will provide """"""""hands-on"""""""" research experience for several undergraduate students. Such participation and training is advantageous for furthering undergraduate experiences and careers in the biomedical research sciences.
