Direct vitamin D3 actions on rhesus macaque follicles in three-dimensional culture: assessment of follicle survival, growth, steroid, and antimüllerian hormone production

Objective To investigate the direct actions of active 1,25-dihydroxy vitamin D3 (VD3) upon primate follicular development at specific stages of folliculogenesis. Design Secondary preantral follicles were isolated from rhesus monkeys ovaries, encapsulated in alginate, and cultured for 40 days. Follicles were randomly assigned to experimental groups of control, low-dose VD3 (LVD3; 25 pg/mL), and high-dose VD3 (HVD3; 100 pg/mL). Setting National primate research center. Animal(s) Adult, female rhesus macaques (Macaca mulatta). Intervention(s) None. Main Outcome Measure(s) Follicle survival and growth, as well as oocyte size, were assessed. Progesterone (P₄), androstenedione (A₄), E₂, and antimüllerian hormone (AMH) concentrations in culture media were measured. Result(s) Compared with the control group, LVD3 increased preantral follicle survival at week 2 by >66%, while HVD3 increased antral follicle diameters at week 5. Follicles with diameters ≥500 μm at week 5 were categorized as fast-growing follicles. Higher percentages of fast-growing follicles were obtained after HVD3 treatment. Although P₄, A₄, and E₂ production by antral follicles was not altered by VD3, AMH concentrations were 36% higher in the LVD3 group relative to controls at week 5. Oocytes with larger diameters were retrieved from antral follicles developed in both LVD3 and HVD3 groups compared with controls. Conclusion(s) The addition of LVD3 increased preantral follicle survival and maintained AMH production by antral follicles, while HVD3 improved antral follicle growth. VD3 supplement promoted oocyte growth in in vitro–developed follicles. Direct actions of VD3 on the primate follicle appear to be both dose and stage dependent.