Morphometric evaluation of diabetes-associated ovarian atrophy in the C57BL/KsJ mouse: relationship to age and ovarian function.

Progressive, diabetes-associated ovarian atrophy was analyzed in C57BL/KsJ diabetic (db/db) and control (+/?) mice between 2 and 16 weeks of age. Tissue changes were histologically and morphometrically analyzed and compared with ovarian functional indices (i.e., serum estradiol and progesterone) and metabolic (i.e., glucose uptake and estradiol sequestration) parameters. No significant differences were found between the ovarian follicular populations of either group at 2 and 4 weeks of age. However, between 4 and 8 weeks, the ovaries of diabetic mice exhibited marked stromal and follicular degeneration and an associated decline in the population of viable follicles as compared with controls. Between 8 and 16 weeks of age the follicular atrophy in the diabetics became more marked, as compared with controls, with the accumulation of intracellular lipid pools accenting the tissue degeneration and adiposity observed in both follicular and stromal compartments. In addition, ovarian function was depressed after 6 weeks of age in diabetic females as compared with controls as indicated by lowered serum estradiol and progesterone levels. Ovarian glucose uptake was enhanced in diabetic females while the ability of the ovary to sequester radiolabeled estradiol declined between 4 and 16 weeks of age as compared with controls. These data indicate that ovarian dysfunction in the (db/db) mutant mouse is associated with follicular atrophy, adiposity, impaired steroidogenesis, and imbalanced glucose utilization. These events occur in temporal association with the onset and progressive exacerbation of the hyperglycemic condition. It is suggested that ovarian involution in these mutants is directly related to an impaired follicular ability to metabolize properly the elevated intracellular glucose concentrations that develop in the (db/db) mice as compared with controls.