Diabetes-associated alterations in uterine structure in the C57BL/KsJ mouse: relationship to changes in estradiol accumulation, circulating ovarian steroid levels, and age.

The effects of the diabetes (D) mutation on utero-ovarian structure and function were examined in match-paired D and control (C) C57BL/KsJ mice between 2 and 16 weeks of age. Between 4 and 8 weeks of age, the uterine epithelium of D mice exhibited a remarkable increase in the amount of cytoplasmic lipid stores as compared with that of C animals. Associated with progressive hyperglycemia between 8 and 16 weeks of age, uterine atrophy and continued lipid accumulation occurred. Both serum progesterone and estradiol levels were lower in D than C mice between 8 and 16 weeks of age. In addition, the uteri of D mice failed to accumulate as much 3H-estradiol as C uteri at 16 weeks of age. These data demonstrate that changes in uterine structure that are attributable to depressed ovarian activity in diabetics underlie the reproductive failure in these animals. The temporal association between the onset of reproductive tract involution and the expressed hyperglycemic condition suggests a causal association between these events in the genetically diabetic C57BL/KsJ mouse.