Comparison of diabetic nephropathy between male and female eNOS^-/- db/db mice

—Sex is an important biological variable that impacts diverse physiological and pathological processes, including the progression of diabetic nephropathy. Diabetic nephropathy is one of the most common complications of diabetes mellitus and is the leading cause of end-stage renal disease. The endothelial nitric oxide synthase-deficient (eNOS^+/+) db/db mouse is an appropriate and valuable model to study mechanisms in the development of diabetic nephropathy because of the similarities of the features of diabetic kidney disease in this model to those in humans. The aim of the present study was to determine whether there was a sex difference in renal injury in eNOS^+/+ db/db mice. Both male and female eNOS^+/+ db/db mice showed hyperglycemia, obesity, and renal hypertrophy. However, there was no significant difference in those variables between male and female mice. Furthermore, both male and female diabetic mice showed progressive albuminuria and significantly greater levels of serum creatinine and blood urea nitrogen compared with the same sex of wild-type mice (nondiabetic controls). Although all three variables in female eNOS^+/+ db/db mice had a tendency to be greater than those in male eNOS^+/+ db/db mice, those sex differences were not statistically significant. Moreover, both male and female eNOS^+/+ db/db mice showed significant mesangial expansion, higher glomerular injury scores, profound renal fibrosis, and substantial accumulation of fibronectin and collagen type IV proteins. However, sex differences in those structural changes were not observed. Similarly, survival rates of male and female eNOS^+/+ db/db mice were comparable. Taken together, the results from the present study suggest no sex difference in renal structural and functional damage in eNOS^+/+ db/db mice.