Faster rates of post-puberty kidney deterioration in males is correlated with elevated oxidative stress in males vs females at early puberty

The number of genes exhibiting gender-dependent expression was highly influenced by the genetic background of the rat group examined. 373, 288 and 79 genes showed differential gene expression between males and females (p = 0.001) in US, Mhm and Mhm*BN rats, respectively. Of all gender dependently expressed genes, only 39 genes were differentially expressed in all tested groups and the direction of expression change was the same for those genes for all groups. The gene expression profile suggests higher metabolic and transport activities, enhanced cell proliferation, elevated oxidative stress, and altered vascular biology in males. Furthermore, elevated levels of superoxide anion (two- to three-fold) in males compared to females were detected at early puberty, but neither at pre-puberty nor at late puberty/early adulthood.Our data suggest that early puberty, with gender-related elevation in oxidative stress in males, is a key compromising factor on kidneys in males.Post-puberty deterioration and aging of kidneys seem to occur more rapidly in males than in females, characterized by shorter telomeres in males [1,2]. It is also well documented that many kidney diseases, such as hypertensive and diabetic renal diseases, glomerulonephritis, and polycystic kidney disease (PKD), have an earlier onset, higher prevalence and more rapid progression in males compared with females in human, mouse and rat [3-6].Existing data support strong influences of sex hormones on renal function [6-8]. Gender differences in kidney function emerge at puberty, when sex hormones appear, and diminish later in life when females enter menopause. This difference can be greatly reduced or eliminated by orchiectomy, ovariectomy or hormone blockage [5,6]. Estrogen has been reported to protect against kidney deterioration, probably via its anti-oxidative and anti-inflammatory effects [7]. Androgens, on the other hand, have been shown to enhance fibrogenesis [9]. The exact mechanisms by which sexual hor