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Reduced Ovarian Glyoxalase-I Activity by Dietary Glycotoxins and Androgen Excess: A Causative Link to Polycystic Ovarian Syndrome. Kandaraki E et al. Glyoxalase detoxification system composed of glyoxalase-I and II (GLO-I, II), is ubiquitously expressed and implicated in the protection against cellular damage due to cytotoxic metabolites such as advanced glycation end-products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGEs deposition been associated either with a high AGEs diet in experimental animals or hyperandrogenic disorders like Polycystic Ovarian Syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal non-androgenized (NAN, Group A, n=18) and androgenised prepubertal (AN) rats (Group B, n=29). Both groups were further randomly assigned, either to high (HA) or low (LA) AGE content diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed with HA diet compared to LA (p=0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared to NAN (p=0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (r(s)=0.533, p<0.001), estradiol (r(s)=0.326, p=0.033) and progesterone levels (r(s)=0.500, p<0.001). A negative correlation was observed between GLO-I activity and AGEs expression in the ovarian granulosa cell layer of all groups with marginal statistical significance (r(s)=-0.263, p=0.07). The present data demonstrate that ovarian GLO-I activity may be regulated by dietary composition and androgen levels. Modification of ovarian GLO-I activity observed for the first time in this androgenised prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterising PCOS.
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