THE OVARIAN ADAPTIVE RESPONSE AGAINST DIETARY-INDUCED DICARBONYL STRESS: INSIGHTS FROM THE MOUSE MODEL

Dicarbonyl stress is a condition characterized by increased levels of highly reactive dicarbonyl compounds, such as methylglyoxal (MG), which interact with biomolecules leading to formation of advanced glycation end products (AGEs). MG and AGEs are known to increase during aging and under conditions of impaired glucose metabolism and/or oxidative stress (OS). In addition, exogenous factors, such as tobacco smoking and diet, may also contribute to increase MG and AGE levels. In the ovary, dicar- bonyl stress occurs during reproductive aging and polycystic ovarian syndrome (PCOS). Based on previous studies on in vitro systems,1 in this work we investigated the ovarian toxicity of dietary MG. Four-week-aged female CD1 mice received water (n=9) or 100 mg/kg MG (n=9) by gastric administration for 28 days.2 Analysis of follicle population revealed no differences in the number of ovarian follicles, although a reduction of PCNA levels suggested negative effects of MG on ovarian stroma. Moreover, MG increased SIRT1 ovarian levels along with over- expression of catalase, superoxide dismutase 2, SIRT3, and PGC1a. Finally, similar levels of ovarian MG-AGEs were observed in the two groups, along with enhanced protein expres- sion of glyoxalase 1, the main MG detoxifying enzyme, in MG mice. Although control and MG mice showed similar ovulation rate, immunofluorescence analysis revealed that oocytes ovulated by MG mice exhibited abnormal meiotic spindles, a condition predisposing to embryo aneuploidy. Taken together our results suggest that MG intake triggers an ovarian adaptive response involving a SIRT1 signalling and anti-glycation defence which prevents MG-AGE accumulation, but negatively affects the development of competent oocytes.