Dietary advanced glycation end products (AGEs) and superovulation with gonadotropins alter RAGE expression in the ovaries differently at each follicular stage of development

Abstract

The purpose of this study was to examine the deposition of advanced glycation end products (AGEs) and their receptors, RAGE, in ovarian follicles during folliculogenesis in mice fed high (H-AGE) or low (L-AGE) AGE diets and following superovulation with gonadotropins. We hypothesize that H-AGE diet is associated with increased AGE deposition and RAGE expression in various stages of ovarian follicular development, and superovulation with gonadotropins may alter these changes. C57BL/6J mice were fed low L-AGE (n = 10) or H-AGE (n = 10) diet for 12 weeks. In each group, half of each cohort (n = 5) were sacrificed at the end of 12 weeks while the other half (n = 5) were superovulated prior to sacrifice. Immunofluorescence staining of ovarian sections was used to determine AGE deposition and RAGE expression in ovarian follicles in a semi-quantitative manner. In all mice, AGE deposition and RAGE expression were observed in granulosa but not theca cells. In all mice, AGE deposition intensity increased as the follicles progressed through developmental stages from primordial to primary to secondary to prenatral/antral but then significantly dropped in the corpus luteum stage. RAGE staining was highly expressed equally in all stages of pre-ovulatory follicles but then significantly dropped in the corpus luteum post-ovulatory stage. Compared to mice on L-AGE diet, mice on H-AGE mice had significantly lower AGE deposition in their primordial follicles and lower RAGE intensity in their antral follicles. Following superovulation, mice in both groups had significantly lower AGE deposition and significantly lower RAGE expression but the drop in AGE deposition following superovulation was more pronounced in the H-AGE diet group compared to the L-AGE diet group in both pre-ovulatory and post-ovulatory follicles. Ovarian AGE deposition and RAGE expression changes differently during the natural follicular development. Opposite to expectations, the intake of diet rich in AGEs caused lower expression of the proinflammatroy RAGE, an effect that was more pronounced after gonadotropin exposure.