The Effect of Long-term Exposure to Aspartame on Histomorphometric, Histochemical and Expression of P53, Bcl-2 and Caspase-3 Genes in the Ovaries of Mice

Background and Objectives: Aspartame is a non-nutritive and artificial sweetener which is widely used in diet and low calorie products and also in a variety of foods, drugs and hygiene products. The present study has been conducted in order to evaluation of the effects of aspartame on ovaries in female mice. Methods: In this experimental study, 36 adult female mice were randomly divided into four groups of nine each. For three groups aspartame was administered orally with the doses of 40, 80 and 160 mg/kg.BW respectively, and one group as the control group received normal saline for 91 days by gavage. Also a control group was considered. 24 hours after the last treatment, ovarian tissue and blood samples were collected and used for biochemical, histomorphological, histomorphometric, histochemical and gene expression studies. The obtained data were analyzed using One-Way Analysis of Variance (ANOVA) and Tukey’s test at the significance level of P<0.05. Results: In ovarian histomorphometric studies, aspartame at a dose of 160 mg/kg significantly reduced growing follicles and significantly increased atresia follicles. Also in biochemical studies caused a significant decrease in TAC and a significant increase in MDA compared to control group. In connection with the studied genes, aspartame at a dose of 160 mg/kg caused a significant decrease in the expression of Bcl-2 gene and also a significant increase in the expression of P53 and Caspase-3 genes compared to the control group. Conclusion: It seems that high dose aspartame can cause adverse effects on histomorphology, histomorphometry and expression of P53, Bcl-2 and Caspase-3 genes in rat ovaries