Insight into the mechanism of aspartame‐induced toxicity in male reproductive system following long‐term consumption in mice model

Abstract

Aspartame is one of the most common consumed artificial sweeteners utilized in many food products and beverages. It has been indicated that long‐term consumption of aspartame leads to reproductive toxicity but its mechanism is not well‐clear. In this study we investigated mechanism of aspartame‐induced reproductive toxicity in male mice. For this purpose, 36 NMRI mature male mice received three doses of 40, 80, and 160 mg/kg body weight of aspartame, respectively per day by gavage for 90 days and also a control group was considered which received 0.5 mL of normal saline as the same route. The results revealed that long‐term administration of aspartame at high doses significantly (P < .05) reduced gonadosomatic index, serum concentration of pituitary‐testicular axis hormones (FSH, LH, and testosterone). It also decreased sperm parameters and total antioxidant capacity, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), while it caused increase in nitric oxide and malondialdehyde levels in testis tissue and sperm samples. Also, it decreased attenuated testicular histomorphometric indices (tubular differentiation index, spermiogenesis index, and repopulation index), and steroidogenic foci, while increased mRNA damages and apoptosis rate, downregulated antiapoptotic (Bcl‐2) and upregulated proapoptotic (P53, BAX, and caspase‐3) mediators respectively in testis. These findings indicated that consumption of aspartame for a long period results in male reproductive toxicity by decrease in serum concentration of pituitary‐testis axis hormones and induction of oxidative stress and apoptosis in testis.

Evaluation of Some Male and Female Rats’ Reproductive Hormones Following Administration of Aspartame With or Without Vitamin C or E

“…Similarly, long-term ASP treatment is shown to enhance lipid peroxidation and nitric oxide levels, resulting in the generation of free radicals that disrupt homeostasis. In mice and rats (10), ASP inhibits the production of reproductive hormones by lowering the levels of LH, FSH, and testosterone (11). Vitamins C and E, on the other hand, are antioxidants that may decrease the consequences of oxidative stress-related testicular dysfunction in animal tissues.…”

Consumption of Sugar-Sweetened or Artificially Sweetened Beverages and Semen Quality in Young Men: A Cross-Sectional Study

“…We cannot exclude that the changes found for morphology might be a chance finding. Gong et al and Anbara et al found evidence of associations between intake of saccharin and aspartame on testis function in mice, but no particular effect on morphology was found [ 38 , 39 , 40 ].…”

“…This might increase the risk of obesity and metabolic syndrome, due to higher intake of sugary foods and drinks, and potentially impact male reproduction, including semen quality. In addition, mice studies have found that exposure to high levels of artificial sweeteners, such as saccharin and aspartame, affects several sperm and testicular parameters negatively and, furthermore, interfered with hormones of the hypothalamic-pituitary-gonadal axis [ 38 , 39 , 40 ].…”

Repro‐protective role of royal jelly in phenylhydrazine‐induced hemolytic anemia in male mice: Histopathological, embryological, and biochemical evidence

“…The percentages of seminiferous tubules with positive TDI, SPI and RI were determined in five semi-serial sections from each sample. 20…”

“…The damage of RNA was analyzed as previously described. 20 The testicular germ cells with damaged RNA were determined through RNA loss and/or faint red-colored RNA content. The intact cells were characterized via bright red RNA at nucleolus apex.…”