Effects of Daily Exposure to Saccharin and Sucrose on Testicular Biologic Functions in Mice

Abstract

Saccharin sodium consumption is considered safe and beneficial, owing to its very intense sweetness without any associated calories, but supporting scientific data remain sparse and controversial. Herein, we demonstrate that dose-response relationships existed with regard to administration of saccharin or sucrose to mice for 35 days, and this association involved testis-expressed sweet-tasting molecules (taste receptor type 1 subunit 3 [T1R3]; G protein alpha-gustducin [Galpha]). Mouse body weights and testis weights in middle- and low-dose saccharin-treated groups were increased with up-expressions of molecules involved in testicular sweet taste and steroidogenic (middle saccharin: steroidogenic acute regulatory protein [StAR]; P450 cholesterol side-chain cleavage enzyme [CYP11A1]; 17-alpha-hydroxylase/C17,20-lyase [CYP17A1]; low saccharin: StAR). Moreover, a high-dose saccharin-related decline in reproductive hormone levels and injuries to testis and sperm were observed to be associated with suppression of testicular T1R3 and Galpha, as well as steroidogenic-related factors (StAR; 3-beta-hydroxysteroid dehydrogenase [3-beta-HSD]; CYP11A1; CYP17A1; 17-beta-hydroxysteroid dehydrogenase [17-beta-HSD]), and activation of cleaved caspase-3. However, abnormalities of the testis and sperm in high- and middle-dose sucrose-exposed mice were related to the increased-cleaved caspase-3, but independent of T1R3 and/or Galpha. Collectively, our results clearly suggest that saccharin-induced physiologic effects on testis are associated with testicular T1R3 and Galpha, which differed from sucrose. We hence call for a reassessment of the excessive use of sweeteners in daily life, especially artificial ones, considering their potential side effects.

Effects of dietary sweeteners supplementation on growth performance, serum biochemicals, and jejunal physiological functions of broiler chickens

“…Several previous studies have reported that SAC is capable of binding the bitter taste receptors at high concentration ( Behrens et al., 2017 , Kuhn et al., 2004 ). A previous study has also shown that high-dose SAC treatment could damage testicular functions via activating testicular bitter taste receptors, whereas low-dose and middle-dose SAC treatments could not activate the bitter taste receptors and have no adverse effects on the testicular functions in mice ( Gong et al., 2016 ). Therefore, in the present study, there is a possibility that the activation of jejunal bitter taste receptors was because of the high supplemented level of SAC in the feed.…”

Lactobacillus rhamnosus PB01 (DSM 14870) supplementation affects markers of sperm kinematic parameters in a diet-induced obesity mice model

“…The higher testicular weight observed in the DIO compared to the NW groups could be due to the higher sucrose levels provided in the high fat diet [ 46 ]. Additionally, the significantly higher testicular weight in probiotic supplemented DIO mice in comparison to their age- and diet-matched controls with no probiotic supplementation, could be related to the higher levels of circulating testosterone and prevention of diet-related testicular atrophy by the probiotic supplementation as suggested by previous studies [ 30 ].…”

Influences of non‐nutritive sweeteners on ovarian and uterine expression of T1R2 and T1R3 in peripubertal female guinea pigs

“…Furthermore, a high-dose saccharin-related decline in reproductive hormone levels and injuries to testis and sperm was observed to be associated with suppression of testicular T1R3 in a previous study in male rats (Gong, Wei, Mao, Nagaoka, et al, 2016b). Therefore, the TA B L E 3 Relative levels of immunostaining of sweet taste receptors in guinea pig uteri mechanism behind the reproduction function of T1R2 and T1R3 in reproductive organs requires further investigation.…”