Fetal programming by sodium saccharin and damage on male offspring reproductive

Male infertility is responsible for 20-70% of infertility in couples. We investigated the effects of fetal programming with sodium saccharin consumption in testis structure and function and in male offspring fertility. Feed intake and efficiency, organ and fat weight, quantification and expression of AR and PCNA proteins, sperm count and hormonal dosages were performed. Changes in consumption were found in the final weeks of the experiment. Decreases in the expression and quantification of AR and PCNA, tubular diameter and luminal volume, and increase in epithelial and interstitial relative volumes were observed. Lower sperm count and transit and lower estradiol concentration were also found. The consumption of sodium saccharin by the dams programmed the male offspring affecting the HPG axis with alterations in Sertoli cell proliferation, AR expression and quantification, and sperm count. We hypothesize that these changes may be due to the reduction of estradiol that caused the loosening of the tight junctions of the blood-testis-barrier (BTB), causing cell losses during spermatogenesis, also reflecting, under the decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. Sodium saccharin programming directly affected the reproductive parameters of male offspring and adult fertility.

Effects of Saccharin Consumption on Operant Responding for Sugar Reward and Incubation of Sugar Craving in Rats

Repeated experience with artificial sweeteners increases food consumption and body weight gain in rats. Saccharin consumption may reduce the conditioned satiety response to sweet-tasting food. Rats were trained to press a lever to obtain sucrose for five days. A compound cue (tone + light) was presented with every sucrose delivery. On the following day, each lever press produced only the compound cue (cue-reactivity test). Subjects were then provided with yogurt for three weeks in their home cages. The rats were divided into two groups. Rats in the saccharin group received yogurt sweetened with saccharin on some days and unsweetened yogurt on others. For the plain group, only unsweetened plain yogurt was provided. Subsequently, the cue-reactivity test was conducted again. On the following day, the rats underwent a consumption test in which each lever press was reinforced with sucrose. Chow consumption and body weight gain were larger in the saccharin group than in the plain group. Lever responses increased from the first to the second cue-reactivity tests (incubation of craving) in both groups. During the consumption test, lever responses were higher in the saccharin group than in the plain group, suggesting that the conditioned satiety response was impaired in the saccharin group.

Social interaction with an alcohol-intoxicated or cocaine-injected peer selectively alters social behaviors and drinking in adolescent male and female rats

BackgroundDrinking alcohol is facilitated by social interactions with peers, especially during adolescence. The importance of peer social influences during adolescence on alcohol and substance use have recently received more attention. We have shown that social interaction with an alcohol-intoxicated peer influences adolescent alcohol drinking differently in male and female rats using the demonstrator-observer paradigm. The present set of experiments analyzed the social interaction session to determine behaviors that influence alcohol drinking in adolescent male and female rats.MethodsSpecifically, in experiment one we determined which behaviors were altered during social interaction with an alcohol-intoxicated demonstrator and assessed changes in ethanol intake in adolescent observers. Experiment two examined changes in voluntary saccharin consumption to determine if social interaction with an alcohol-intoxicated demonstrator altered consumption of a palatable solution. In experiment three, we administered a low (5 mg/kg) or high (20 mg/kg) dose of cocaine to the demonstrator and assessed changes in the adolescent observers to determine if social interaction with a ‘drugged’ peer altered social behaviors and voluntary ethanol intake.ResultsWe showed that social interaction with an alcohol-intoxicated demonstrator (1) decreased social play and increased social investigation and social contact in adolescent male and female observers, (2) did not alter non-social behaviors, (3) did not alter saccharin consumption and (4) increased voluntary ethanol intake in adolescent female but not male observers. When the peer was injected with cocaine (1) social play was dose-dependently decreased, (2) there were no changes in other social or non-social behaviors, and (3) voluntary ethanol intake in adolescent male and female observers was unaffected.ConclusionsThe present results are consistent and extend our previous work showing that social interaction with an alcohol-intoxicated peer selectively alters social behaviors and alcohol-drinking in adolescent rats. Females appear to be more sensitive to elevating effects of social interaction on voluntary ethanol consumption.

A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity

ABSTRACT Background Low-calorie sweeteners (LCSs) provide sweetness with little or no energy. However, each LCS's unique chemical structure has potential to elicit different sensory, physiological, and behavioral responses that affect body weight. Objective The purpose of this trial was to compare the effects of consumption of 4 LCSs and sucrose on body weight, ingestive behaviors, and glucose tolerance over a 12-wk intervention in adults (18–60 y old) with overweight or obesity (body mass index 25–40 kg/m2). Methods In a parallel-arm design, 154 participants were randomly assigned to consume 1.25–1.75 L of beverage sweetened with sucrose (n = 39), aspartame (n = 30), saccharin (n = 29), sucralose (n = 28), or rebaudioside A (rebA) (n = 28) daily for 12 wk. The beverages contained 400–560 kcal/d (sucrose treatments) or <5 kcal/d (LCS treatments). Anthropometric indexes, energy intake, energy expenditure, appetite, and glucose tolerance were measured at baseline. Body weight was measured every 2 wk with energy intake, expenditure, and appetite assessed every 4 wk. Twenty-four-hour urine collections were completed every 4 wk to determine study compliance via para-aminobenzoic acid excretion. Results Of the participants enrolled in the trial, 123 completed the 12-wk intervention. Sucrose and saccharin consumption led to increased body weight across the 12-wk intervention (Δweight = +1.85 ± 0.36 kg and +1.18 ± 0.36 kg, respectively; P ≤ 0.02) and did not differ from each other. There was no significant change in body weight with consumption of the other LCS treatments compared with baseline, but change in body weight for sucralose was negative and significantly lower compared with all other LCSs at week 12 (weight difference ≥ 1.37 ± 0.52 kg, P ≤ 0.008). Energy intake decreased with sucralose consumption (P = 0.02) and ingestive frequency was lower for sucralose than for saccharin (P = 0.045). Glucose tolerance was not significantly affected by any of the sweetener treatments. Conclusions Sucrose and saccharin consumption significantly increase body weight compared with aspartame, rebA, and sucralose, whereas weight change was directionally negative and lower for sucralose compared with saccharin, aspartame, and rebA consumption. LCSs should be categorized as distinct entities because of their differing effects on body weight. This trial was registered at clinicaltrials.gov as NCT02928653.