Can exposure to lisdexamfetamine dimesylate from juvenile period to peripubertal compromise male reproductive parameters in adult rats?

Lisdexamfetamine (LDX) is a d-amphetamine prodrug used to treat attention deficit and hyperactivity disorder, a common neurodevelopmental disorder in children and adolescents. Due to its action mediated by elevated levels of catecholamines, mainly dopamine and noradrenaline, which influence hormonal regulation and directly affect the gonads, this drug may potentially disrupt reproductive performance. This study evaluated the effects of exposure to LDX from the juvenile to peripubertal period (critical stages of development) on systemic and reproductive toxicity parameters in male rats. Male Wistar rats (23 days old) were treated with 0; 5.2; 8.6 or 12.1 mg/kg/day of LDX from post-natal day (PND) 23 to 53, by gavage. LDX treatment led to reduced daily food and water consumption, as well as a decrease in social behaviors. The day of preputial separation remained unaltered, although the treated animals exhibited reduced weight. At PND 54, the treated animals presented signs of systemic toxicity, evidenced by a reduction in body weight gain, increase in the relative weight of the liver, spleen, and seminal gland, reduction in erythrocyte and leukocyte counts, reduced total protein levels, and disruptions in oxidative parameters. In adulthood, there was an increase in immobile sperm, reduced sperm count, morphometric changes in the testis, and altered oxidative parameters, without compromising male sexual behavior and fertility. These findings showed that LDX-treatment during the juvenile and peripubertal periods induced immediate systemic toxicity and adversely influenced reproductive function in adult life, indicating that caution is necessary when prescribing this drug during the peripubertal phase.

Maternal exposure of rats to sodium saccharin during gestation and lactation on male offspring†.

We investigated the effects of fetal programming in Sprague-Dawley rats through the maternal consumption of sodium saccharin on the testicular structure and function in male offspring. Feed intake and efficiency, organ and fat weight, quantification and expression of androgen receptor (AR), and proliferating cell nuclear antigen (PCNA) proteins, sperm count, and hormone levels were determined. Consumption alterations were found in the final weeks of the experiment. Decreases in AR and PCNA expression and quantification, tubular diameter, and luminal volume, and increases in epithelial and interstitial relative volumes were observed. Lower sperm count and transit, and lower estradiol concentration were also found. Sodium saccharin consumption by dams programmed male offspring by affecting the hypothalamic-pituitary-gonad axis with alterations in the Sertoli cell population, in spermatogonia proliferation, the expression and quantification of AR, and in sperm count. We hypothesized that these changes may be due to an estradiol reduction that caused the loosening of adhesion junctions of the blood-testis barrier, causing cell losses during spermatogenesis, also reflected by a decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. We conclude that maternal sodium saccharin consumption during pregnancy and lactation programmed alterations in the reproductive parameters of male offspring, thus influencing spermatogenesis.

Parents ethanol use impairs ethanol-naive offspring development and reproduction.

Parental ethanol consumption can influence the offspring phenotype. In this way, we analyzed the impairments of maternal and paternal high ethanol consumption during postpuberty on the physical development, feeding pattern, puberty onset and reproductive function of ethanol-naive offspring to birth to adulthood. Female and male UChB rats (voluntary 10%, v/v ethanol consumer) were divided into a control group (C) and an ethanol exposed group (E) from 65 to 80 days of age. The C and E were mated at 100 days. The maternal parameters and offspring development and reproduction parameters were monitored. We observed reduced feeding intake and body weight in the dams of E group throughout gestation and lactation period. Delay in physical development, lower body weight and altered feeding pattern were observed in female and male offspring of E group. In addition, the puberty onset was delayed in both sexes, with lower testosterone levels in the juvenile and pubertal males. There was a prolongation on the estrous and proestrus phases in females from E but the estrous cycle duration did not change between groups. Ovary and uterus weight were reduced in pubertal and adult females from E group. Reduced epididymis and seminal vesicle weight, increased sperm abnormalities, decrease in the daily sperm production and accelerated epididymal transit time were observed in E males. The high maternal and paternal ethanol use on postpuberty impairs the parameters of ethanol-naive offspring inducing alteration on development and reproduction.