Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring

Andretta, Rhayza Roberta; Okada, Fatima Kazue; Paccola, Camila Cicconi; Stumpp, Taiza; Oliva, Samara Urban de; Miraglia, Sandra Maria

doi:10.1016/j.reprotox.2013.09.009

Cited by 11 publications

(9 citation statements)

References 65 publications

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“…Chemicals including drugs can decrease fertility and even lead to infertility in both males and females by disrupting the normal function of this axis [41]. It has been shown that antiepileptic drugs also influence hypothalamic-pituitary-gonadal axis and cause reproductive dysfunction [6, 36–38, 42–44]. In our study, decreased serum FSH, LH, and testosterone levels were observed in our high-dose group.…”

Section: Discussionsupporting

confidence: 54%

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress

et al. 2017

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Levetiracetam (LEV) is an antiepileptic drug commonly used in the treatment of epilepsy because of its excellent safety profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug on the male reproductive system, as it is commonly used in male patients of reproductive age. From this point of view, our aim was to evaluate the possible toxic effects of LEV on the male reproductive system. Therefore, LEV was administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive days. At the end of this period, alterations to body and organ weights were calculated, and sperm concentration, motility, and morphology were investigated by a computer-assisted sperm analysis system. Sperm DNA damage was determined by comet assay and histopathological examination of the testes was carried out. Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured by ELISAs to determine the effects of hormonal status, while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in the testes were measured by colorimetric assay kits to determine the role of oxidative status in potential toxicity. According to the results, sperm quality was decreased by LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in the 150 and 300 mg/kg LEV-administered groups. Histopathology of the testes showed that LEV resulted in testicular injury in the 300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were significantly decreased in the 300 mg/kg LEV-administered group. Glutathione, superoxide dismutase, and catalase levels were significantly decreased in all experimental groups while malondialdehyde levels were significantly increased in 150 and 300 mg/kg LEV-administered groups. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and oxidative stress are potential contributors to reproductive toxicity.

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Section: Discussionsupporting

confidence: 54%

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress

et al. 2017

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“…As presented here, the diabetic rats had a delay in the PS, an androgen‐dependent phenomenon that characterizes pubertal development (Andretta et al . ). Although RES and insulin have improved the testosterone plasma level, neither could normalize the time of PS in the diabetic rats.…”

Section: Discussionmentioning

confidence: 97%

“…The establishment of puberty is orchestrated by intense hormonal regulation, especially of testosterone feedback mechanisms (Korenbrot et al 1977). As presented here, the International Journal of Experimental Pathology, 2017, 98, [312][313][314][315][316][317][318][319][320][321][322][323][324][325][326][327][328] diabetic rats had a delay in the PS, an androgen-dependent phenomenon that characterizes pubertal development (Andretta et al 2014). Although RES and insulin have improved the testosterone plasma level, neither could normalize the time of PS in the diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates reproductive alterations in type 1 diabetes‐induced rats

Simas

Mendes

Paccola

et al. 2017

Int J Experimental Path

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The progression of diabetes mellitus leads to several complications including overproduction of reactive oxygen species and reproductive alterations. As resveratrol (RES) is a powerful anti-oxidant and an anti-apoptotic compound, we hypothesized that side effects of type-1 diabetes (DM1) on male reproduction could be reduced by the RES treatment. Eighty-four prepubertal male rats were distributed into seven groups: sham-control (SC), RES-treated (R), resveratrol-vehicle-treated (RV), diabetic (D), diabetic-insulin-treated (DI), diabetic-RES-treated (DR), diabetic-insulin and RES-treated (DIR). DM1 was induced by a single intraperitoneal streptozotocin (STZ) injection (65 mg/kg) on the 30th day postpartum (dpp). Animals of DR, DIR and R groups received 150 mg/day of RES by gavage for 43 consecutive days (from the 33 to 75 dpp). DI and DIR rats received subcutaneous injections of insulin (1 U/100 g b.w./day) from 5th day after the DM1 induction. The blood glucose level was monitored. At 75 dpp, the euthanasia was performed for morphometric and biometric testicular analyses, spermatic evaluation and hormonal doses. In the D group, the blood glucose level was higher than in the DR, DI and DIR groups. Besides morphometric testicular measurements, testosterone and estradiol doses were lower in D group than in DR and DIR groups; LH dose was also lower than in DR. The preputial separation age was delayed in diabetes-induced groups. The DR and DIR groups showed an improvement in sperm mitochondrial activity, epididymal sperm counts and the frequency of morphologically normal sperms. RES treatment improved glycaemic level, sperm quantitative and qualitative parameters and the hormonal profile in DM1-induced rats and seems to be a good reproductive protector.

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“…However, little is known about the possible late harmful effects of prenatal CBZ exposure and other antiepileptic drugs on the testicular development, sperm parameters and fertility and progeny outcomes. In a previous study, our group showed that exposure to CBZ during gestation and lactation caused, in rats, delayed pubertal development and sperm changes in the progenies, which were observed at late puberty, as well as a possible interference with steroidogenesis (Andretta, Okada, Paccola, Stumpp, Oliva, & Miraglia, 2014). Nevertheless, there are no comparative data regarding the testicular and sperm parameters of the progenies from CBZ‐exposed rat dams at two different stages of pregnancy.…”

Section: Introductionmentioning

confidence: 97%

Maternal CBZ exposure impairs testicular development, spermatogenesis and sperm parameters in male offspring at puberty

2020

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Carbamazepine (CBZ) is widely used in the control of convulsive crisis, treatment of trigeminal neuralgia and affective disorders. This drug has been administered to pregnant women to prevent seizures, and this antiepileptic drug (AED) treatment cannot be discontinued because of the risk of seizures during pregnancy, which can be harmful to both mother and child (Pennell, 2013). CBZ crosses the placental barrier, reaching the embryo/foetus. The use of CBZ during gestation is associated with a twofold or threefold increase in the occurrence of congenital malformations (Matalon, Schechtman, Goldzweig, & Ornoy, 2002). Also, CBZ inhibits testicular steroidogenesis, directly interfering in monooxygenase activities of cytochromes P-450 and affecting androgen-dependent processes (Kühn-Velter, Herzog, &

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Carbamazepine-exposure during gestation and lactation affects pubertal onset and spermatic parameters in male pubertal offspring

Cited by 11 publications

References 65 publications

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress

Resveratrol attenuates reproductive alterations in type 1 diabetes‐induced rats

Maternal CBZ exposure impairs testicular development, spermatogenesis and sperm parameters in male offspring at puberty

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