Topiramate (TOP) is a psychotropic drug prescribed for the treatment of epilepsy in children older than 2 years of age and for migraine prophylaxis in adolescents. There is evidence that TOP promotes negative effects on the reproductive system of male rats. This study aimed to evaluate the immediate and late treatment effects of TOP during childhood and adolescence on the male rat reproductive system. Two experimental groups received 41 mg/kg of TOP daily, by gavage, from postnatal day (PND) 16 to 28 (TOPc group) or from PND 28 to 50 (TOPa group). Control groups (CTRc group or CTRa group) received water daily. Half of the anim–als were evaluated 24 h after the end of treatment (PND 29 and PND 51, respectively) and the remainder were evaluated in adulthood (PND120). The following parameters were determined: anogenital distance, sperm evaluation, testis’ histomorphometry and plasma testosterone concentration. At PND 120, the volume (CTRc:62.58 ± 2.13; TOPc: 54.54 ± 2.10*%, p = 0.018) and total length (CTRc: 25.48 ± 1.61; TOPc: 18.94 ± 2.41*, p = 0.035) of seminiferous tubules were decreased and the volume of interstitial tissue (CTRc:37.41 ± 2.13; TOPc: 45.45 ± 2.09*%, p = 0.018) and number of Leydig cells/testis (CTRc: 277.00 ± 36.70; TOPc: 400.20 ± 13.23*, p = 0.013) were increased in the TOPc group. The other parameters remained similar between the groups. Therefore, the present study contributes to our understanding that childhood treatment with TOP has an impact on the rat reproductive system in adulthood, suggesting that this period is more sensitive to TOP exposure than adolescence.

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Malathion is an insecticide that is used to control arboviruses and agricultural pests. Adolescents that are exposed to this insecticide are the most vulnerable as they are in the critical period of postnatal sexual development. This study aimed to evaluate whether malathion damage can affect sperm function and its respective mechanisms when adolescents are exposed during postnatal sexual development. Twenty-four male Wistar rats (PND 25) were divided into three experimental groups and treated daily for 40 d: control group (saline 0.9%), 10 mg/kg (M10 group), or 50 mg/kg (M50 group) of malathion. At PND 65, the rats were anesthetized and euthanized. Testicles were collected for the evaluation of gene expression. Sperm cells from the epididymis were used for evaluation of the oxidative profile or spermatic function. Data showed that a lower dose of malathion downregulated the gene expression of androgen receptors and testosterone converter enzyme 17-β-HSD in the testis. The acrosomal integrity of sperm cells was compromised in the M50 group, but not the M10 group. The mitochondrial activity was not impaired by exposure. Finally, although no alterations in malondialdehyde and glutathione levels were observed, malathion, at both doses, increased antioxidant enzyme catalase activity and, at a higher dose, superoxide dismutase activity. The present study showed that low doses of malathion considered to be inoffensive are capable of impairing sperm quality and function through the downregulation of testicular genic expression of AR enzyme 17-β-HSD and can damage the spermatic antioxidant profile during critical periods of development.