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Treatment with topiramate in rats during childhood causes testicular structural impairment at adulthood

Published online by Cambridge University Press:  03 November 2022

Lorena Ireno Borges ,
Simone Forcato ,
Lays Cristine do Nascimento Olanda ,
Giovanna Fachetti Frigoli ,
Camila Borecki Vidigal ,
Kawane Fabrício Moura ,
Glaura Scantamburlo A. Fernandes Open the ORCID record for Glaura Scantamburlo A. Fernandes [Opens in a new window] ,
Maria do Carmo Pinho Franco Open the ORCID record for Maria do Carmo Pinho Franco [Opens in a new window] ,
Graziela Scalianti Ceravolo Open the ORCID record for Graziela Scalianti Ceravolo [Opens in a new window]  and
Daniela Cristina Ceccatto Gerardin Open the ORCID record for Daniela Cristina Ceccatto Gerardin [Opens in a new window]
Lorena Ireno Borges
Affiliation:
Department of Physiological Sciences, State University of Londrina, Londrina, Paraná, Brazil
Simone Forcato
Affiliation:
Department of Physiological Sciences, State University of Londrina, Londrina, Paraná, Brazil
Lays Cristine do Nascimento Olanda
Affiliation:
Department of Physiological Sciences, State University of Londrina, Londrina, Paraná, Brazil
Giovanna Fachetti Frigoli
Affiliation:
Department of Biology, State University of Londrina, Londrina, Paraná, Brazil
Camila Borecki Vidigal
Affiliation:
Department of Physiological Sciences, State University of Londrina, Londrina, Paraná, Brazil
Kawane Fabrício Moura
Affiliation:
Department of Physiological Sciences, State University of Londrina, Londrina, Paraná, Brazil
Glaura Scantamburlo A. Fernandes
Affiliation:
Department of Biology, State University of Londrina, Londrina, Paraná, Brazil
Maria do Carmo Pinho Franco
Affiliation:
Division of Nephrology, School of Medicine, Federal University of São Paulo, São Paulo, Brazil
Graziela Scalianti Ceravolo
Affiliation:
Department of Physiological Sciences, State University of Londrina, Londrina, Paraná, Brazil
Daniela Cristina Ceccatto Gerardin*
Affiliation:
Department of Physiological Sciences, State University of Londrina, Londrina, Paraná, Brazil
*
Address for correspondence: Daniela Cristina Ceccatto Gerardin, Department of Physiological Sciences, State University of Londrina- UEL, 86051-980 Londrina, Paraná, Brazil. Email: dcgerardin@uel.br
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Abstract

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.

Keywords

Developmentpubertyreproductionspermatozoatestis
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 14 , Issue 2 , April 2023 , pp. 279 - 285
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Copyright
© The Author(s), 2022. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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