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

IF 1.8 4区医学 Q3 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Journal of Developmental Origins of Health and Disease Pub Date : 2023-04-01 DOI:10.1017/S2040174422000587

Lorena Ireno Borges, Simone Forcato, Lays Cristine do Nascimento Olanda, Giovanna Fachetti Frigoli, Camila Borecki Vidigal, Kawane Fabrício Moura, Glaura Scantamburlo A Fernandes, Maria do Carmo Pinho Franco, Graziela Scalianti Ceravolo, Daniela Cristina Ceccatto Gerardin

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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.

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在儿童期用托吡酯治疗大鼠可导致成年期睾丸结构损伤。

托吡酯(TOP)是一种精神药物，用于治疗2岁以上儿童癫痫和预防青少年偏头痛。有证据表明，TOP会对雄性大鼠的生殖系统产生负面影响。本研究旨在评价TOP在儿童期和青春期对雄性大鼠生殖系统的即时和后期治疗效果。两个实验组从出生后第16天至第28天(TOPc组)或第28天至第50天(TOPa组)每天灌胃给予41 mg/kg TOPa。对照组(CTRc组和CTRa组)每天饮水。一半的动物在治疗结束后24小时进行评估(分别为PND 29和PND 51)，其余动物在成年期进行评估(PND120)。测定以下参数:肛门生殖器距离、精子评价、睾丸组织形态测定和血浆睾酮浓度。PND 120时，体积(CTRc:62.58±2.13;TOPc: 54.54±2.10*%，p = 0.018)，总长度(CTRc: 25.48±1.61;精小管TOPc: 18.94±2.41*，p = 0.035)减少，间质组织体积(CTRc:37.41±2.13;TOPc: 45.45±2.09*%，p = 0.018)，睾丸间质细胞/睾丸数(CTRc: 277.00±36.70;TOPc组TOPc: 400.20±13.23*，p = 0.013)升高。其他参数在两组之间保持相似。因此，本研究有助于我们理解儿童期TOP治疗对成年期大鼠生殖系统的影响，表明这一时期对TOP暴露比青春期更敏感。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Developmental Origins of Health and Disease PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH-

CiteScore

3.80

自引率

0.00%

发文量

145

审稿时长

6-12 weeks

期刊介绍： JDOHaD publishes leading research in the field of Developmental Origins of Health and Disease (DOHaD). The Journal focuses on the environment during early pre-natal and post-natal animal and human development, interactions between environmental and genetic factors, including environmental toxicants, and their influence on health and disease risk throughout the lifespan. JDOHaD publishes work on developmental programming, fetal and neonatal biology and physiology, early life nutrition, especially during the first 1,000 days of life, human ecology and evolution and Gene-Environment Interactions. JDOHaD also accepts manuscripts that address the social determinants or education of health and disease risk as they relate to the early life period, as well as the economic and health care costs of a poor start to life. Accordingly, JDOHaD is multi-disciplinary, with contributions from basic scientists working in the fields of physiology, biochemistry and nutrition, endocrinology and metabolism, developmental biology, molecular biology/ epigenetics, human biology/ anthropology, and evolutionary developmental biology. Moreover clinicians, nutritionists, epidemiologists, social scientists, economists, public health specialists and policy makers are very welcome to submit manuscripts. The journal includes original research articles, short communications and reviews, and has regular themed issues, with guest editors; it is also a platform for conference/workshop reports, and for opinion, comment and interaction.