Topiramate treatment during adolescence induces short and long-term alterations in the reproductive system of female rats

• Published in: Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2024-06, Vol.126, p.108601, Article 108601
• Main Authors: Bilibio, Júlia Oliveira, Forcato, Simone, da Silva, Deborah Gomes, Borges, Lorena Ireno, Frigoli, Giovanna Fachetti, Franco, Maria do Carmo Pinho, Fernandes, Glaura Scantamburlo Alves, Ceravolo, Graziela Scalianti, Gerardin, Daniela Cristina Ceccatto
• Format: Article
• Language: English
• Subjects: Adolescence; Animals; Anticonvulsants - toxicity; Antiepileptic drug; Developmental plasticity; Endocrine disruptor; Female; Fructose - analogs & derivatives; Fructose - toxicity; HPG axis; Organ Size - drug effects; Ovary - drug effects; Rats; Rats, Wistar; Topiramate - toxicity; Uterus - drug effects
• ISSN: 0890-6238; 1873-1708; 1873-1708
• DOI: 10.1016/j.reprotox.2024.108601

Topiramate (TPM) is an antiepileptic drug used for treating epilepsy in children, and migraine in teenagers. In this context, preclinical studies with adult female rats observed reproductive system abnormalities following treatment with TPM. Additionally, exposure to endocrine disruptors during developmental plasticity periods, such as childhood and adolescence, may influence characteristics in the adult individual. This study evaluated whether treatment with TPM during developmental periods influences the reproductive system of female rats either immediately or in adult life. Female Wistar rats were treated with TPM (41 mg/Kg/day) by oral gavage from postnatal day (PND) 16–28, or PND 28–50, which correspond to childhood and adolescence, respectively, and euthanized either 24 h after the final administration or during adulthood. Treatment with TPM during adolescence induced short-term increase in uterus and ovary weights and reduction in endometrial stroma thickness. Adult animals treated during adolescence displayed reduced primordial ovarian follicles’ numbers, and increased primary and pre-antral ovarian follicles’ numbers. Treatment during childhood induced no short or long-term differences. These results indicate TPM treatment during adolescence is capable of inducing short and long-term alterations on the reproductive system of female Wistar rats. •TPM treatment in adolescence acutely reduced endometrial stroma thickness.•Treatment in adolescence increased reproductive organ weights of adolescent rats.•TPM reduced primordial follicles’ number in adult rats treated in adolescence.•Adolescence-treated adults had increased primary and pre-antral follicles’ numbers.•TPM treatment during childhood caused no short or long-term reproductive changes in female rats.