Influence of in utero exposure to ondansetron: possible teratogenic effects and late repercussion on reproductive and behavioral parameters in male rats

Author(s)

Ana Carolina Casali Reis

• Document type: Master's Dissertation
• Press: Botucatu. 2022-06-28.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2022-02-25
• Advisor: Arielle Cristina Arena

Abstract

Ondansetron is a highly selective serotonin 5HT3 receptor antagonist used in the prevention and treatment of nausea and vomiting. It is considered a category B drug, contraindicated for pregnant women without medical or dental surgeon guidance, however, it is widely used to relieve nausea and vomiting during pregnancy. Few data evaluating the use of this drug during pregnancy are available in the literature. Thus, the objective is to evaluate the possible teratogenic effects and late impacts of ondansetron on reproductive and behavioral parameters in male offspring after intrauterine exposure. For this, Wistar rats diagnosed with pregnancy were allocated into three groups (n=20/group), being a control group (distilled water) and two groups treated with different doses of ondansetron (1.7 or 2.5 mg/kg /day, orally). Part of the animals n=10/group was exposed to the drug from the 6th to the 15th day of pregnancy (period corresponding to organogenesis), and the other part was exposed throughout the entire pregnancy period, covering the first peak of testosterone, essential for the process of hypothalamic sexual differentiation. The developed results indicate that ondansetron was not able to significantly alter the hypothalamic sexual differentiation process, with no changes in masculinization and puberty markers, anogenital distance, and preputial separation respectively. Other sperm and fertile parameters evaluated remained unchanged, limiting their impacts on peripubertal life, altering the pattern of social behavior. Assessments of teratogenicity did not indicate that the use of ondansetron during organogenesis increases the risk of external, visceral, or skeletal malformations. However, changes in biochemical and histological parameters of pregnant rats treated from pregnancy day 6 to 15 pointed to kidney injury. (AU)

• FAPESP's process: 20/08745-9 - Influence of in utero exposure to ondansetron: teratogenic effects and late repercussions on reproductive and behavioral parameters in male rats
• Grantee: Ana Carolina Casali Reis
• Support Opportunities: Scholarships in Brazil - Master