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

Abstract

The symptoms of nausea and vomiting during pregnancy (NVP) are a clinically significant condition, capable of affecting more than 80% of pregnant women, interfering with the quality of life, and can lead to psychosocial impacts. Ondansetron, a highly selective 5HT-3 serotonin receptor antagonist, is used in the prevention and treatment of nausea and vomiting in general, induced by chemotherapy, radiotherapy, and postoperative. Although ondansetron is considered a Category B drug, contraindicated for pregnant women without guidance it is widely used to relieve NVP. Few studies evaluating the use of this medication during pregnancy are available in the literature. Studies report that 5HT-3 receptors, the target of this drug, may be involved in the processes of inhibition or stimulation of the release of neurotransmitters, causing changes in the pattern, and interfering with brain development, which may cause functional and structural consequences in the process of hypothalamic sexual differentiation. Since the period of high intensity of symptoms (first trimester of pregnancy) corresponds to organogenesis, this research attempts to elucidate the possible teratogenic character, and evaluate the late impacts of ondansetron on reproductive and behavioral parameters in male offspring after intrauterine exposure. For this, pregnant Wistar rats will be allocated into three groups (n=20/group), one control group (distilled water) and two groups treated with ondansetron (1.7 or 2.5 mg/kg/day, by gavage). Half of the animals (n = 10/group) will be exposed to the medication from the 6th to the 15th gestational day (organogenesis period), and the other half will be exposed throughout the gestational period, covering the first testosterone peak, essential for the hypothalamic sexual differentiation process. (AU)