Prenatal exposure to sertraline, associated or not with stress, can negatively program somatic and neurobehavioral development of female rats, and dysregulate reproductive function in adulthood.

Selective serotonin reuptake inhibitors (SSRIs) are prescribed to pregnant women for treating mental illnesses. Among the drugs of this class, sertraline (ST) is the antidepressant therapy recommended most frequently. Therefore, this study aimed to evaluate the impact of gestational ST treatment on reproductive parameters and toxicological target organs of rat female offspring, as well as on somatic, reflex and neurobehavioral development, in a model of maternal adversity. Pregnant Wistar rats received vehicle (filtered water) or ST hydrochloride (20 mg/Kg/day diluted in vehicle) by oral gavage, associated or not with restraint stress for 1 h/day from gestational days 13-20. F1 female offspring was evaluated on reproductive parameters, body weight and somatic and reflex milestones from postnatal day (PND) 1. On PNDs 25 and 72, the elevated-plus-maze test was performed, while toxicological target organs were evaluated on PNDs 42 and 80. In utero exposure to ST, regardless of exposure to stress, reduced body weight at birth and affected the somatic development and estrous cycle. The absolute and relative thyroid weights were increased in Stress/ST group during puberty and adulthood, while the percentage of ovarian structures and the absolute uterine weight were altered in this group on PND 80. Prenatal exposure only to ST reduced initial body weight gain, delayed fur development and increased anxiety-like behavior on PND 25. Thus, this experimental study suggests that intrauterine exposure to ST disrupts the fetal environment and can negatively program serotonin-regulated processes. Furthermore, it impacts thyroid weight when associated with stress.

Exposure of pregnant rats to stress and/or sertraline: Side effects on maternal health and neurobehavioral development of male offspring.

AIMS: Sertraline (SE) is one of the most prescribed medications for treating gestational depression, anxiety and stress. However, little is known about its effects on nervous-system development in offspring. Therefore, this study investigated the somatic, reflex and neurobehavioral development of rats exposed to SE during pregnancy, associated or not with stress. MAIN METHODS: Pregnant Wistar rats were assigned to the following groups (n = 10-8 rats/group): CO - control animals administered filtered water by gavage; SE - animals administered 20 mg/kg SE by gavage; ST - animals subjected to restraining stress and administered filtered water; ST/SE - animals subjected to restraining stress and administered 20 mg/kg SE. The treatment was administered between gestational days (GD) 13 to 20. Somatic and reflex developments were investigated in the male offspring from postnatal day (PND) 1 to 21. The elevated plus maze was performed on PND 25 and 80. The open field and light/dark box test were performed on PND 90 and 100, respectively. KEY FINDINGS: Body weight reduction and vaginal bleeding were observed in pregnant rats exposed to SE. The male offspring of the SE group showed delay in incisor eruption, fur development and negative geotaxis. In addition, the SE group was less exploratory (anxious personality) compared to the CO and ST groups. SIGNIFICANCE: The results obtained in the present study demonstrate that sertraline not only impairs maternal health, but also, associated or not with stress, can compromise the somatic, reflex and neurobehavioral development of male rats.