This study evaluated the reproductive effects of fluoxetine exposure in utero and during lactation on pregnancy outcomes and the sexual development of offspring. Pregnant Wistar rats were treated daily with fluoxetine (0.4, 1.7 and 17 mg/kg/ day) or distilled water by gavage from gestation day (GD) 7 to lactation day (LD) 21. A significant reduction in maternal body weight was observed during pregnancy and lactation in dams exposed to 17 mg/kg fluoxetine. Hormone analysis revealed an increase in progestagen and glucocorticoid metabolites on GD 15 and oestrogen and progestagen metabolites on LD 7 in dams treated with 17 mg/kg fluoxetine. Oestrogen metabolites also were increased on LD 7 in dams treated with 0.4 mg/kg fluoxetine. Besides that, an increase in the weight of the adrenal glands and a reduction in uterine weight in dams exposed to highest dose of fluoxetine were observed. Finally, pup birthweight and the viability and weaning indices also were reduced in animals exposed to 17 mg/kg fluoxetine. Overall, maternal hormonal changes were only observed at the highest dose tested, which also induced maternal and foetal toxicity. No significant changes were seen in dams or offspring exposed to therapeutic-like doses.Major depressive disorder is one of the most widespread and debilitating forms of mental illness, characterized by behavioural, affective, cognitive and somatic symptoms [1]. Epidemiological studies have shown that, in women, depression is the major cause of disease-related disability worldwide [2], with an increased prevalence during reproductive age, especially during pregnancy (10%) and after childbirth (20%) [3,4].The past decade has seen a large increase in the use of selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and lactation. Among these, fluoxetine was the most widely used antidepressant during pregnancy [5,6]. In this context, it is important to consider that fluoxetine crosses the placenta [7], reaching similar levels in maternal and foetal serum. In addition, fluoxetine is also secreted into breast milk during lactation [8,9]. The possibility of perinatal exposure to fluoxetine has raised significant concerns about its possible adverse effects in mothers and infants. The pre-and early post-natal development of the reproductive system is under complex integrative control of the central nervous system, pituitary, gonads and genital tract, all of which are potential targets of transplacental and lactational chemical exposure [10]. Therefore, understanding the effects of fluoxetine on the reproductive system of the developing foetus/neonate and pregnant and nursing women is important.Investigations of the negative consequences of SSRI antidepressants during pregnancy and lactation are promising, but still with a lack of significant information on the spectrum of adverse effects and mode of action of these substances at different stages of animal and human development. According to the review by Ellfolk and Malm [11], clinical studies have revealed l...
