In Utero and Lactational Exposure to Fluoxetine in Wistar Rats: Pregnancy Outcomes and Sexual Development

• Published in: Basic & clinical pharmacology & toxicology Vol. 113; no. 2; pp. 132 - 140
• Main Authors: Müller, Juliane C., Boareto, Ana C., Lourenço, Emerson L. B., Zaia, Renata M., Kienast, Mariana F., Spercoski, Katherinne M., Morais, Rosana N., Martino‐Andrade, Anderson J., Dalsenter, Paulo R.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01-08-2013; Wiley Subscription Services, Inc
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Body Weight; Dose-Response Relationship, Drug; Estrogens - metabolism; Female; Fluoxetine - administration & dosage; Fluoxetine - adverse effects; Lactation; Male; Maternal Exposure - adverse effects; Medical sciences; Pharmacology. Drug treatments; Pregnancy; Pregnancy Outcome - veterinary; Progestins - metabolism; Rats; Rats, Wistar; Reproduction - drug effects; Sexual Development - drug effects; Prognosis; Serotonin; Rat; Fluoxetine; Psychotropic; Rodentia; Exposure; Reuptake inhibitor; Breast feeding; In utero; Selective serotonin reuptake inhibitor; Pregnancy; Vertebrata; Mammalia; Animal; Neurotransmitter; Development; Antidepressant agent; Female
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.12072

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.