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Title: Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

Hypothesis: 10–15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown. Methods: Female nulliparous Wistar rats were given vehicle (N = 15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N = 15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring. Results: Fluoxetine exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1). Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use duringmore » pregnancy. Conclusion: These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations. - Highlights: • Antenatal exposure to fluoxetine results in postnatal adiposity in the offspring. • Offspring exposed to fluoxetine have abnormal glycemic control in adulthood. • Maternal exposure to fluoxetine causes fatty liver in the offspring.« less
Authors:
;  [1] ; ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [1]
  1. Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1 (Canada)
  2. Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1 (Canada)
  3. Department of Obstetrics and Gynecology, Physiology and Pharmacology, University of Western, London, ON N6A 3K6 (Canada)
  4. Department of Pediatrics, McMaster University, Hamilton, ON L8S 4K1 (Canada)
  5. Department of Psychiatry, University of Toronto, Toronto, ON M5S 1A1 (Canada)
  6. Department of Medicine, McMaster University, Hamilton, ON L8S 4K1 (Canada)
Publication Date:
OSTI Identifier:
22465757
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 285; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIDEPRESSANTS; CARBON DIOXIDE; CHILDREN; CHOLESTEROL; DNA; GLUCOSE; HAZARDS; HOMEOSTASIS; HUMAN POPULATIONS; HYDROXYLASES; HYPOTHESIS; INFLAMMATION; LIVER; MACROPHAGES; METABOLIC DISEASES; MONOCYTES; PREGNANCY; RATS; SEROTONIN; VISIBLE RADIATION; WOMEN