The role of the placenta in transmitting disturbed serotonin levels from the maternal environment: A comparative study with live-bearing fish, rats and humans

The use of antidepressants during pregnancy may have negative consequences for the developing offspring. The antidepressant fluoxetine enhances extracellular serotonin concentrations. A disturbance in these serotonin concentrations during development may contribute to the adverse effects found in the offspring. The placenta plays an important role in providing nutrients and protection the fetus from toxic substances. In this thesis the role of the placenta in transmitting these adverse effects has been studied. First, the influence of fluoxetine on the placental transcriptome (the expression patterns of all genes) was studied. Both human placentas and the placentas of rats treated with fluoxetine during pregnancy were used. In the human study, a large number of genes were found to be differentially expressed in the placentas of women who had taken fluoxetine and who were pregnant with a boy. In the placentas of rats, the number of differentially expressed genes was smaller. Therefore, it seems likely that maternal depression influences the fluoxetine-induced changes in the placenta. To further investigate the role of the placenta in transmitting fluoxetine effects to the offspring, two closely related fish species, one with and one without a placenta, were compared. Fluoxetine treatment during pregnancy resulted in stronger adverse effects in offspring with the placenta than without the placenta. In conclusion, these results imply that the placenta plays an important role in the effects of fluoxetine on the offspring.