Developmental fluoxetine exposure affects adolescent and adult bone depending on the dose and period of exposure in mice

At the end of gestation, fetal skeleton rapidly accumulates calcium, and bone development continues in offspring postnatally. To accommodate, maternal skeletal physiology is modulated in a serotonin-dependent manner. Selective serotonin reuptake inhibitors (SSRIs) are generally considered safe for treatment of major depressive disorder, postpartum depression, and other psychiatric illnesses during the peripartum period, but because serotonin affects bone remodeling, SSRIs are associated with decreased bone mass across all ages and sexes, and the impact of SSRIs during fetal and postnatal development has not been fully investigated. In the present study, our aim was to examine developmental fluoxetine exposure on offspring skeleton and to assess varying degrees of impact depending on dose and window of exposure in short-term and long-term contexts. We established that a low dose of lactational fluoxetine exposure caused a greater degree of insult to offspring bone than either a low dose during fetal and postpartum development or a high dose during lactation only in mice. We further discovered lasting impacts of developmental fluoxetine exposure, especially during lactation only, on adult bone and body composition. Herein, we provide evidence fluoxetine exposure during early development may have detrimental effects on the skeleton of offspring at weaning and into adulthood.

Automated summary

At the end of gestation, fetal skeleton rapidly accumulates calcium, and bone development continues in offspring postnatally. Maternal skeletal physiology is modulated in a serotonin-dependent manner to accommodate this. Selective serotonin reuptake inhibitors (SSRIs), commonly used to treat major depressive disorder, postpartum depression, and other psychiatric illnesses, are associated with decreased bone mass due to their impact on serotonin, but their effects on fetal and postnatal development have not been fully studied. This study investigated the impact of developmental fluoxetine exposure on offspring skeleton and found that a low dose during lactation caused more damage to offspring bone than a low dose during fetal and postpartum development or a high dose during lactation only. Furthermore, lasting impacts of developmental fluoxetine exposure, especially during lactation only, on adult bone and body composition were discovered. This study provides evidence that early developmental fluoxetine exposure may have detrimental effects on the skeleton of offspring at weaning and into adulthood.