Abstract
The use of antidepressant treatment during pregnancy is increasing, and selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressants in pregnant women. Serotonin plays a role in embryogenesis, and serotonin transporters are expressed in two-cell mouse embryos. Thus, the aim of the present study was to evaluate whether fluoxetine, one of the most prescribed SSRI antidepressant world-wide, exposure influences the timing of different embryo developmental stages, and furthermore, to analyze what protein, and protein networks, are affected by fluoxetine in the early embryo development. Human embryos (n = 48) were randomly assigned to treatment with 0.25 or 0.5 μM fluoxetine in culture medium. Embryo development was evaluated by time-lapse monitoring. The fluoxetine-induced human embryo proteome was analyzed by shotgun mass spectrometry. Protein secretion from fluoxetine-exposed human embryos was analyzed by use of high-multiplex immunoassay. The lower dose of fluoxetine had no influence on embryo development. A trend toward reduced time between thawing and start of cavitation was noted in embryos treated with 0.5 μM fluoxetine (p = 0.065). Protein analysis by shotgun mass spectrometry detected 45 proteins that were uniquely expressed in fluoxetine-treated embryos. These proteins are involved in cell growth, survival, proliferation, and inflammatory response. Culturing with 0.5 μM, but not 0.25 μM fluoxetine, caused a significant increase in urokinase-type plasminogen activator (uPA) in the culture medium. In conclusion, fluoxetine has marginal effects on the timing of developmental stages in embryos, but induces expression and secretion of several proteins in a manner that depends on dose. For these reasons, and in line with current guidelines, the lowest possible dose of SSRI should be used in pregnant women who need to continue treatment.
Highlights
The prevalence of major depression during pregnancy is approximately 3–5% (Andersson et al, 2003; Gavin et al, 2005)
Based on the established role for 5-HT in embryogenesis (Lauder and Krebs, 1978; Lauder et al, 1981; reviewed in Buznikov et al, 2001), and the fact that serotonin transporters are expressed in early mouse embryos (Amireault and Dube, 2005), we hypothesized that the fetus may be affected though direct exposure to SSRIs
In this study we demonstrate that fluoxetine has a marginal influence on early human embryo development in culture
Summary
The prevalence of major depression during pregnancy is approximately 3–5% (Andersson et al, 2003; Gavin et al, 2005). Fluoxetine and Human Embryo Development (Barbey and Roose, 1998; Gentile, 2005), SSRI treatment has been associated with increased risk of pregnancy complications such as preterm birth and preeclampsia (Qiu et al, 2009; Wisner et al, 2009). SSRIs have been associated with cardiac malformations (Olivier et al, 2013; El Marroun et al, 2014; see Furu et al, 2015) and increased risk of persistent pulmonary hypertension, these conditions are rare (Wogelius et al, 2006; Kieler et al, 2012). Other studies suggest that these malformations and behavioral defects may be caused by the underlying depression and not by the treatment itself (reviewed in Olivier et al, 2013, 2015a; Waters et al, 2014)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
