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The effects of antenatal depression and antidepressant treatment on placental gene expression
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Reproduktiv hälsa/Sundström Poromaa)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Obstetrisk forskning/Högberg)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Reproduktiv hälsa/Sundström Poromaa)ORCID iD: 0000-0002-4935-7532
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Reproduktiv hälsa/Sundström Poromaa)
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2015 (English)In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 8, 465- p.Article in journal (Refereed) Published
Abstract [en]

The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy. Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample. In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

Place, publisher, year, edition, pages
2015. Vol. 8, 465- p.
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-241985DOI: 10.3389/fncel.2014.00465ISI: 000349070400001OAI: oai:DiVA.org:uu-241985DiVA: diva2:781970
Available from: 2015-01-19 Created: 2015-01-19 Last updated: 2017-12-05Bibliographically approved
In thesis
1. The Effects of SSRI Treatment on Human Placenta and Embryo
Open this publication in new window or tab >>The Effects of SSRI Treatment on Human Placenta and Embryo
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During pregnancy, 4 - 7% of women suffer from major depressive disorder. When antidepressive treatment is needed, selective serotonin reuptake inhibitors (SSRIs) are the most commonly used. Although severe complications from SSRI treatment are rare, association with a number of adverse pregnancy and fetal outcomes has been found. Also, antenatal depression per se has been shown to affect pregnancy outcomes. The overall aim of this thesis was to examine the effects of SSRIs on human placenta and embryo.

In the first study, gene expression was investigated in placenta from depressed, SSRI-treated and healthy pregnant women, using microarray analysis. Antenatal depression and SSRI treatment induced alterations in gene expression, but only 20 genes in common were noted. Validation with qRT-PCR showed that six out of seven selected genes were altered in SSRI-treated women compared with controls, and two genes were altered between depressed women and controls.

In study two, the protein levels in placenta from depressed, SSRI-treated and healthy pregnant women were investigated, focusing on the NGF signaling pathway. NGF, phosphorylated Raf-1, ROCK2 and phosphorylated ROCK2, were altered in both SSRI-treated and depressed women, although the proteins were regulated differently in the two groups.

In the third study, human embryos were treated with fluoxetine. Embryo development and protein expression were studied. Fluoxetine had some effect on the timing of embryo developmental stages. Also, several proteins were uniquely found in fluoxetine-treated embryos compared with untreated embryos. Fluoxetine also altered the levels of proteins secreted from the embryo.

In the fourth study, the human neuroblastoma cell line SH-SY5Y/TrkA was treated with TPA and NGF. The activation of Raf-1 was investigated and the involvement of Ras and PKC was studied. Both NGF and TPA activated Raf-1, but to a different extent and via different pathways. The NGF-induced activation of Raf-1 was mediated via Ras, while TPA induced signaling via PKC.

In conclusion, SSRI treatment and antenatal depression influence placental gene and protein expression. These findings may affect placental development and function, which in turn could affect fetal development. Also, direct exposure of embryos to fluoxetine has some effects on embryo development and protein expression, which may affect the development of the fetus.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 90 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1095
Keyword
antenatal depression, embryo, embryo development, fluoxetine, gene expression, NGF, placenta, protein expression, Raf-1, ROCK, signaling pathways, SSRI
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Medical Science; Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-248527 (URN)978-91-554-9227-4 (ISBN)
Public defence
2015-05-28, Sal IV, Universitetshuset, Uppsala, 09:15 (Swedish)
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Supervisors
Available from: 2015-05-06 Created: 2015-03-31 Last updated: 2015-07-07

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Olivier, Jocelien D AÅkerud, HelenaSkalkidou, AlkistisKaihola, HelenaSundström-Poromaa, Inger

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