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The serotonin reuptake inhibitor fluoxetine induces human fetal membrane sterile inflammation through p38 MAPK activation.

Authors :
Fabrizio VA
Lindsay CV
Wilcox M
Hong S
Lynn T
Norwitz ER
Yonkers KA
Abrahams VM
Source :
Journal of reproductive immunology [J Reprod Immunol] 2023 Feb; Vol. 155, pp. 103786. Date of Electronic Publication: 2022 Dec 13.
Publication Year :
2023

Abstract

Serotonin Reuptake Inhibitors (SRIs) are often used as first line therapy for depression and other psychiatric disorders. SRI use during pregnancy is associated with preterm premature rupture of membranes (PPROM) and subsequent preterm birth. The objective of this study was to investigate the mechanism(s) responsible for SRI-associated PPROM. Putative mechanisms underlying PPROM include fetal membrane (FM) inflammation, increased apoptosis, and/or accelerated senescence, the later which may be reversed by statins. Human FM explants from normal term deliveries without labor, infection, or antidepressant use were treated with or without the SRI, fluoxetine (FLX), either alone or in the presence of a p38 MAPK inhibitor or the statins, simvastatin or rosuvastatin. FMs were also collected from women either unexposed or exposed to FLX during pregnancy. FLX significantly increased FM p38 MAPK activity and secretion of inflammatory IL-6. Inhibition of p38 MAPK reduced FM IL-6 secretion in response to FLX. Statins did not reduce the SRI-induced FM IL-6 production. FMs from women exposed to FLX during pregnancy expressed elevated levels of p38 MAPK activity compared to matched unexposed women. FMs exposed to FLX did not exhibit signs of increased apoptosis and/or accelerated senescence. These results indicate that the SRI, FLX, may induce sterile FM inflammation during pregnancy through activation of the p38 MAPK pathway, and in the absence of apoptosis and senescence. These findings may better inform clinicians and patients as they weigh the risks and benefits of SRI antidepressant treatment during pregnancy.<br /> (Copyright © 2022 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1872-7603
Volume :
155
Database :
MEDLINE
Journal :
Journal of reproductive immunology
Publication Type :
Academic Journal
Accession number :
36528909
Full Text :
https://doi.org/10.1016/j.jri.2022.103786