Prenatal paroxetine dysregulates monoamine homeostasis and affects placental hemodynamics in the rat fetoplacental unit
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10505094" target="_blank" >RIV/00216208:11160/25:10505094 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=EC64Ddrh.c" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=EC64Ddrh.c</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.biopha.2025.118680" target="_blank" >10.1016/j.biopha.2025.118680</a>
Alternative languages
Result language
angličtina
Original language name
Prenatal paroxetine dysregulates monoamine homeostasis and affects placental hemodynamics in the rat fetoplacental unit
Original language description
Antidepressant use during pregnancy is increasingly common, with selective serotonin reuptake inhibitors (SSRIs) widely prescribed for maternal depression. However, growing evidence links prenatal SSRI exposure to adverse outcomes, including impaired placental functions, disrupted fetal development, and long-term neurobehavioral risks. Monoamines such as serotonin, dopamine, and norepinephrine are critical regulators of placental vascular tone, fetal programming, and neurodevelopment, making them highly susceptible to pharmacological disruption. Here, we investigated the effects of prenatal paroxetine on monoamine regulation, metabolite profiles, and fetoplacental hemodynamics in a pregnant rat model. Paroxetine was administered orally at two doses, 15 mg/kg (n = 10) or 50 mg/kg (n = 7) and compared to controls (n = 6). Gene expression of monoamine-related transporters and enzymes was quantified in placenta and fetal brain by qRT-PCR. Placental and fetal brain metabolomes were assessed via LC-MS, and Doppler ultrasound was used to evaluate uterine and fetal vascular parameters. At 15 mg/kg, paroxetine reduced fetal (2.03 +- 1.10 g vs. 2.27 +- 0.92 g) and placental weights (0.35 +- 0.08 g vs. 0.46 +- 0.05 g), downregulated placental expression of serotonin, dopamine, and norepinephrine transporters, disrupted tryptophan metabolism, and increased vascular resistance in umbilical arteries (2.10 +- 0.21 vs. 1.85 +- 0.05). Surprisingly, the 50 mg/kg dose attenuated many of these effects, suggesting non-linear pharmacological response, potentially due to transporter saturation and/or receptor desensitization. Importantly, gene expression and hemodynamic effects were consistent across sexes. These findings provide novel mechanistic insights into the impact of SSRIs on placental function and fetal development, underscoring the complexity of their pharmacokinetics and pharmacodynamics during pregnancy and emphasizing the need for careful dose consideration during pregnancy.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomedicine & Pharmacotherapy
ISSN
0753-3322
e-ISSN
1950-6007
Volume of the periodical
192
Issue of the periodical within the volume
November
Country of publishing house
FR - FRANCE
Number of pages
11
Pages from-to
118680
UT code for WoS article
999
EID of the result in the Scopus database
2-s2.0-105020878919