Maternal administration of APAP induces angiogenesis disorders in mouse placenta via SOCS3/JAK1/STAT3 pathway.
Reprod Toxicol
; 129: 108668, 2024 10.
Article
in En
| MEDLINE
| ID: mdl-39032760
ABSTRACT
Acetaminophen (APAP, also known as paracetamol) is a commonly used antipyretic and analgesic that is considered safe to use during pregnancy. However, a growing body of research indicates that gestational administration of APAP increased the risk of neurodevelopmental, reproductive and genitourinary disorders in offspring, alongside impairments in placental development. Notably, over-dosed APAP exhibits direct toxicity to endothelial cells, but there is very limited research investigating the impact of APAP on placental angiogenesis, a gap we aim to address in this study. Pregnant mice were gavaged with APAP (15, 50 and 150â¯mg/kg/d) from embryonic day 11.5 (E11.5) to E13.5. Administration of 150â¯mg/kg/d APAP leads to low birth weight (LBW) of the offspring and disordered vascular structures within the labyrinthine (Lab) layer of the placenta. This disruption is accompanied by a significant increase in Suppressor of Cytokine Signaling 3 (SOCS3) level, a negative regulator of the Janus kinase signal transducer 1 and activator of the transcription 3 (JAK1/STAT3) signaling. Meanwhile, Human umbilical vein endothelial Cells (HUVECs) with the treatment of 3â¯mM APAP exhibited reduced cell viability, whereas 1â¯mM APAP significantly affected the proliferation, migration, invasion and angiogenic capacities of HUVECs. Further, SOCS3 was up-regulated in HUVECs, accompanied by inhibition of JAK1/STAT3 pathways. Knocking-down SOCS3 in HUVECs restored the nuclear translocation of STAT3 and efficiently promoted cellular capacity of tube formation. Overall, short-term maternal administration of overdosed APAP impairs angiogenic capacities of fetal endothelial cells via SOCS3/JAK1/STAT3 pathway in the mouse placenta. This study reveals that overdose of APAP during pregnancy may adversely affect placental angiogenesis, emphasizing the importance of adhering to the safe principles of smallest effective dose for the shortest required durations.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Placenta
/
Signal Transduction
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STAT3 Transcription Factor
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Janus Kinase 1
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Human Umbilical Vein Endothelial Cells
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Suppressor of Cytokine Signaling 3 Protein
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Acetaminophen
Limits:
Animals
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Female
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Humans
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Pregnancy
Language:
En
Journal:
Reprod Toxicol
Journal subject:
EMBRIOLOGIA
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MEDICINA REPRODUTIVA
/
TOXICOLOGIA
Year:
2024
Document type:
Article
Country of publication: