Impact of prenatal amoxicillin exposure on hippocampal development deficiency

Jiaxin Qin1, Baozhen Yao2, Lulu Xie1

  • 1Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China; Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, China.

Neuropharmacology
|November 17, 2022
PubMed

Insights

Prenatal amoxicillin exposure (PAmE) can harm fetal hippocampal development, causing cell damage and impaired function. Even safe doses may pose risks, highlighting the need for cautious antibiotic use during pregnancy.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pharmacology

Background:

  • Amoxicillin is commonly used during pregnancy.
  • Prenatal amoxicillin exposure (PAmE) may cause offspring developmental disorders, asthma, and kidney damage.
  • The specific effects of PAmE on fetal hippocampal neurodevelopment remain unclear.

Purpose of the Study:

  • To investigate the effects of PAmE on fetal hippocampal development and function.
  • To explore the underlying molecular mechanisms of PAmE-induced hippocampal damage.

Main Methods:

  • Pregnant mice received amoxicillin via intragastric administration at various stages, doses, and courses.
  • Hippocampal tissues from gestational day 18 offspring were analyzed for morphology and function.
  • Molecular mechanisms involving key genes and pathways were examined.

Main Results:

  • PAmE led to hippocampal hypoplasia, reduced neuronal proliferation, and impaired synaptic plasticity.
  • Hippocampal astrocytes and microglia showed varying degrees of damage.
  • The severity of toxicity depended on the timing, dose, and duration of amoxicillin exposure, with late gestation, high dose, and multi-course treatments causing the most damage.
  • Reduced SOX2 and Wnt/β-catenin pathway gene expression were observed, suggesting their role in impaired hippocampal development.

Conclusions:

  • PAmE is developmentally toxic to the fetal hippocampus, affecting various hippocampal cells.
  • Potential hippocampal damage to offspring may occur even with clinically approved amoxicillin doses.
  • This study provides a basis for rational drug use during pregnancy and risk assessment of fetal hippocampal developmental toxicity.
Abstract