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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.
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.
Background:
Amoxicillin has been widely used to treat infectious diseases during pregnancy. Current studies suggest that amoxicillin exposure during pregnancy could lead to developmental disorders in the offspring and increase the incidence of long-term complications such as asthma and kidney damage in adulthood. However, the adverse effects of prenatal amoxicillin exposure (PAmE) including administration stage, doses and courses on fetal hippocampal neurodevelopment and its function in the offspring have not been elucidated. In this study, we intend to investigate the effects of PAmE on fetal hippocampal development and its possible mechanisms.
Method:
Pregnant Kunming mice were given intragastric administration with amoxicillin at different administration stage, doses and courses, and GD (gestational day) 18 offspring hippocampus was collected for morphological and development-related functional assays, and the molecular mechanisms were explored.
Results:
PAmE induced hippocampal hypoplasia in the offspring with suppressed hippocampal neuronal cell proliferation and impaired neuronal synaptic plasticity comparatively; hippocampal astrocyte and microglia were damaged to varying degrees. The developmental toxicity of PAmE in fetal mices varies by time, dose, and course of treatment. The most severe damage was observed in the late gestation, high dose, and multi-course dosing groups. The significant reduction either in SOX2, an essential gene in regulating neural progenitor cell proliferation, and reduction of genes related to the Wnt/β-catenin pathway may suggest that the key role of SOX2/Wnt/β-catenin pathway in impaired hippocampal development in the offspring due to PAmE.
Conclusion:
In this study, PAmE was found to be developmentally toxic to the hippocampus thus to induce developmental damage to various hippocampal cells; Even with current clinically safe doses, potential hippocampal damage to offspring may still present; This study provides a theoretical and experimental basis for guiding the rational usage of drugs during pregnancy and giving effectively assessment of the risk on fetal hippocampal developmental toxicity.
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