PMID- 36396078
OWN - NLM
STAT- MEDLINE
DCOM- 20221216
LR  - 20221222
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 223
DP  - 2023 Feb 1
TI  - Impact of prenatal amoxicillin exposure on hippocampal development deficiency.
PG  - 109331
LID - S0028-3908(22)00390-2 [pii]
LID - 10.1016/j.neuropharm.2022.109331 [doi]
AB  - 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/beta-catenin pathway may suggest that the key role of SOX2/Wnt/beta-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.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Qin, Jiaxin
AU  - Qin J
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China; Department of Pediatrics, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Yao, Baozhen
AU  - Yao B
AD  - Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, China; 
      Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
FAU - Xie, Lulu
AU  - Xie L
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China; Department of Pediatrics, Renmin Hospital of Wuhan University, 
      Wuhan, China.
FAU - Wang, Tingting
AU  - Wang T
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
FAU - Zhang, Shuai
AU  - Zhang S
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
FAU - Luo, Mingcui
AU  - Luo M
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan, China.
FAU - Xu, Dan
AU  - Xu D
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China; Department of Pharmacy, Zhongnan Hospital of Wuhan University, School of 
      Pharmaceutical Sciences, Wuhan University, Wuhan, China. Electronic address: 
      xuyidan70188@whu.edu.cn.
FAU - Peng, Biwen
AU  - Peng B
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China; Department of Physiology, School of Basic Medical Sciences, Wuhan 
      University, Wuhan, China. Electronic address: pengbiwen@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20221114
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (beta Catenin)
RN  - 804826J2HU (Amoxicillin)
RN  - Kunming mice
SB  - IM
MH  - Mice
MH  - Animals
MH  - Female
MH  - Humans
MH  - Pregnancy
MH  - *beta Catenin/metabolism
MH  - *Prenatal Exposure Delayed Effects/metabolism
MH  - Amoxicillin/toxicity/metabolism
MH  - Hippocampus
OTO - NOTNLM
OT  - Amoxicillin
OT  - Glial cells
OT  - Hippocampus
OT  - Medication safety during pregnancy
OT  - Neurons
OT  - Toxicity window
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/11/18 06:00
MHDA- 2022/12/15 06:00
CRDT- 2022/11/17 19:33
PHST- 2022/09/25 00:00 [received]
PHST- 2022/11/01 00:00 [revised]
PHST- 2022/11/08 00:00 [accepted]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/11/17 19:33 [entrez]
AID - S0028-3908(22)00390-2 [pii]
AID - 10.1016/j.neuropharm.2022.109331 [doi]
PST - ppublish
SO  - Neuropharmacology. 2023 Feb 1;223:109331. doi: 10.1016/j.neuropharm.2022.109331. 
      Epub 2022 Nov 14.