PMID- 36796495
OWN - NLM
STAT- MEDLINE
DCOM- 20230307
LR  - 20230320
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 463
DP  - 2023 Mar 15
TI  - Stage-, dose-, and course-dependent inhibition of prenatal amoxicillin exposure 
      on fetal articular cartilage development in fetal mice.
PG  - 116429
LID - S0041-008X(23)00067-4 [pii]
LID - 10.1016/j.taap.2023.116429 [doi]
AB  - Amoxicillin is widely used in the treatment of infectious diseases during 
      pregnancy; however, the effects of prenatal amoxicillin exposure (PAE) on fetal 
      development remain largely unknown. Therefore, this study aimed to investigate 
      the toxic effects of PAE on fetal cartilage at different stage-, dose-, and 
      course. Pregnant Kunming mice were orally administered 300 mg/kg.d (converted 
      from clinical dose) amoxicillin on gestational days (GD) 10-12 or 16-18 (mid or 
      late pregnancy stage), 150 or 300 mg/kg.d amoxicillin on GD16-18 (different 
      doses), 300 mg/kg.d amoxicillin on GD16 (single course) or 16-18 (multiple 
      courses), respectively. The fetal articular cartilage of the knee was collected 
      on GD18. The number of chondrocytes and the expression of matrix 
      synthesis/degradation, proliferation/apoptosis-related markers, and the TGF-beta 
      signaling pathway were detected. The results showed that the number of 
      chondrocytes and the expression of matrix synthesis markers were reduced in male 
      fetal mice treated with PAE (GD16-18, 300 mg/kg.d, single course and multiple 
      courses), whereas the above indices in female mice showed no changes. The 
      inhibited expression of PCNA, increased expression of Caspase-3, and 
      down-regulated expression of the TGF-beta signaling pathway were found in male PAE 
      fetal mice. Accordingly, PAE exerted its "toxic effect window" on the knee 
      cartilage development in male fetal mice, which manifested as reduced chondrocyte 
      number and inhibited expression of matrix synthesis at a clinical dose of 
      multiple courses in the late pregnancy stage. This study provides a theoretical 
      and experimental basis for elucidating the risk of chondrodevelopmental toxicity 
      associated with amoxicillin during pregnancy.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Gu, Hanwen
AU  - Gu H
AD  - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, 
      Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key 
      Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
FAU - Li, Bin
AU  - Li B
AD  - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, 
      Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key 
      Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
FAU - Liu, Liang
AU  - Liu L
AD  - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, 
      Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key 
      Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
FAU - Li, Xufeng
AU  - Li X
AD  - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, 
      Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key 
      Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally 
      Originated Disease, Wuhan 430071, China. Electronic address: 
      wanghui19@whu.edu.cn.
FAU - Chen, Liaobin
AU  - Chen L
AD  - Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, 
      Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key 
      Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic 
      address: lbchen@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230214
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Transforming Growth Factor beta)
RN  - Kunming mice
SB  - IM
MH  - Mice
MH  - Animals
MH  - Pregnancy
MH  - Male
MH  - Female
MH  - *Cartilage, Articular
MH  - Fetus/metabolism
MH  - Fetal Development
MH  - Transforming Growth Factor beta/metabolism
MH  - Chondrocytes
OTO - NOTNLM
OT  - Amoxicillin
OT  - Articular cartilage development
OT  - Gender differences
OT  - Prenatal exposure
OT  - Synthesis of extracellular matrix
COIS- Declaration of Competing Interest All the authors state that they have no 
      conflicts of interest.
EDAT- 2023/02/17 06:00
MHDA- 2023/03/08 06:00
CRDT- 2023/02/16 19:24
PHST- 2022/10/13 00:00 [received]
PHST- 2023/01/20 00:00 [revised]
PHST- 2023/02/12 00:00 [accepted]
PHST- 2023/02/17 06:00 [pubmed]
PHST- 2023/03/08 06:00 [medline]
PHST- 2023/02/16 19:24 [entrez]
AID - S0041-008X(23)00067-4 [pii]
AID - 10.1016/j.taap.2023.116429 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2023 Mar 15;463:116429. doi: 10.1016/j.taap.2023.116429. 
      Epub 2023 Feb 14.