PMID- 35917869
OWN - NLM
STAT- MEDLINE
DCOM- 20220824
LR  - 20220914
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 203
DP  - 2022 Sep
TI  - Low miR-92a-3p in oocytes mediates the multigenerational and transgenerational 
      inheritance of poor cartilage quality in rat induced by prenatal dexamethasone 
      exposure.
PG  - 115196
LID - S0006-2952(22)00290-8 [pii]
LID - 10.1016/j.bcp.2022.115196 [doi]
AB  - An adverse environment during pregnancy leads to intrauterine programming changes 
      in multiple generations, resulting in the multigenerational inheritance of 
      abnormal phenotype. Here, we reported the multigenerational inheritance of poor 
      articular cartilage quality induced by prenatal dexamethasone exposure (PDE) with 
      0.2 mg/kg.d dexamethasone from gestational day (GD) 9 to GD20 in Wistar rats and 
      investigated its intrauterine epigenetic programming mechanism. For the F1 female 
      offspring at GD20, we found that the matrix synthesis of cartilage was 
      suppressed, the histone 3 lysine 9 acetylation (H3K9ac) level and mRNA expression 
      of the TGFbeta signaling pathway were decreased, and the expression of histone 
      deacetylase (HDAC) 2 was increased in the cartilage. Meaningfully, the similar 
      changes were also found in the F1-F3 female adult offspring. Furthermore, PDE 
      decreased the expression of miR-92a-3p in the oocytes of the F1-F2 offspring and 
      in the cartilage of the F1-F3 generations. In vitro, the effect of dexamethasone 
      on chondrocytes revealed that it inhibited the expression of miR-92a-3p through 
      activating and binding glucocorticoid receptor, and reduced the H3K9ac level in 
      the promoter of the TGFbeta signaling pathway through the increased HDAC2. In 
      conclusion, PDE induces the multigenerational inheritance of poor articular 
      cartilage quality in female adult offspring; the potential mechanism involves the 
      intergenerational effect of low miR-92a-3p expression in oocytes and low 
      functional programming of TGFbeta signaling pathway induced by decreased H3K9ac 
      level via upregulating HDAC2. This study provides a new perspective to explain 
      the multi-generation inheritance of PDE-induced organ dysplasia in adult 
      offspring.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Tie, Kai
AU  - Tie K
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Zhao, Zhe
AU  - Zhao Z
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Wu, Zhixin
AU  - Wu Z
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China.
FAU - Qin, Jun
AU  - Qin J
AD  - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      430071, China; Hubei Provincial Key Laboratory of Developmentally Originated 
      Disease, Wuhan 430071, China.
FAU - Zhang, Jinzhi
AU  - Zhang J
AD  - Department of pharmacology, Wuhan University TaiKang Medical School (School of 
      Basic Medical Sciences), Wuhan 430071, China.
FAU - Pei, Linguo
AU  - Pei L
AD  - Department of pharmacology, Wuhan University TaiKang Medical School (School of 
      Basic Medical Sciences), Wuhan 430071, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of pharmacology, Wuhan University TaiKang Medical School (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  - 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 - 20220730
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (MicroRNAs)
RN  - 0 (Transforming Growth Factor beta)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - *Cartilage, Articular/metabolism
MH  - Dexamethasone/toxicity
MH  - Female
MH  - Humans
MH  - *MicroRNAs/metabolism
MH  - Oocytes/metabolism
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects/chemically induced/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Transforming Growth Factor beta/metabolism
OTO - NOTNLM
OT  - Fetal programming
OT  - Histone acetylation
OT  - Multigeneration inheritance
OT  - Poor articular cartilage quality
OT  - Prenatal dexamethasone exposure
OT  - TGFbeta signaling pathway
EDAT- 2022/08/03 06:00
MHDA- 2022/08/25 06:00
CRDT- 2022/08/02 19:13
PHST- 2022/05/14 00:00 [received]
PHST- 2022/07/23 00:00 [revised]
PHST- 2022/07/26 00:00 [accepted]
PHST- 2022/08/03 06:00 [pubmed]
PHST- 2022/08/25 06:00 [medline]
PHST- 2022/08/02 19:13 [entrez]
AID - S0006-2952(22)00290-8 [pii]
AID - 10.1016/j.bcp.2022.115196 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2022 Sep;203:115196. doi: 10.1016/j.bcp.2022.115196. Epub 2022 
      Jul 30.