PMID- 34697420
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20230602
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 43
IP  - 6
DP  - 2022 Jun
TI  - Prenatal dexamethasone exposure programs the decreased testosterone synthesis in 
      offspring rats by low level of endogenous glucocorticoids.
PG  - 1461-1472
LID - 10.1038/s41401-021-00789-z [doi]
AB  - Prenatal dexamethasone exposure (PDE) can decrease maternal endogenous 
      glucocorticoid level and induce testicular dysplasia in male offspring rats. In 
      this study we investigated low level endogenous glucocorticoid-mediated 
      testicular dysplasia in PDE offspring and elucidated the intrauterine epigenetic 
      programming mechanisms. Pregnant rats were injected with dexamethasone 
      (0.2 mg.kg(-1).d(-1), sc) on gestational day (GD) 9-20. The offspring rat blood 
      and testis were collected after euthanasia on GD20, postnatal week (PW) 12 or 
      PW28. We showed that PDE induced abnormal morphology of testis and significantly 
      decreased the expression of testosterone synthesis-related genes as well as 
      testosterone production before and after birth. Meanwhile, serum corticosterone, 
      the expression and histone 3 lysine 14 acetylation (H3K14ac) of testicular 
      insulin-like growth factor 1 (IGF1) were significantly decreased. After the 
      pregnant rats were subjected to chronic stress for 2 weeks (PW10-12), serum 
      corticosterone level was increased in the adult PDE offspring, and the 
      above-mentioned other indicators were also improved. Cultured Leydig cells (TM3) 
      were treated with corticosterone (62.5-500 nM) in vitro. We showed that 
      corticosterone concentration-dependently inhibited glucocorticoid receptor alpha 
      (GRalpha) and miR-124-3p expression, increased histone deacetylase 5 (HDAC5) 
      expression, and decreased IGF1 H3K14ac level and the expression of 
      IGF1/steroidogenic acute regulatory protein (StAR), suggesting that 
      corticosterone at lower than physiological level (<500 nM) inhibited testosterone 
      synthesis by reducing H3K14ac and the expression level of IGF1 through 
      GRalpha/miR-124-3p/HDAC5 pathway. In conclusion, PDE can cause persistent inhibition 
      of testosterone synthesis before and after birth in the offspring rats by low 
      level of endogenous glucocorticoids.
CI  - (c) 2021. The Author(s), under exclusive licence to CPS and SIMM.
FAU - Liu, Min
AU  - Liu M
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      430071, China.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Pei, Lin-Guo
AU  - Pei LG
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      430071, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Xiao, Hao
AU  - Xiao H
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Chen, Ya-Wen
AU  - Chen YW
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China. wanghui19@whu.edu.cn.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      430071, China. wanghui19@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20211025
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Glucocorticoids)
RN  - 0 (MIRN124 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 3XMK78S47O (Testosterone)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 3.5.1.98 (Hdac5 protein, rat)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Corticosterone
MH  - Dexamethasone/pharmacology
MH  - Female
MH  - Glucocorticoids
MH  - Histone Deacetylases
MH  - Humans
MH  - Male
MH  - *MicroRNAs
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Wistar
MH  - Testosterone
PMC - PMC9159998
OTO - NOTNLM
OT  - Leydig cells (TM3)
OT  - dexamethasone
OT  - endogenous glucocorticoids
OT  - epigenetic modification
OT  - insulin-like growth factor 1
OT  - prenatal exposure
OT  - steroidogenic acute regulatory protein
OT  - testis
OT  - testosterone synthesis
COIS- The authors declare no competing interests.
EDAT- 2021/10/27 06:00
MHDA- 2022/06/07 06:00
PMCR- 2023/06/01
CRDT- 2021/10/26 06:20
PHST- 2021/05/19 00:00 [received]
PHST- 2021/09/29 00:00 [accepted]
PHST- 2021/10/27 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2021/10/26 06:20 [entrez]
PHST- 2023/06/01 00:00 [pmc-release]
AID - 10.1038/s41401-021-00789-z [pii]
AID - 789 [pii]
AID - 10.1038/s41401-021-00789-z [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2022 Jun;43(6):1461-1472. doi: 10.1038/s41401-021-00789-z. 
      Epub 2021 Oct 25.