PMID- 29370380
OWN - NLM
STAT- MEDLINE
DCOM- 20181105
LR  - 20181105
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 159
IP  - 3
DP  - 2018 Mar 1
TI  - Prenatal Dexamethasone Exposure Induced Ovarian Developmental Toxicity and 
      Transgenerational Effect in Rat Offspring.
PG  - 1401-1415
LID - 10.1210/en.2018-00044 [doi]
AB  - Prenatal dexamethasone exposure (PDE) induces multiorgan developmental toxicities 
      in offspring. Here we verified the transgenerational inheritance effect of 
      ovarian developmental toxicity by PDE and explored its intrauterine programming 
      mechanism. Pregnant rats subcutaneously received 0.2 mg/kg/d dexamethasone from 
      gestational day (GD) 9 to GD20. A subgroup was euthanized for fetuses on GD20, 
      and the other group went on to spontaneous labor to produce F1 offspring. The 
      adult F1 females were mated with normal males to produce the F2 and F3 
      generations. The PDE fetal rats exhibited ovarian mitochondrial structural 
      abnormalities, decreased serum estradiol (E2) levels, and lower expression levels 
      of ovarian steroidogenic factor 1 (SF1), steroidal synthetases, and insulinlike 
      growth factor 1 (IGF1). On postnatal week (PW) 6 and PW12, the PDE F1 offspring 
      showed altered reproductive behavior and ovarian morphology. The serum E2 level 
      and ovarian expression of SF1, steroidal synthetases, and IGF1 were also 
      decreased. The adult F3 offspring showed alterations in reproductive phenotype 
      and ovarian IGF1, SF1, and steroidal synthetase expression similar to those of 
      F1. PDE induces ovarian developmental toxicity and transgenerational inheritance 
      effects. The mechanism by which this toxicity occurs may be related to 
      PDE-induced low-functional programming of fetal ovarian IGF1/SF1 and steroidal 
      synthetases.
FAU - Lv, Feng
AU  - Lv F
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
FAU - Wan, Yang
AU  - Wan Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
FAU - Chen, Yunxi
AU  - Chen Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
FAU - Pei, Linguo
AU  - Pei L
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
FAU - Luo, Daji
AU  - Luo D
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
FAU - Fan, Guanlan
AU  - Fan G
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
FAU - Luo, Mengcheng
AU  - Luo M
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
FAU - Xu, Dan
AU  - Xu D
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, 
      Wuhan, China.
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Steroidogenic Factor 1)
RN  - 0 (Steroids)
RN  - 0 (steroidogenic factor 1, rat)
RN  - 4TI98Z838E (Estradiol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Dexamethasone/blood/*toxicity
MH  - Estradiol/blood
MH  - Female
MH  - Fetal Blood/chemistry
MH  - Insulin-Like Growth Factor I/analysis
MH  - Male
MH  - Mitochondria/pathology
MH  - Ovary/chemistry/*drug effects/*embryology
MH  - Pedigree
MH  - Phenotype
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Wistar
MH  - Reproduction/drug effects
MH  - Specific Pathogen-Free Organisms
MH  - Steroidogenic Factor 1/analysis
MH  - Steroids/biosynthesis
EDAT- 2018/01/26 06:00
MHDA- 2018/11/06 06:00
CRDT- 2018/01/26 06:00
PHST- 2018/01/12 00:00 [received]
PHST- 2018/01/12 00:00 [accepted]
PHST- 2018/01/26 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2018/01/26 06:00 [entrez]
AID - 4822184 [pii]
AID - 10.1210/en.2018-00044 [doi]
PST - ppublish
SO  - Endocrinology. 2018 Mar 1;159(3):1401-1415. doi: 10.1210/en.2018-00044.