PMID- 24029241
OWN - NLM
STAT- MEDLINE
DCOM- 20140108
LR  - 20131021
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 154
IP  - 11
DP  - 2013 Nov
TI  - Effects of antenatal synthetic glucocorticoid on glucocorticoid receptor binding, 
      DNA methylation, and genome-wide mRNA levels in the fetal male hippocampus.
PG  - 4170-81
LID - 10.1210/en.2013-1484 [doi]
AB  - The endogenous glucocorticoid (GC) surge in late gestation plays a vital role in 
      maturation of several organ systems. For this reason, pregnant women at risk of 
      preterm labor are administered synthetic glucocorticoids (sGCs) to promote fetal 
      lung development. Animal studies have shown that fetal sGC exposure can cause 
      life-long changes in endocrine and metabolic function. We have previously shown 
      that antenatal sGC treatment is associated with alterations in global DNA 
      methylation and modifications to the hippocampal methylome and acetylome. In this 
      study, we hypothesized that: 1) there are changes in the transcriptional 
      landscape of the fetal hippocampus in late gestation, associated with the 
      endogenous cortisol surge; 2) fetal sGC exposure alters genome-wide transcription 
      in the hippocampus; and 3) these changes in transcription are associated with 
      modified glucocorticoid receptor (GR) DNA binding and DNA methylation. sGC was 
      administered as 2 courses on gestational days (GD) 40, 41, 50, and 51, and the 
      hippocampi of fetal guinea pigs were examined before (GD52) and after (GD65) the 
      endogenous cortisol surge (Term  approximately GD67). We also analyzed fetal hippocampi 24 
      hours and 14 days following maternal sGC injections (n = 3-4/group). Genome-wide 
      modification of transcription and GR DNA binding occurred in late gestation, in 
      parallel with the normal GC surge. Further, sGC exposure had a substantial impact 
      on the hippocampal transcriptome, GR-DNA binding, and DNA methylation at 24 hours 
      and 14 days following the final sGC treatment. These data support the hypothesis 
      that GC exposure in late gestation plays a significant role in modifying the 
      transcriptional and epigenetic landscape of the developing fetal hippocampus and 
      that substantial effects are evident for at least 2 weeks after sGC exposure.
FAU - Crudo, Ariann
AU  - Crudo A
AD  - Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, 
      Ontario, Canada M5S 1A8. Stephen.Matthews@utoronto.ca.
FAU - Petropoulos, Sophie
AU  - Petropoulos S
FAU - Suderman, Matthew
AU  - Suderman M
FAU - Moisiadis, Vasilis G
AU  - Moisiadis VG
FAU - Kostaki, Alisa
AU  - Kostaki A
FAU - Hallett, Michael
AU  - Hallett M
FAU - Szyf, Moshe
AU  - Szyf M
FAU - Matthews, Stephen G
AU  - Matthews SG
LA  - eng
GR  - MOP-126166/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130912
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Glucocorticoids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 9842X06Q6M (Betamethasone)
SB  - IM
MH  - Animals
MH  - Betamethasone/administration & dosage/*pharmacology
MH  - *DNA Methylation
MH  - Female
MH  - Fetal Development/physiology
MH  - Gene Expression Regulation, Developmental/drug effects/physiology
MH  - Genome
MH  - Glucocorticoids/administration & dosage/pharmacology
MH  - Guinea Pigs
MH  - Hippocampus/embryology/*metabolism
MH  - Male
MH  - Pregnancy
MH  - *Protein Binding
MH  - RNA, Messenger/genetics/*metabolism
MH  - Receptors, Glucocorticoid/genetics/*metabolism
MH  - Transcriptome
EDAT- 2013/09/14 06:00
MHDA- 2014/01/09 06:00
CRDT- 2013/09/14 06:00
PHST- 2013/09/14 06:00 [entrez]
PHST- 2013/09/14 06:00 [pubmed]
PHST- 2014/01/09 06:00 [medline]
AID - en.2013-1484 [pii]
AID - 10.1210/en.2013-1484 [doi]
PST - ppublish
SO  - Endocrinology. 2013 Nov;154(11):4170-81. doi: 10.1210/en.2013-1484. Epub 2013 Sep 
      12.