PMID- 36256689
OWN - NLM
STAT- MEDLINE
DCOM- 20221115
LR  - 20221207
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 255
IP  - 3
DP  - 2022 Dec 1
TI  - Maternal glucocorticoids do not directly mediate the effects of maternal social 
      stress on the fetus.
PG  - 143-158
LID - 10.1530/JOE-22-0226 [doi]
AB  - Stress during pregnancy negatively affects the fetus and increases the risk for 
      affective disorders in adulthood. Excess maternal glucocorticoids are thought to 
      mediate fetal programming; however, whether they exert their effects directly or 
      indirectly remains unclear. During pregnancy, protective mechanisms including 
      maternal hypothalamic-pituitary-adrenal (HPA) axis hyporesponsiveness and 
      placental 11beta-hydroxysteroid dehydrogenase (11betaHSD) type 2, which inactivates 
      glucocorticoids, limit mother-to-fetus glucocorticoid transfer. However, whether 
      repeated stress negatively impacts these mechanisms is not known. Pregnant rats 
      were exposed to repeated social stress on gestational days (GD) 16-20 and several 
      aspects of HPA axis and glucocorticoid regulation, including concentrations of 
      glucocorticoids, gene expression for their receptors (Nr3c1, Nr3c2), receptor 
      chaperones (Fkbp51, Fkbp52) and enzymes that control local glucocorticoid 
      availability (Hsd11b1, Hsd11b2), were investigated in the maternal, placental and 
      fetal compartments on GD20. The maternal HPA axis was activated following stress, 
      though the primary driver was vasopressin, rather than corticotropin-releasing 
      hormone. Despite the stress-induced increase in circulating corticosterone in the 
      dams, only a modest increase was detected in the circulation of female fetuses, 
      with no change in the fetal brain of either sex. Moreover, there was no change in 
      the expression of genes that mediate glucocorticoid actions or modulate local 
      concentrations in the fetal brain. In the placenta labyrinth zone, stress 
      increased Hsd11b2 expression only in males and Fkbp51 expression only in females. 
      Our results indicate that any role glucocorticoids play in fetal programming is 
      likely indirect, perhaps through sex-dependent alterations in placental gene 
      expression, rather than exerting effects via direct crossover into the fetal 
      brain.
FAU - Sze, Ying
AU  - Sze Y
AUID- ORCID: 0000-0002-0431-0386
AD  - Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
AD  - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, 
      UK.
FAU - Fernandes, Joana
AU  - Fernandes J
AD  - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, 
      UK.
FAU - Kolodziejczyk, Zofia M
AU  - Kolodziejczyk ZM
AD  - Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
FAU - Brunton, Paula J
AU  - Brunton PJ
AUID- ORCID: 0000-0003-3827-6523
AD  - Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
AD  - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, 
      UK.
AD  - Zhejiang University-University of Edinburgh Institute, International Campus, 
      Haining, Zhejiang, P.R. China.
LA  - eng
GR  - BB/J004332/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221114
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Glucocorticoids)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2)
SB  - IM
MH  - Male
MH  - Female
MH  - Pregnancy
MH  - Animals
MH  - Rats
MH  - *Glucocorticoids/metabolism
MH  - *Hypothalamo-Hypophyseal System/metabolism
MH  - Pituitary-Adrenal System/metabolism
MH  - Placenta/metabolism
MH  - Fetus/metabolism
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics/metabolism
PMC - PMC9716396
OTO - NOTNLM
OT  - glucocorticoids
OT  - placenta
OT  - pregnancy
OT  - prenatal stress
OT  - sex differences
EDAT- 2022/10/19 06:00
MHDA- 2022/11/16 06:00
PMCR- 2022/12/02
CRDT- 2022/10/18 14:08
PHST- 2022/10/04 00:00 [received]
PHST- 2022/10/18 00:00 [accepted]
PHST- 2022/10/19 06:00 [pubmed]
PHST- 2022/11/16 06:00 [medline]
PHST- 2022/10/18 14:08 [entrez]
PHST- 2022/12/02 00:00 [pmc-release]
AID - JOE-22-0226 [pii]
AID - 10.1530/JOE-22-0226 [doi]
PST - epublish
SO  - J Endocrinol. 2022 Nov 14;255(3):143-158. doi: 10.1530/JOE-22-0226. Print 2022 
      Dec 1.