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Do maternal glucocorticoids transmit the programming effects of maternal stress to the fetus?

Research output: Contribution to conferencePoster

Original languageEnglish
Publication statusUnpublished - 2019
EventBritish Neuroscience Association Festival of Neuroscience 2019 - Dublin, Ireland
Duration: 14 Apr 201917 Apr 2019
http://meetings.bna.org.uk/bna2019/

Conference

ConferenceBritish Neuroscience Association Festival of Neuroscience 2019
CountryIreland
CityDublin
Period14/04/1917/04/19
Internet address

Abstract

Despite attenuated hypothalamo-pituitary-adrenal (HPA) axis responses to acute stress in pregnancy, chronic maternal social stress still exerts negative programming effects on the offspring. The mechanisms by which this occurs remains unclear, but excess maternal glucocorticoid transfer to the fetus could play a possible role. Local concentrations of glucocorticoids are modulated by 11β-hydroxysteroid dehydrogenase (11βHSD) enzymes. In the placenta, 11βHSD2 converts corticosterone (CORT) into the inactive metabolite 11-dehydrocorticosterone (11-DHC), regulating glucocorticoid transfer across the maternal-fetal interface; whilst in the brain, 11βHSD1 converts 11-DHC
to CORT, regulating local glucocorticoid synthesis.
Pregnant rats were exposed to 10min social stress/day via the resident-intruder paradigm, from day 16-20 of pregnancy. Rats were killed following the final bout of stress and blood/tissues collected. Concentrations of CORT and 11-DHC in the maternal and fetal plasma, placenta, fetal brain and liver were quantified using liquid chromatography-mass spectrometry. In situ hybridisation was performed to quantify mRNA expression for 11βHSD2 and glucocorticoid receptor (GR) in the placenta, and 11βHSD1 in the fetal brain. Data were analysed by two-way
ANOVA.
Plasma corticosterone concentrations were 3.7-fold greater in the stressed dams compared to controls. Maternal stress significantly increased circulating corticosterone concentrations in the female fetuses (1.3-fold), but not in the
males. Similar changes were observed for plasma 11-DHC concentrations. CORT concentrations were significantly greater in the liver of both male (1.4-fold) and female fetuses (1.3-fold) following maternal stress; however no changes were detected in the fetal brain. Corticosterone concentrations and 11βHSD2 mRNA expression were significantly greater in male, but not female placentae, from stressed dams compared with controls; with no changes in placental GR mRNA expression in either sex. 11βHSD1 mRNA expression was greater only in the female fetal hippocampus after stress.
In conclusion, although repeated social stress activates the maternal HPA axis, the placental barrier appears intact, especially in the males, and the direct transfer of corticosterone from the maternal to fetal circulation is minimal.
However, some changes in corticosterone metabolism still occur in the fetal liver and fetal brain. The data suggest that maternal glucocorticoids could exert effects on fetal glucocorticoid metabolism, but probably in an indirect, and
sex-dependent manner.

Event

British Neuroscience Association Festival of Neuroscience 2019

14/04/1917/04/19

Dublin, Ireland

Event: Conference

ID: 84253470