Epigenetic regulation of the placental HSD11B2 barrier and its role as a critical regulator of fetal development.
"Fetal programming" is a term used to describe how early-life experience influences fetal development and later disease risk. In humans, prenatal stress-induced fetal programming is associated with increased risk of preterm birth, and a heightened risk of metabolic and neurological diseases later in life. A critical determinant of this is the regulation of fetal exposure to glucocorticoids by the placenta. Glucocorticoids are the mediators through which maternal stress influences fetal development. Excessive fetal glucocorticoid exposure during pregnancy results in low birth weight and abnormalities in a number of tissues. The amount of fetal exposure to maternal glucocorticoids depends on the expression of HSD11B2, an enzyme predominantly produced by the syncytiotrophoblast in the placenta. This protects the fetus by converting active glucocorticoids into inactive forms. In this review we examine recent findings regarding placental HSD11B2 that suggest that its epigenetic regulation may mechanistically link maternal stress and long-term health consequences in affected offspring.
Irish Centre for Fetal and Neonatal Translational Research (INFANT); Cork University Maternity Hospital; Cork, Ireland; Department of Obstetrics and Gynaecology; Cork University Maternity Hospital; Cork, Ireland; Department of Anatomy and Neuroscience; Biosciences Institute; University College Cork; Cork, Ireland.
Katie L
KL
Togher
Irish Centre for Fetal and Neonatal Translational Research (INFANT); Cork University Maternity Hospital; Cork, Ireland; Department of Obstetrics and Gynaecology; Cork University Maternity Hospital; Cork, Ireland; Department of Anatomy and Neuroscience; Biosciences Institute; University College Cork; Cork, Ireland.
Katie L
KL
Togher
Department of Nutrition and Dietetics; School of Medicine; Kings College London; London, UK.
Majella M
MM
O'Keeffe
Department of Nutrition and Dietetics; School of Medicine; Kings College London; London, UK.
Majella M
MM
O'Keeffe
Irish Centre for Fetal and Neonatal Translational Research (INFANT); Cork University Maternity Hospital; Cork, Ireland; Department of Obstetrics and Gynaecology; Cork University Maternity Hospital; Cork, Ireland.
Ali S
AS
Khashan
Irish Centre for Fetal and Neonatal Translational Research (INFANT); Cork University Maternity Hospital; Cork, Ireland; Department of Obstetrics and Gynaecology; Cork University Maternity Hospital; Cork, Ireland.
Ali S
AS
Khashan
University of Lincoln; Brayford Pool; Lincoln UK.
Humberto
H
Gutierrez
University of Lincoln; Brayford Pool; Lincoln UK.
Humberto
H
Gutierrez
Irish Centre for Fetal and Neonatal Translational Research (INFANT); Cork University Maternity Hospital; Cork, Ireland; Department of Obstetrics and Gynaecology; Cork University Maternity Hospital; Cork, Ireland.
Louise C
LC
Kenny
Irish Centre for Fetal and Neonatal Translational Research (INFANT); Cork University Maternity Hospital; Cork, Ireland; Department of Obstetrics and Gynaecology; Cork University Maternity Hospital; Cork, Ireland.
Louise C
LC
Kenny
Irish Centre for Fetal and Neonatal Translational Research (INFANT); Cork University Maternity Hospital; Cork, Ireland; Department of Anatomy and Neuroscience; Biosciences Institute; University College Cork; Cork, Ireland.
Gerard W
GW
O'Keeffe
Irish Centre for Fetal and Neonatal Translational Research (INFANT); Cork University Maternity Hospital; Cork, Ireland; Department of Anatomy and Neuroscience; Biosciences Institute; University College Cork; Cork, Ireland.
Gerard W
GW
O'Keeffe
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D047109:Fetal Development; D005315:Fetal Diseases / Q000235:genetics; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000517:prevention & control; D013312:Stress, Physiological
D005938:Glucocorticoids; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human
11β-hydroxysteroid dehydrogenase type-2; epigenetic; fetal outcome; placenta; prenatal stress