Foetal and placental 11 β‐HSD 2: a hub for developmental programming
Abstract
Foetal growth restriction (FGR), reflective of an adverse intrauterine environment, confers a significantly increased risk of perinatal mortality and morbidity. In addition, low birthweight associates with adult diseases including hypertension, metabolic dysfunction and behavioural disorders. A key mechanism underlying FGR is exposure of the foetus to glucocorticoids which, while critical for foetal development, in excess can reduce foetal growth and permanently alter organ structure and function, predisposing to disease in later life. Foetal glucocorticoid exposure is regulated, at least in part, by the enzyme 11 β‐hydroxysteroid dehydrogenase type 2 (11 β‐HSD 2), which catalyses the intracellular inactivation of glucocorticoids. This enzyme is highly expressed within the placenta at the maternal–foetal interface, limiting the passage of glucocorticoids to the foetus. Expression of 11 β‐HSD 2 is also high in foetal tissues, particularly within the developing central nervous system. Down‐regulation or genetic deficiency of placental 11 β‐HSD 2 is associated with significant reductions in foetal growth and birth weight, and programmed outcomes in adulthood. To unravel the direct significance of 11 β‐HSD 2 for developmental programming, placental function, neurodevelopment and adult behaviour have been extensively investigated in a mouse knockout of 11 β‐HSD 2. This review highlights the evidence obtained from this mouse model for a critical role of feto‐placental 11 β‐HSD 2 in determining the adverse programming outcomes.
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Resultant exposure to elevated levels of cortisol may contribute to developmental programming of the fetal hypothalamic-pituitary-adrenal axis and other organ systems.
“Resultant exposure to elevated levels of cortisol may contribute to developmental programming of the fetal hypothalamic-pituitary-adrenal axis and other organ systems (127, 129, 306).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [129]
The same stresses may compromise the protective, barrier functions of the placenta, allowing exposure of the embryo/fetus to abnormally high levels of maternal glucocorticoids, drugs (both therapeutic and recreational), xenobiotics and pathogens.
“Secondly, the same stresses may compromise the protective, barrier functions of the placenta, allowing exposure of the embryo/fetus to abnormally high levels of maternal glucocorticoids, drugs (both therapeutic and recreational), xenobiotics and pathogens (129).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [129]
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Placental Origins of Chronic Disease
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- Authors
- Cottrell, E. C., Seckl, J. R., Holmes, M. C., & Wyrwoll, C. S.
- Affiliations
- University of Manchester (GB)
- University of Edinburgh (GB)
- The University of Western Australia (AU)
- Corresponding author
- Wyrwoll, C. S.
- Venue
- Acta Physiologica
- Publisher
- Wiley
- Published
- 2013-12-12
- Volume
- 210
- Issue
- 2
- Pages
- 288-295
- ISSN
- 1748-1708 (ISSN-L)
- 1748-1716
- OpenAlex
- W1968311059
- Cited by
- 123
- References
- 61
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 25 · 2020: 8 · 2019: 13 · 2018: 12 · 2017: 11 · 2016: 9 · 2015: 5 · 2014: 1
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Physiologica (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Wellcome Trust (WT079009)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- 11β-hydroxysteroid dehydrogenase type 2, placenta, fetal growth restriction, developmental programming, glucocorticoid exposure, low birth weight, brain development, adult behavior, perinatal mortality
- MeSH terms
- Animals, Female, Fetal Growth Retardation, Fetus, Glucocorticoids, Placenta, Pregnancy, Metabolic Syndrome, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Fetal Development, Mice
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