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The Mother or the Fetus? 11β-Hydroxysteroid Dehydrogenase Type 2 Null Mice Provide Evidence for Direct Fetal Programming of Behavior by Endogenous Glucocorticoids
Open accessAbstract
Low birth weight associates with increased susceptibility to adult cardiometabolic and affective disorders spawning the notion of fetal “programming.” Prenatal exposure to excess glucocorticoids may be causal. In support, maternal stress or treatment during pregnancy with dexamethasone (which crosses the placenta) or inhibitors of fetoplacental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), the physiological “barrier” to maternal glucocorticoids, reduces birth weight and programs permanent offspring hypertension, hyperglycemia, and anxiety behaviors. It remains uncertain whether such effects are mediated indirectly via altered maternal function or directly on the fetus and its placenta. To dissect this critical issue, we mated 11β-HSD2 +/− mice such that each pregnant female produces +/+, +/−, and −/− offspring and compared them with offspring of homozygous wild-type and −/− matings. We show that 11β-HSD2 −/− offspring of either +/− or −/− mothers have lower birth weight and exhibit greater anxiety than 11β-HSD2 +/+ littermates. This provides clear evidence for the key role of fetoplacental 11β-HSD2 in prenatal glucocorticoid programming.
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“In addition, deletion of the 11-ßHSD2 gene in mice is associated with fetal growth restriction (261).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [261]
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Metadata
- Authors
- Holmes, M. C., Abrahamsen, C. T., French, K. L., Paterson, J. M., Mullins, J. J., & Seckl, J. R.
- Affiliations
- The Queen's Medical Research Institute (GB)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-04-05
- Volume
- 26
- Issue
- 14
- Pages
- 3840-3844
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6445356
- OpenAlex
- W1971789895
- Cited by
- 200
- References
- 33
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 2 · 2023: 9 · 2022: 4 · 2021: 6 · 2020: 10 · 2019: 8 · 2018: 3 · 2017: 10 · 2016: 16 · 2015: 21 · 2014: 22 · 2013: 9 · 2012: 18
- FWCI
- 10.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (079009)
- Medical Research Council
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- 11β-hydroxysteroid dehydrogenase type 2, fetal programming, antenatal glucocorticoids, anxiety-like behavior, birth weight, placenta, dexamethasone, maternal stress, low birth weight, offspring behavior, glucocorticoid metabolism
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Birth Weight, Female, Fetus, Glucocorticoids, Male, Mice, Inbred C57BL, Mothers, Placenta, Pregnancy, Mineralocorticoid Excess Syndrome, Apparent, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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