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Prenatal stress, glucocorticoids and the programming of adult disease

Elizabeth C Cottrell1, Jonathan R Seckl

  • 1Endocrinology Unit, Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh Edinburgh, Scotland.

Frontiers in Behavioral Neuroscience
|October 15, 2009
PubMed

Insights

Adverse prenatal environments, particularly excess glucocorticoids, can permanently alter offspring physiology, increasing risks for cardio-metabolic and psychiatric disorders later in life. Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) protects against these effects.

Area of Science:

  • Developmental biology
  • Endocrinology
  • Neuroscience

Background:

  • Adverse prenatal environments are linked to adult cardio-metabolic, neuroendocrine, and psychiatric disorders.
  • Prenatal stress or excess glucocorticoids in animal models malprogram offspring, reducing birth weight and increasing disease risk.
  • Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) acts as a barrier to maternal glucocorticoids during fetal development.

Purpose of the Study:

  • To investigate the role of placental 11beta-HSD2 in protecting offspring from adverse prenatal environments.
  • To explore the molecular mechanisms, including epigenetic changes, underlying prenatal programming.
  • To understand how early life glucocorticoid exposure permanently alters glucocorticoid signaling and disease risk.

Main Methods:

  • Review of clinical studies associating prenatal environment with later-life disorders.
  • Analysis of animal model experiments involving prenatal stress or glucocorticoid exposure.
  • Examination of the function and regulation of placental 11beta-HSD2.
  • Investigation of epigenetic modifications and glucocorticoid receptor (GR) expression.

Main Results:

  • Reduced placental 11beta-HSD2 in human pregnancy correlates with lower birth weight and higher blood pressure.
  • Inhibition or knockout of placental 11beta-HSD2 in animal models lowers offspring birth weight by reducing fetal glucose delivery.
  • Prenatal glucocorticoid exposure can lead to epigenetic changes affecting glucocorticoid signaling and increase disease susceptibility.

Conclusions:

  • Placental 11beta-HSD2 is crucial for mitigating the adverse effects of maternal glucocorticoids on fetal development.
  • Early life exposure to excess glucocorticoids can permanently alter glucocorticoid signaling via epigenetic mechanisms, increasing long-term disease risk.
  • Understanding these programming effects is vital for preventing future health issues associated with adverse prenatal conditions.

Keywords:
11β hydroxysteroid dehydrogenase type 2fetal programmingglucocorticoid receptorglucocorticoidsplacentastress

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